what is a research irb

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What Patients Need to Know About Institutional Review Boards

FDA has authority over clinical trials for drug, biologic, and medical device products regulated by the agency. This authority includes studies that are funded by the U.S. Department of Health and Human Services (with joint oversight by FDA and the Office for Human Research Protections), as well as studies that are solely funded by industry or by private parties.

The purpose of an IRB review is to ensure that appropriate steps are taken to protect the rights and welfare of participants as subjects of research. If the risks to participants are found to be too great, the IRB will not approve the research, or it will specify changes that must be made before the research can be done.

As part of their review, IRBs consider participant inclusion and exclusion requirements to be sure that appropriate people have been identified as eligible for the trial. They often look at how and where recruitment for clinical trials will occur.

The IRB also reviews how much money participants receive, and what those payments are for. Paying research subjects to participate in clinical trials is common and is generally considered an acceptable practice. The IRB reviews any payments for participation to make sure they are not coercive and do not have undue influence upon someone’s decision to participate. In contrast to payment for participation, FDA does not consider reimbursement for travel expenses to and from the clinical trial site and associated costs such as airfare, parking, and lodging to raise issues regarding undue influence.  Payment for participation in research should be just and fair. The IRB should review both the amount of payment and the method and timing of the payment to make sure they are appropriate and follow the laws.

IRBs review the adequacy of the informed consent document to ensure that it includes all the elements required by law, and that it is at an appropriate reading level and understandable to study participants.

To help protect the rights and welfare of volunteers and verify the quality and integrity of data submitted for review, FDA performs inspections of clinical trial study sites and anyone involved in the research.

Many groups play important roles in looking out for the safety of research subjects. These groups include FDA, other government agencies, and institutional review boards. There is also monitoring of studies by industry or private sponsors, as well as oversight and reporting by investigators and their staff.

Resources For You

• Institutional Review Boards (IRBs) from HHS.GOV

ORI  Introduction  to RCR: Chapter 3. The Protection of Human Subjects

• risks to subjects are minimized;
• risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result;
• selection of subjects is equitable;
• informed consent will be sought from each prospective subject or the subject’s legally authorized representative;
• informed consent will be appropriately documented;
• when appropriate, the research plan makes adequateprovision for monitoring the data collected to ensure the safety of subjects; and
• when appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.
• respect for persons and their right to make decisions for and about themselves without undue influence or coercion from someone else (the researcher in most cases);
• beneficence or the obligation to maximize benefits and reduce risks to the subject; and
• justice or the obligation to distribute benefits and risks equally without prejudice to particular individuals or groups, such as the mentally disadvantaged or members of a particular race or gender.

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• Institutional Review Board

An institutional review board (IRB) is the institutional entity charged with providing ethical and regulatory oversight of research involving human subjects, typically at the site of the research study. NIH does not require IRB approval before NIH peer review of proposed research; however, the appropriate IRB approval(s) must be in place to implement the research protocol. This review must be conducted by an IRB approved by the HHS Office of Human Subjects Protection; this can include approval by a single or central IRB in the case of multisite studies. Both local and single IRBs must follow the same Federal regulations about human subjects protections provided in 45 CFR 46, Subpart A  and 21 CFR Part 50 (for studies that must also meet Food Drug Administration requirements). IRBs also ensure compliance with relevant local and State regulations.

Each IRB follows its own operational policies. Contact your local IRB to learn how it can work with you to help protect human subjects in your clinical research. IRB staff may be able to offer recommendations on writing the protocol, consent forms, and other documents and on the appropriate training to provide your research staff.

NIH Single Institutional Review Board Policy

NIH Single IRB policy affects multi-site studies involving non-exempt human subjects research funded by NIH and applies to grant applications with due dates on or after January 25, 2018, and R&D contracts in response to solicitations issued on or after January 25, 2018.

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What is an IRB?

IRB is an acronym for Institutional Review Board. The IRB is responsible for the review and approval of all research involving human subjects, as well as scientific validity and ethical review.

What is Research?

In general, research is defined by the Department of Health and Human Services as a “systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge” (45 CFR 46.102(d)).

What is the human subject?

Per Federal regulations (45CFR46.102(f)), a human subject is defined as A living individual about whom an investigator (whether professional or student) conducting research obtains: 1.) Data through intervention or interaction with the individual, or 2.) Identifiable private information.

IRB Policies and Procedures, Manuals, and Other Regulations/Guidance

Find information regarding the IRB’s policies and procedures, manuals, regulations, and guidance.

Where can I find information related to a specific committee?

Each IRB committee has a page with its general description, information.

Find resources related to the committee .

Find the current board member roster for each committee.

Find a detailed listing of meeting deadlines and dates for each committee.

How do I submit a study?

Studies are submitted through our electronic IRB system.

Visit the system, as well as additional information, reference guides, FAQs, log-in guidance, and more.

Is any training required?

Below is a brief overview of the different training requirements.  For more detailed information and instructions, please see our Training webpage .

What are the different review options?

Research applications are reviewed at one of three levels, depending on the level of risk to the human participants and on the federal regulations that define the categories of review. The levels of review are exempt, expedited, and full board review. The determination of what level of review is required is determined by the IRB staff, NOT the researcher.  Categories of research that can be reviewed via exempt or expedited review can be found at the following links:

• Exempt Review Categories
• Expedited Review Categories

To help evaluate the needs for IRB review, please refer to the OHRP decision charts

What are the timelines for review?

IRB approval timeline for minimal risk studies/study submissions:

• Review time for IRB members: 5 business days
• Processing time for IRB Staff: 5 business days

Review timeline for greater than minimal risk studies/study submissions (full board review):

• The study must be submitted before or on the deadline; the study will be reviewed at the meeting associated with the deadline.
• Processing time for IRB staff, after the IRB meeting: 5 business days.

What are the meeting deadlines and dates for submissions to full board?

Check the IRB meeting deadlines and dates.

Users can access both the google calendar for the IRB and/or the detailed listing of deadlines and meeting dates for each committee.  Users are able to subscribe to the IRB google calendar.  A feed of upcoming events including meeting deadlines and dates can also be viewed on the Main IRB webpage.

• Detailed Listing of IRB Deadlines and Meeting Dates

When should a study be terminated?

Click on the following link: Termination Information .

Do classroom projects require IRB review?

Before referring to the material below, please make sure you understand the basic definition of research on human subjects (described above).

Please see the following document for more information on classroom activities:

• Classroom Projects Information

Student-Conducted Research

Find the information regarding Student-Conducted Research.

International Research

International human research refers to research conducted outside the United States using participants from the local community. Such research involving Georgetown University researchers requires review and approval from the GU IRB. Human subjects outside of the United States who participate in research projects conducted or funded by HHS receive the same level of protections as research participants inside the United States.

The approval requirements can be time-consuming, such as translating consent forms, obtaining approval from the international research site, obtaining review and approval by a local ethics review board equivalent to an IRB, etc. Given the additional documentation and review requirements for international research, investigators are strongly encouraged to plan ahead to allow greater time for submitting the protocol application and obtaining IRB approval.

International research applications should identify whether there is a local IRB, Ethics Committee (EC), or government entity that will perform the review in the host country. If a local review has been conducted, a copy of the approval letter/notice should be included in the application. Please consult the International Compilation of Human Research Standards.

Human Research Protection Program and Institutional Review Board

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What is the Institutional Review Board (IRB)?

The Institutional Review Board (IRB) is an administrative body established to protect the rights and welfare of human research subjects recruited to participate in research activities conducted under the auspices of the institution with which it is affiliated.

The IRB is charged with the responsibility of reviewing, prior to its initiation, all research (whether funded or not) involving human participants. The IRB is concerned with protecting the welfare, rights, and privacy of human subjects. The IRB has the authority to approve, exempt, disapprove, monitor, and require modifications in all research activities that fall within its jurisdiction as specified by both the federal regulations and institutional policy. The IRB shall have at least five members of varying backgrounds in order to provide complete and adequate review of human research and its institutional, legal, scientific, and social implications. The Board will also include at least one member who is not affiliated with the institution and one member who is not a scientist. The IRB has several consultants who advise the Board and are periodically involved in protocol review.

Human Research Protection Program, Institutional Review Board B308 Kerr Administration Corvallis, OR 97331-2140 [email protected] Phone: (541) 737-8008

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Division of Research and Innovation A312 Kerr Administration Corvallis, OR  97331-2140 Phone 541-737-3467

Institutional Review Board (IRB)

The IRB has the authority to review, approve, modify or disapprove research protocols submitted by faculty, staff and student investigators at all Mayo Clinic locations. The IRB also aids external institutions as the IRB of record.

The Mayo Clinic Institutional Review Board (IRB) ensures that the rights and well-being of potential research subjects are adequately protected.

The Institutional Review Board is charged with reviewing all studies involving human subjects for compliance with both Mayo Clinic institutional policies and with state, local and federal laws. The IRB also ensures that all studies comply with the ethical principles contained in the Belmont Report, such as respect for people, beneficence and justice.

The Mayo Clinic IRB is made up of four committees comprising at least five members, including Mayo Clinic scientists and nonscientists, and at least one member who is not affiliated with the institution.

In general, an institutional review board is a committee charged by the U.S. government with protecting the rights and welfare of human subjects involved in research. The use of IRBs began in the National Institutes of Health (NIH) when a memorandum issued in 1966 required that investigators receiving funding from public health grants obtain a review of research by a committee of institutional associates.

IRB history

The Mayo Clinic Institutional Review Board began in 1971 as the "Committee on Investigations Involving Human Subjects." From 1972 to 1983, it was known as the "Human Studies Committee." The term "Institutional Review Board" was first used at Mayo Clinic in 1984.

IRB mission

The primary mission of the Mayo Clinic IRB is to ensure the protection of rights, privacy and welfare of all human participants in research programs conducted by Mayo Clinic and associated faculty, professional staff and students.

Coexistent with participant protection is the goal of providing quality service to enhance the conduct of research.

To achieve this goal, the IRB has the authority to review, approve, modify or disapprove research protocols submitted by faculty, staff and student investigators within Mayo Clinic. The IRB review process is guided by federal rules and regulations and is based on the Federal Policy for the Protection of Human Subjects ("Common Rule") , the Belmont Report , and provisions of 45CFR46 — "Protection of Human Subjects" requiring institutions that receive federal funds to have all research involving human participants approved by an IRB .

IRB leadership

The director of the Mayo Clinic IRB is cardiologist R Scott Wright, M.D. , a professor of medicine at Mayo Clinic College of Medicine and Science in Rochester, Minnesota.

Contact the IRB about rights and welfare of human subjects, outside organizations or study team research participation, and for research subjects' applications.

IRB Policy Manual

The policy manual details institutional commitment, membership requirements, review of research, informed consent, recruitment, vulnerable population protection, and more.

Federalwide Assurance (FWA)

The FWA outlines the principles and guidelines that govern Mayo Clinic and its faculty and staff in the protection of the rights and welfare of participants in research.

IRB eSystem

The IRB eSystem is an electronic system used for the submission and management of human subject research applications when the Mayo Clinic IRB serves as the IRB of record for an external institution.

Forms and Tools

Forms and tools are available to assist organizations and study teams that rely on the Mayo Clinic IRB as the IRB of record. A specific form may be recommended or required as a supplement to the IRB 's electronic applications or can be used as a reference.

Definition of Terms

The definition of terms explains legal definitions related to research guidelines and protection of human research subjects, including advocate, emergency treatment and informed consent.

Explore resources for more information about institutional review boards and the protection of human research participants, including the NIH and the Office for Civil Rights.

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The IRB Process

The IRB reviews protocols to ensure appropriate safeguards to protect the rights and welfare of research subjects are in place, according to 45 CFR 46.111 . Federal regulation and institutional operating procedure require that the IRB reviews all the research documents and activities that bear directly on the rights and welfare of the subjects of proposed research. The application or protocol, the consent/assent document(s), tests, surveys, questionnaires and similar measures, and recruitment documents are examples of documents that the IRB reviews.

The IRB process can be broken down into three sections:

Criteria of Approval

Estimated time of review, categories of review.

Before any human subject is involved in research in relationship to this institution, the IRB will give proper consideration to:

The risks to subject are minimized by using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risks and whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes 45 CFR 46.111(a).

It is necessary, therefore, that the IRB assess the validity of the study design in relation to the risks to human subjects. Research that is not scientifically valid exposes research subjects to risks of harm without any possibility of benefit. At BYU the validity of the study design can be accomplished in several ways as outlined in this guidance . 

Other factors that contribute to sound study design: evidence that key personnel are qualified by virtue of training and experience to conduct the research; a clear, well-written protocol that adheres to established principles of the discipline help to establish qualifications of the principal and co-investigators and ensures that the operational aspects of the research have been thought through. 

On the other hand, poorly written protocols that do not demonstrate principles of sound scientific design cannot be approved. Poorly written and designed protocols are the most common reasons for delay in IRB approval.

Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result...

The investigator should proceed by doing the following:

• Assessment of all of the risks associated with the research by identifying all potential harms that could befall a subject and the magnitude and the probability of those harms;
• Ensuring that the appropriate steps have been taken to  minimize the risks  that are identified; and
• Assessment of the possibility and importance of potential benefits to subjects (if any) and to science and society.

The research may be approved by the IRB provided that the benefits outweigh the risks to participants.

Factors that impact risk include:

• the procedure (possible harms);
• the person performing the procedure (training, experience, skill);
• the setting (privacy protections, availability of resuscitation equipment, etc.); and
• the characteristics of the research subject (age, health status).

It is the investigators obligation to explain what will be done, by whom and to whom and where it will be done. Protocols and applications that incompletely describe the study procedures frequently result in requests for more information.

The IRB takes into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons. 

This criterion comes from the ethical principle of justice. No group is unduly burdened or will unfairly benefit from the research. Equitable selection does not mean that all groups are represented in proportion to the population. It means that the selection criteria should be both fair and appropriate to the research question. 

Researchers should be mindful of their study design and assess if it is feasible to include non-English speakers as subjects. The exclusion of non-English speakers must be scientifically supported and not used as a mere inconvenience to the researchers. In some cases, this exclusion is supported when surveys tests, questionnaires are not available in other languages. Some tests are not valid in any other language than English.

The protection of privacy applies to the human subjects in the study and confidentiality is the protection of their data. 

Privacy focuses on the environment where the study will take place, how researchers contact prospective subjects, and how research activities will be realized. Privacy issues depend on the study design and the target population. 

Confidentiality should consider the following : 

• How will access to data be managed? 
• Who should be permitted access to the study documents?
• Who should be allowed to know the identities of those participating as subjects?
• What security plan (password protections, locked cabinets, encryption methods, separate storage of Master Lists from study data) is sufficient to adequately protect the subjects given the inherent sensitivity of the data?

It is important to note that the degree of data security depends on the sensitivity of the data. However, it is good practice to limit identifiable data to research personnel that need to know only. It is also good practice to de-identify data as soon as possible. Investigators should consult with their area data security to create a plan that is up to date and appropriate for the sensitivity of data.

Informed consent will be sought from each prospective subject or the subject’s legally authorized representative, in accordance with, and to the extent required by federal regulations for the protection of human subjects.

Informed consent will be appropriately documented, in accordance with, and to the extent required by federal regulations for the protection of human subjects.

The consent process involves providing the information that a reasonable person would want to know in language that is understandable to the subject. Understandable means at a grade level that they can understand and in their native language.

The IRB has the authority to approve, require modifications to secure approval, and disapprove all research activities overseen and conducted by the organizations. The IRB has the authority to suspend, place restrictions, or terminate approval of research activities that fall within its jurisdiction that are not being conducted in accordance with IRB requirements or that have been associated with serious harm to subjects. The IRB has the authority to observe or have a third party observe the consent process and/or the research if the IRB determines it to be indicated.

The IRB processes the protocols when they are received. Once protocols are logged in iRIS, an email is sent to the PI indicating receipt of the protocol, the designated IRB number, and that it is in the queue for assignment to an IRB staff member. The IRB staff initially screens submissions to determine the completeness and the appropriate type of review.  Submissions may be returned to the study team for changes before the review type is assigned.  The review type may be reassessed at any time during the review process.

There are several factors that will determine the time frame for approval. Depending on risk level and subject populations, attention to appropriate detail, protocols will proceed for exempt and expedited on a continual basis.  Full board reviews are due the 10th of the month to go to the following month’s meeting, typically, the first Thursday of each month. The processing time is dependent on when you are able to respond to the issues.  Please see the below chart for a visual depiction of this process.

Exempt reviews:   If your protocol qualifies for one of the exemption categories, once you address any issues we can provide approval. Please allow 2-3 weeks from submission to approval. 

Expedited review :  The protocol will be sent to one or two IRB members for their review. Once you have addressed any issues we can provide approval. Please allow 4-5 weeks from submission to approval. 

Full Board review :  The protocol will be placed on an IRB meeting agenda. Full board protocols must be ready (all pre-review issues addressed) before it may be placed on an agenda at least 2 weeks before the scheduled meeting. 

Review time is dependent on the Board’s stipulations and the duration for these to be resolved. Please keep in mind that these timelines may be shorter or longer depending on how busy our office is and how quickly you respond to any issues/questions.

Getting Started

What is an Institutional Review Board?

What is an Institutional Review Board (IRB)?

An IRB is a federally required committee that is responsible for overseeing research involving human participants. The IRB is responsible for ensuring that human research participants are not mistreated and that their rights are protected. Our IRB consists of 15 members from various disciplines and backgrounds. The IRB consists of a community member, a non-scientific member, two physicians, and several faculty members from a range of academic backgrounds. We hope that the diverse makeup of our IRB will help provide a fair and thoughtful review of research and its social implications, not just institutional, legal, and scientific concerns. Our IRB is guided by the  Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects Research ,  federal regulations , and institutional policies. Research is reviewed by one of three types of review depending on the nature of the study (See  Types of Review ).

Why is an IRB Necessary?

In the not-so-distant past, the burden of research lay heavily on vulnerable populations such as children, prisoners, the economically disadvantaged, the elderly, those with cognitive impairments, and minority groups. History is filled with examples of individuals and groups targeted for cruel and unethical research and experimentation. Unethical human experimentation such as that conducted during  World War II  and the  Tuskegee Syphilis Study  resulted in the creation of regulatory and ethical safeguards designed to protect the rights and dignity of participants in clinical trials and research studies. IRBs were the ultimate result and are in place to ensure research is conducted ethically and in accordance with federal regulations. IRBs serve as an objective third party, an oversight committee, governed by federal regulations to protect participants and manage risk to those involved in research. 

If you have any other questions, please contact  [email protected] .

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Standards of Evidence for Institutional Review Board Decision-Making

A standard of evidence is a rule or norm pertaining to the type or amount of evidence that is required to prove or support a conclusion. Standards of evidence play an important role in institutional review board (IRB) decision-making, but they are not mentioned in the federal research regulations. In this article, I examine IRB standards of evidence from a normative, epistemological perspective and argue that IRBs should rely on empirical evidence for making decisions, but that other sources of evidence, such as intuition, emotion, and rational reflection, can also play an important role in decision-making, because IRB decisions involve an ethical component which is not reducible to science. I also argue that an IRB should approve a study only if it has clear and convincing evidence that the study meets all the approval criteria and other relevant, ethical considerations; and that for studies which expose healthy volunteers to significant risks, an IRB should require that evidence be more than clear and convincing as a condition for approval. Additional empirical research is needed on how IRBs use evidence to make decisions and how standards of evidence influence IRB decision-making at the individual and group level.

1. Introduction

The Institutional Review Board (IRB) is the focal point of oversight of research with human subjects in the US. 1 Federal regulations require IRB oversight for research with human subjects that is federally funded, is being submitted to the Food and Drug Administration (FDA) to support an application for a regulated product (such as an investigational drug or medical device), or is being submitted to the Environmental Protection Agency (EPA) for consideration in its decision-making concerning pesticide use ( Resnik 2018 ). 2 The regulations define IRB membership, functions, and operations; describe record-keeping and reporting responsibilities; distinguish between full board, expedited, and limited review; and specify criteria for IRB approval of research. The IRB has the authority to approve, disapprove, audit, monitor, oversee, suspend, or terminate research with human subjects ( Food and Drug Administration 2013 ; Environmental Protection Agency 2013 ; Department of Health and Human Services 2017 ). Most academic institutions in the US have at least one IRB or rely on an outside IRB for review of research involving human subjects ( Klitzman 2015 ).

While the federal regulations clearly delineate the role of the IRB in human research oversight, they grant considerable discretion to IRBs concerning the approval of studies. Since the US does not have a national IRB system 3 , local IRBs must decide, by majority vote, whether studies meet the approval criteria, which address key ethical issues, such as minimization of risks, reasonableness of risks, equitable selection of subjects, and informed consent ( Department of Health and Human Services 2017 ). 4 When reviewing a study, individual IRB members must consider the information contained in the application and decide to whether it meets the approval criteria.

Notably absent from the federal research regulations is any mention of standards of evidence that IRB members should use in deciding whether a study meets the approval criteria. 5 A standard of evidence for an IRB would be rule or guideline concerning the type or amount of evidence that is needed to make an approval decision. 6 The regulations leave it to IRBs to decide whether they have sufficient evidence to approve a study. 7

Not including standards of evidence for IRB determinations is an important omission from the federal regulations, because standards of evidence used in making a decision can dramatically impact its outcome. For example, under US criminal law, guilt must be proven beyond reasonable doubt. If the standard of evidence in criminal cases were weaker than beyond reasonable doubt, millions of people would be convicted of crimes who would not have been otherwise.

Standards of evidence can also affect the outcome of IRB deliberations, since the same research proposal might be approved by one IRB but not approved by another if they use different standards of evidence. Numerous studies have documented inconsistency and variability among IRB decisions ( Goldman and Katz 1982 , Hirshon et al. 2002 ; McWilliams et al. 2003 ; Shah et al. 2004 ; Dziak et al. 2005 ; Green et al. 2006 ; Peterson et al. 2012 ). For example, Green et al (2006) , submitted the same observational health services study to 43 different IRBs as part of a collaborative research project. Ten IRBs reviewed the study on an expedited basis 8 ; 31 gave the study full board review; one decided that the study was exempt 9 from IRB review; and one refused to approve the study because it judged it to be too risky ( Green et al. 2006 ).

There are some plausible explanations of inconsistency and variability of IRB review. Chief among these is that IRBs make different decisions about the same study because they interpret and apply key terms in the regulations, such as ‘risk,’ ‘benefit,’ and ‘consent,’ differently ( Edwards et al. 2004 ; Shah et al. 2004 ; Klitzman 2011a ). Other factors that may lead to inconsistent IRB review include differences related to moral and cultural values; scientific knowledge and expertise; and education and training related to human research regulations an oversight ( Silberman and Kahn 2011 ; Resnik 2014 ; Friesen et al. 2019 ). However, another explanation, which cannot be ruled out at present, is that inconsistency and variability occur, in part, because IRBs use different standards of evidence for making decisions.

While inconsistency in IRB decision-making is not inherently unethical and may simply reflect the differences of opinion and interpretation that inevitably arise when human beings deal with complex issues at the intersection of science, law, and ethics ( Edwards et al. 2004 ; Resnik 2014 ; Friesen et al. 2019 ), it may nevertheless be an indicator of more significant problems with IRB decision-making, such as under-protection or overprotection of human research subjects ( Resnik 2014 ). Under-protection is an ethical and compliance 10 problem because it can threaten the rights and welfare of research participants, and overprotection is an ethical problem because it can prevent socially valuable research from moving forward ( Resnik 2014 ; Schneider 2015 ). 11

A second reason for exploring the topic of standards of evidence in IRB decision-making in greater depth is that one might argue that IRB decisions related to risks and benefits should be based largely on empirical evidence 12 rather than on subjective feelings, emotions, or intuitions. 13 In 1979, the authors of the Belmont Report argued that oversight committees should use empirical data to assess risks and benefits systematically ( National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research 1979 ). Numerous other commentators have echoed this view ( Meslin 1990 ; Weijer 2000 ; London 2006 ; Wendler et al. 2005 ; Rid et al 2010 ; Resnik 2018 ). However, several studies have shown that IRB members often make risk/benefit decisions based on feelings, emotions, intuitions, or personal experiences ( Van Luijn et al. 2002 ; Stark 2012 ; Klitzman 2011 , 2015 ). While it is neither possible nor desirable to eliminate subjective elements from IRB decision-making, one might argue that IRB decision-making should be more empirically-based than it currently is ( Pritchard 2011 ; Anderson and DuBois 2012 ; Resnik 2018 ). 14

A third reason for exploring the topic of standards of evidence in IRB decision-making in greater depth is that one might claim that different standards should apply to different decisions. Numerous commentators have argued that it would be ethical to conduct controlled human infection experiments (or challenge studies) on young, healthy adult volunteers to generate data to help accelerate the development of vaccines for acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), the pathogen responsible for the COVID-19 pandemic ( Eyal et al. 2020 ; Schaefer et al. 2020 ; World Health Organization 2020 ). While these experiments could potentially save tens of thousands of lives by reducing the time for vaccine development ( Eyel et al. 2020 ), they have been ethically controversial because they would involve intentionally exposing human subjects to SARS-CoV-2 to test vaccine efficacy. 15 While the mortality and morbidity risks associated with COVID-19 are low for the proposed study population, they are not trivial. According to Salje et al. (2020) , for healthy adults, age 20–29, the risk of dying after becoming infected with SARS-CoV-2 is about 0.007% (or 7 deaths per 10,000 infections). Shah et al. (2020) argue that COVID-19 challenge studies be conducted only if they have demonstrated high social value, such that the knowledge they produce would likely be used by vaccine developers to move vaccines more quickly into Phase III clinical trials. While most people share the moral intuition that evidence for the expected social value for studies like these should be compelling, this raises the question of whether evidence for expected social benefits should be compelling for all studies involving human subjects. Should IRBs demand more evidence for approving a study that exposes human subjects to significant risks without offering them any direct benefits than they would for other types of research, such as minimal risk surveys or sample collection protocols?

For the three reasons elaborated above, I believe that standards of evidence for IRB decision-making is an important topic in human research ethics and oversight that merits further investigation. While there is a growing and informative literature on IRB decision-making, 16 no published articles, to my knowledge, directly address the topic of standards of evidence used by an IRB or its members.

Investigations into IRB standards of evidence can be divided into descriptive and normative queries: 17

• Descriptive (psychological, behavioral) Questions : What standards of evidence do IRBs use? What standards of evidence do IRB members endorse or believe they ought to use? How often do IRBs make decisions based on empirical evidence? How often do IRBs make decisions based on feelings, emotions, or intuitions? How confident are IRB members in the decisions they make? How do IRB members respond to lack of evidence? Are there variations in standards of evidence? What factors are associated with variations? Do IRBs use different standards for different types of research? Do members on the same IRB use different standards? What is the relationship between standards of evidence and group dynamics related to decision-making? Normative (epistemological) Questions : What standards of evidence should IRBs use? Should IRB decision-making be empirically based? Should IRBs rely on emotion, feeling, or intuition in decision-making? How much evidence should IRBs require to make decisions? Should IRBs use different standards of evidence for different types of research?

In this article, I will focus on normative 18 questions concerning standards of evidence for IRB review. Hopefully, my normative analysis will provide some impetus and insight for investigating the descriptive 19 questions empirically. I will defend two main points: 1) IRBs should, for the most part, rely on empirical evidence when approving studies, but other sources of evidence, such as intuition, emotion, or rational reflection, can also play an important role in these determinations; 2) IRBs should use the clear and convincing evidence standard for making approval decisions, except when the study under review will expose healthy volunteers to significant risks, in which case they should approve the study only if evidence is more than clear and convincing.

2. Evidence and IRB Decision-Making

While an IRB is not a court of law, the legal analogy may be useful for thinking about evidence and IRB decision-making. 20 Burden of proof is an essential concept in litigation and jurisprudence. In US criminal law, for example, the prosecution must produce evidence that shows the defendant committed the crime(s) he or she is charged with, and the defense only needs to raise reasonable doubts about the prosecution’s case. The trier of fact, in most cases a jury, must decide whether the prosecution has proven its case beyond a reasonable doubt. In the IRB setting, the investigator has the burden of proof because he or she must produce (or submit) evidence to convince the IRB to approve his or her study. Although the investigator does not have an adversary in the IRB room, IRB members may ask the investigator questions about his or her study and request the investigator to provide additional information if his or her application is incomplete or not adequately documented.

Most of the evidence that IRBs consider consists of information directly related to regulatory and ethical issues ( Stark 2012 ). In the US, IRBs make approval decisions based on criteria stated in the federal regulations. The criteria stipulate necessary conditions for approval; that is, an IRB should not approve 21 a study unless it determines that it meets all the criteria. The criteria require that: 1) risks to subjects are minimized; 2) risks to subjects are reasonable in relation to anticipated benefits to subjects or society; 3) selection of subjects is equitable; 4) informed consent will be sought from prospective subjects or appropriately waived; 5) informed consent will be appropriately documented or appropriately waived; 6) data will be monitored to ensure the safety of subjects (when appropriate); 7) privacy and confidentiality will be protected (when appropriate); and 8) additional safeguards are in place to protect vulnerable subjects ( Department of Health and Human Services 2017 ). 22

Since the regulations do not cover every issue that may impact the rights or welfare of human subjects, most IRBs go beyond their regulatory mandate 23 and apply ethical guidelines, such as the Belmont Report ’s principles 24 , to their decisions ( Emanuel et al. 2000 ; Klitzman 2015 ; Resnik 2018 ). For example, many IRBs require researchers to protect third parties, such as family members or communities, from research risks, even though the regulations do not address risks to third parties ( Resnik and Sharp 2006 ; Shah et al. 2018 ).

Investigators typically submit several documents to IRBs, including: the research protocol, consent form(s), investigators’ curriculum vitae, advertisements, survey instruments (for survey research), investigator’s brochure (for drug or device research), and approvals from other institutional committees, such as scientific review, radiation safety review, and conflict of interest review.

Most of the information needed to decide whether to approve a study will be contained in the protocol and consent form. A protocol 25 usually includes information about previous research on the topic; the rationale for the current study; the research design, methods, procedures, test, interventions, and outcome measures or endpoints; study timelines; statistical considerations, such as sample size and statistical tests; inclusion and exclusion criteria for participating in the research; planned enrollment size; risks of the research and safety measures; benefits of the research; processes for recruitment, enrollment, and consent; protections for privacy and confidentiality; considerations related to vulnerable subjects: children, fetuses 26 , mentally disabled adults; withdrawal of participants; and payments to participants.

Consent forms 27 summarize information about the study contained in the protocol and include additional information that a reasonable person would want to know, including information about the research subject’s legal rights. The US federal regulations specify nine types of information that consent documents must contain and nine types of information that they should contain, if appropriate ( Department of Health and Human Services 2017 ). Consent forms should be written in language that is understandable to the subject and should not include any statements that require participants to waive their legal rights ( Department of Health and Human Services 2017 ).

Before the meeting, IRB members read the documents submitted by the investigator. During the meeting, IRB members review and discuss the research. Most IRBs use a primary reviewer system. The primary reviewer summarizes the study for other IRB members, identifies regulatory or ethical problems or concerns, and makes recommendations. The IRB may also ask the investigator some questions about his or her study, if the investigator has been invited to the meeting ( Klitzman 2015 ).

In addition to the information provided by the investigator, an IRB may consider other types of information relevant to its decision, such as approvals from other committees, including the radiation safety committee, scientific review committee, and conflict of interest committee. An IRB may also consider information pertaining to local laws, values, and traditions, and the needs, interests and concerns of the population or community being studied. Often, IRBs rely on community members on the board to provide them with information about the local population or community. IRBs may rely on scientific members to provide the board with information pertaining to the scientific merits of a study, and physician, nurse, or pharmacist member to provide the board with information concerning medical risks and benefits. If an IRB requires additional information, it may consult with an expert in the subject matter ( Stark 2012 ). 28

IRB members must consider and process all the types of information mentioned above when deciding whether to approve a proposed study. If the IRB does not approve a study, it may require the investigator to revise the protocol, consent form, or other documents as a condition for obtaining approval.

3. How Do IRBs Make Decisions?

As mentioned earlier, there is a growing literature that attempts to peer inside the “black box” of IRB decision-making. 29 Robert Klitzman, for example, has published valuable studies of how IRBs make decisions about consent forms, undue influence, social risk, and scientific design ( Klitzman 2012a , b ; 2013a , b , c , d ; 2014 ; 2015 ). Klitzman has also published studies of the social dynamics involved in IRB decision-making, such as interactions between the chair and IRB members, contributions of community members, and how IRBs deal with conflicts of interest ( Klitzman 2011a , b ; 2012b ; 2015 ). Other noteworthy research includes Pritchard’s philosophical reflections and informed observations 30 on IRB decision-making (2011), Tait et al.’s study of how IRB members make judgments concerning the decision-making capacity of prospective research participants; Stark’s (2012) ethnography of how IRB members interact with each other and the larger society; Clapp et al.’s (2017) analysis of IRB decision letters to investigators; and Grinnell et al.’s (2017) study of IRB members’ confidence pertaining to risk assessments.

While these and other empirical studies have shed a great deal of light on IRB decision-making, they have not focused on how standards of evidence affect IRB judgment and decision-making. To be sure, several studies (e.g. Van Luijn et al. 2002 ; Stark 2012 ; Klitzman 2015 ) have addressed the use of empirical evidence in IRB decision-making, but these studies have not focused on how reliance on empirical evidence functions as a normative standard in IRB decision-making or impacts the thinking of IRB members. How often do IRB members use empirical evidence in making decisions? Do they believe that they should use empirical evidence? How do IRB members incorporate non-empirical evidence, such feelings or intuitions, into their decision-making? How much evidence do IRB members require to make approval decisions? These are the types of psychological and sociological questions that an empirically-oriented investigation of standards of evidence should address.

As stated earlier, the questions I seek to address in this article are normative and epistemological, not descriptive and psychological or sociological. I am interested in what sorts of standards of evidence IRB members ought to use. To make some headway into answering these questions, it will be useful to says a few words about standards of evidence.

4. What Are Standards of Evidence?

A standard of evidence is a rule (or norm) pertaining to the type (or quality) or amount (or quantity) of evidence that is required to prove a conclusion ( Chisholm 1989 ). 31 Logically speaking, we can view each item of evidence as a premise in an inductive or deductive argument. Evidence in an inductive argument can show that a conclusion is highly probable, but it cannot show that a conclusion is certain; certainty can only be achieved by means of a valid, deductive argument ( Copi et al. 2013 ). 32 For example, suppose I flip a coin 10 times and it comes up heads 10 times. I might inductively conclude, based on this evidence, that the coin is biased in favor of heads. I cannot prove this conclusion with certainty, however, because the coin could come up tails 10 times if I flip it another 10 times. 33 A standard of evidence could tell me how many times I must flip the coin to be justified in concluding that it is (or is not) biased ( Goldman 1986 ; Giere et al. 2005 ). A standard of evidence could also tell me what type of evidence I may consider in deciding whether the coin is biased. For example, I could ask a metallurgist to examine the coin to determine whether it is heavier on one side. A standard of evidence could tell me whether I should rely on the metallurgist’s expert opinion to decide whether the coin is biased.

4.1. Legal Standards of Evidence

There are well-developed standards of evidence in the law, science, and medicine. In the law, there are many different standards of evidence that apply to different legal decisions ( Loevinger 1992 ). Three commonly used standards pertaining to the amount of evidence needed to accept a conclusion are (in increasing order of stringency): preponderance of evidence, clear and convincing evidence, and beyond reasonable doubt ( Rothstein et al. 2011 ). The preponderance of evidence standard means that the evidence shows that the conclusion (e.g. a defendant is at fault for negligence) is more likely true than not. Preponderance of evidence is used in civil lawsuits, such as contracts and torts, in which only money is at stake. In civil litigation that may involve restrictions of liberties (such as cases involving restraining orders, child custody, or involuntary commitment), courts use a stronger standard of evidence known as clear and convincing evidence . Evidence is clear and convincing if it shows that the conclusion is substantially more likely true than not. The beyond reasonable doubt standard is used in criminal law. For evidence to meet this standard, it must be so convincing that a reasonable person would doubt that the conclusion that the defendant is guilty ( Rothstein et al. 2011 ).

One could, in theory, formulate these standards quantitatively in terms of probabilities. For example, preponderance of evidence would be probability > 50%; clear and convincing evidence, probability ≥ 75% and beyond reasonable doubt, probability ≥ 95% ( Weinstein and Dewsbury 2006 ). However, viewing legal standards of evidence as quantitative is misleading because these standards are used to guide laypeople (e.g. judges and jurors) in decision-making, and laypeople may not have a firm grasp of the meaning of probability as it applies to legal cases. Accordingly, these standards of evidence should be understood as qualitative, not quantitative.

The law also includes standards of evidence concerning the type of evidence that may be used to prove a conclusion. These standards, known as rules of evidence, come into play when judges decide whether to admit evidence into court. Some of these rules address the admissibility of hearsay evidence, expert testimony, character evidence, confessions, testimony by spouses, and evidence that may be unfairly prejudicial or misleading ( Loevinger 1992 ). The law also has rules concerning the burden of proof, but I will not characterize these rules as standards of evidence because they address the obligations of parties to produce evidence, not the standards that evidence must meet. 34

Although legal evidence is not nearly as objective or rigorous as scientific evidence, it is, for the most part, empirical, because it is based on the testimony of witnesses who have observed events in the world or experts who have special knowledge that is derived from scientific methods ( Loevinger 1992 ). Business, medical, law enforcement, or other documents that record observations are also frequently used as sources of evidence ( Rothstein et al. 2011 ).

4.2. Scientific Standard of Evidence

Science has many different standards of evidence, depending on the type of discipline (e.g. biology, chemistry, physics, psychology) and the nature of methodology used (e.g. experimental, descriptive, quantitative, qualitative). One thing these standards all have in common is a commitment to empiricism , i.e. the idea that knowledge should be based on observation, testing, and experiment, not on subjective feelings, emotions, intuitions, or impressions ( Kitcher 1993 ; Haack 2003 ; Giere et al. 2005 ). Thus, a general standard of evidence common to all sciences is that evidence used to support hypotheses or theories should be empirical. 35

Scientists use a variety of quantitative methods to evaluate empirical evidence ( Giere et al. 2005 ). Frequentist statistical testing involves sampling data from populations and using a statistical test decide whether to reject the null hypothesis, i.e. the hypothesis that there is no difference between sampled populations with respect to a variable of interest. The p-value (or significance value) for a statistical test is the probability that the test result is due to chance. A commonly used standard for rejecting the null hypothesis is a p-value of 0.05 or less. For example, suppose that an investigator conducts a randomized, controlled trial (RCT) that compares a new drug to a placebo and uses a Chi-square test to analyze the data. If the Chi-square test shows that the new drug is three times more effective than the placebo, with p = 0.05, the investigator could reject the null hypothesis and conclude that the drug is more effective than the placebo ( Weiss 2011 ).

Despite the widespread popularity of the frequentist statistical testing, many scientists use other methods of data analysis. The reasons for this are twofold. First, in many areas of science frequentist statistical testing is neither practical nor helpful, due to the nature of the phenomena under investigation, the goals of research, or other factors. The hypothesis that the SARS-CoV-2 virus originated in horseshoe bats, for example, cannot be proven or disproven using frequentist statistical testing methods, because this is a single, historical event that is not likely to be repeated anytime soon. Scientists have obtained evidence relevant to this hypothesis by comparing the genome of SARS-CoV-2 to genomes of coronaviruses found in horseshoe bats ( Lau et al 2020 ).

Second, many statisticians and scientists are critical of the use of p ≤ 0.05 as a criterion for hypothesis acceptance, because 1) 0.05 is an arbitrary number that may not accurately reflect the total weight of evidence for or against a hypothesis; 2) with a large enough dataset it is almost always possible to find statistically significant but scientifically meaningless associations; and 3) using 0.05 as standard for publication may discourage researchers from publishing interesting or important results where p > 0.05 and may encourage researchers to manipulate data analysis to obtain desirable p-values (a.k.a. “p-hacking”), which can lead to the publication of irreproducible results ( Amrhein et al. 2019 ). 36

In the last few decades, the Bayesian approach to evaluating evidence has emerged as an alternative to frequentist statistical testing. The Bayesian approach is based Bayes’ theorem, which is a formula for calculating conditional probabilities based information about other probabilities. For Bayesians, the probability of a hypothesis, given the evidence, is a function of the prior probability of evidence, given the hypothesis; the prior probability of the hypothesis; and the prior probability of the evidence ( Howson and Urbach 1989 ). 37 A hypothesis (H1) is compared not to the null hypothesis but to an alternate hypothesis (H2), so evidence will affect the probability of H1 relative to H2. For example, suppose that H1 is “SARS-CoV-2 originated in horseshoe bats” and that H2 is “SARS-CoV-2 originated human beings.” Suppose the evidence is that the SARS-CoV-2 genome has a 96% homology to coronavirus genomes found in the horseshoe bat and 75% homology to the human coronavirus genomes ( Lau et al. 2020 ). One could use Bayes’ formula to calculate the probability of these alternative hypotheses, given the evidence and prior probabilities. Bayesians hold that scientists should update probabilities as they acquire new evidence, so that the probability of a hypothesis may change in response to the data ( Howson and Urbach 1989 ).

Although many scientists have adopted the Bayesian approach to hypothesis testing, a well-known shortcoming of this method is that it relies on estimates of prior probabilities, which may not be known ( Earman 1992 ). Many Bayesians hold that one can make subjective estimates (or educated guess) of unknown prior probabilities, but subjective estimates may be biased, so that final results could also be biased. For example, if one estimated that the prior probability of H1 was only 10%, the evidence might not increase its probability to more than 50%. The Bayesian reply to this objection is that repeated testing will eliminate biased estimates so that, in the long run, probabilities will reflect the evidence, not biases ( Howson and Urbach 1989 ).

An entirely different approach to evaluating evidence is to supplement quantitative methods of data assessment with qualitative, epistemic criteria when deciding whether to accept or reject a hypothesis or theory ( Kuhn 1977 ; Thagard 1988 ; Kitcher 1993 ; Haack 2004; Giere et al. 2005 ). One reason for using this approach is that science often involves the development of complex causal theories and models, which cannot be tested using frequentist or Bayesian methods ( Giere et al. 2005 ). For example, the hypothesis that childhood exposure to allergens and pathogens can protect against asthma, allergies, and autoimmune diseases by teaching the immune system to distinguish between self and non-self, also known as the hygiene hypothesis, is a general, causal theory that cannot be proven or disproven using frequentist or Bayesian testing methods. To evaluate this theory, scientists must weigh and consider evidence from a variety of disciplines, including epidemiology, immunology, microbiology, pulmonology, and rheumatology ( Stiemsma et al. 2015 ). Some of the epistemic criteria that scientists use to evaluate theories and models include: testability (is the theory testable?), empirical adequacy (does theory fit the data well?), simplicity (is the theory simple or parsimonious?), precision (does the theory make precise predictions?), generality (is the theory widely applicable?), robustness (is the theory supported by independent sources of evidence?), fruitfulness (does the theory open up new areas of inquiry?), and explanatory power (does the theory unify disparate phenomena?) ( Kuhn 1977 ; Thagard 1988 ; Kitcher 1993 ). Scientists could use these criteria when deciding whether to accept, reject, or modify the hygiene hypothesis.

4.3. Medical Standards of Evidence

Finally, we should consider medical standards of evidence. Since the time of Hippocrates (460–370 BCE), medicine has aspired to be an empirical and scientific discipline. Although Hippocratic medicine was more scientific than the superstitious practices it replaced, it was for the most part observational, not experimental. During the Scientific Revolution, physicians realized that medicine did not have the degree of rigor found in the “hard” sciences such as physics, chemistry, and astronomy. Responding to the need to set medicine on a scientific footing, William Harvey (1578–1657) and Claude Bernard (1813–1878) pioneered the use of experimental and quantitative methods in medicine ( Porter 1998 ). However, physicians have not always lived up to this high standard. Treatment recommendations have often been based on traditional ways practicing medicine learned during medical education and training, clinical observations gained during medical practice, and folk wisdom, not on scientific evidence derived from well-designed experiments ( Sackett et al. 2000 ).

In the 1990s, physicians who were concerned that treatment recommendations in medicine were often not based on good evidence developed an approach to medical decision-making known as evidence-based medicine (EBM). According to EBM, medical decisions should be based on the best available evidence ( Sackett 1989 ; Sackett et al. 2000 ; Burns et al. 2011 ). One of the pioneers of EBM, David Sackett (1989) , distinguished between five levels of evidence (listed from best to worst): evidence from large RCTs with clear results, followed by: smaller RCTs with unclear results and cohort and case-control studies; historical cohort or case-control studies; and case series or studies with no controls ( Sackett 1989 ). Others have modified Sackett’s approach to levels of evidence. According to the Oxford Centre for Evidence-Based Medicine, the highest level of evidence comes from systematic reviews of RCTs, followed by: RCTs or observational studies with dramatic effects; non-randomized controlled cohort studies; case series, case control, or historically controlled studies; and mechanism-based reasoning ( Oxford Center for Evidence Based Medicine, Levels of Evidence Working Group 2011 ). Although EBM has become highly influential since it was conceived in the 1990s, physicians have been slow to adopt evidence-based practices for political, social, and economic reasons ( Patashnik et al. 2017 ).

5. IRB Standards of Evidence

5.1. type of evidence.

We now turn to question that is the central focus of this paper: what standards of evidence should IRBs use? Let’s begin with the question concerning standards related to the type of evidence. As noted earlier, several commentators have argued that IRB decisions should be based on empirical evidence, rather than intuition, feeling, or emotion ( Meslin 1990 ; Rid et al 2010 ; Pritchard 2011 ; Anderson and DuBois 2012 ). There are several arguments for this position. First, many IRB decisions are grounded in descriptive claims relating to soundness of research design, feasibility of studies, minimization of risks, expected risks and benefits, adequacy of consent, and the effectiveness of the consent process and confidentiality protections. Since these are descriptive, factual claims, they should be supported by empirical evidence. For example, whether an experimental drug is likely to produce anemia as a side-effect is a descriptive statement best answered by empirical evidence, as is the question of whether iron supplements can minimize this risk. Whether a consent form would be understandable by an adult with a 7 th grade reading level is a question that can be answered empirically, as is the question of the mental capacity needed to consent to study participation.

Second, relying on empirical evidence in decision-making can help reduce inconsistency and variability by making IRB determinations more objective and rational ( Anderson and DuBois 2012 ). For example, if IRBs use empirical evidence to estimate the risks of skin biopsies less than 3cm in diameter, they are less likely to disagree about classifying these procedures as minimal risk or more than minimal risk.

Third, relying on empirical evidence can enhance the accountability and transparency of IRB decisions by allowing IRBs to cite clear, objective reasons for their decisions in communications with investigators and oversight agencies. Various commentators have faulted IRBs for their lack of accountability and transparency (see Schrag 2010 and Schneider 2015 , for example), and making IRB decisions more empirically-based could help dispel this criticism.

While I find these arguments to be compelling, they have important limitations because IRB decision-making synthesizes scientific and ethical considerations. IRB decision-making includes a descriptive, factual component as well as a normative, ethical component ( Resnik 2017 ). While empirical evidence can be extremely useful in addressing the scientific aspects of IRB decision-making, it cannot settle the ethical dilemmas related to those decisions because ethics is not reducible to empirical science. To be sure, empirical research can inform ethical decision-making by helping us understand the consequences and feasibility of different choices and the social practices that generate and reinforce value commitments, but it does not provide us with a hegemonic source of moral value ( Kon 2009 ). To make ethical decisions, we must not only consider the facts and circumstances related to our choices, but also our moral values, principles, or frameworks, which may be derived, at least in part, from intuition, emotion, culture, religion, or rational reflection ( Audi 2005 ; Beauchamp and Childress 2012 ; Greene 2013 ; Resnik 2017 ). 38

Consider, for example, IRB decisions related to risks and prospective benefits. Claims about risks and prospective benefits are predictions about what is likely to happen, based on empirical evidence. Risk is a function of the probability and magnitude (or severity) of harm, and prospective a benefit is a function of the probability and magnitude (or worth) of the benefit ( Levine 1988 ; Wendler et al. 2005 ; Rid et al. 2010 ; Resnik 2018 ). Science can provide us with evidence concerning probabilities, but it cannot tell us how to compare benefits and harms. Concerning the COVID-19 vaccine challenge study mentioned above, empirical evidence can tell us how likely it is that various adverse (or bad) outcomes (such as illness, hospitalization, or death) and desirable (or good) outcomes (such as shortening the length of time for vaccine development) will occur, but it cannot tell us how to decide whether the prospective benefits are worth the risks, i.e. are reasonable or acceptable, given the risks. Risk/benefit decisions have an inherently normative (or value) component that cannot be reduced to descriptive facts ( Shrader-Frechette 1991 ; Hannson 2003 ). 39

Decisions related to consent also involve value judgments. The regulations require that informed consent take place under conditions that minimize the potential for coercion and undue influence ( Department of Health and Human Services 2017 ). IRB members are often concerned that offering prospective subjects too much money for research participation could be coercive or unduly influential ( Largent et al. 2012 ). While empirical research can provide IRB members with evidence of how money affects judgments about research risks and the decision to enroll in research (for review of the evidence, see Largent and Fernandez-Lynch 2017 ), it cannot tell them whether (or when) financial influences on judgment and decision-making constitute coercion or undue influence, because this is a normative/philosophical issue, not an empirical one ( Wertheimer and Miller 2008 ; Millum and Garnett 2019 ). Deciding whether an offer of money constitutes coercion or undue influence depends, in part, on our moral intuitions pertaining to these concepts ( Resnik 2019 ).

I will also assert, but not argue in this paper, that IRB decisions concerning risk minimization, equitable subject selection, privacy and confidentiality protections, and safeguards for vulnerable subjects are similar to judgments about risk/benefit and consent because they involve a value component. In sum, while there are strong arguments that IRBs should rely on empirical evidence to make decisions, other sources of evidence, such as intuition, emotion, culture, or rational reflection, can also play an important role decision-making because IRB decisions are not purely descriptive or factual.

5.2. Amount of Evidence

Concerning the amount of evidence that IRBs need to make a decision, three arguments support using legal standards, as opposed to scientific or medical ones. First, the evidence that the IRB considers in making its determinations may not be completely quantifiable because, as discussed above, it is likely to include value judgments that are not reducible to scientific data or facts. As a result, quantitative methods of assessing evidence, such as those used in science and medicine, may not apply to these determinations. For example, evidence for a statement that “The risks of study X are reasonable in relation to the benefits to subjects or the importance of the knowledge expected to be gained” cannot be assessed using frequentists or Bayesian methods because it involves making a value judgment concerning the comparison of risks and benefits. 40 Likewise, evidence for the statement that “Subjects selection for study X is equitable” cannot be assessed using quantitative methods because it involves values judgments concerning fairness or justice.

Second, even when evidence is quantifiable, the IRB may lack sufficient information to use quantitative methods to assess it, due to lack of published (or publicly available) research on the topic in question or insufficient time or resources to conduct a thorough search of the literature. For example, consider risk/benefit assessment for a Phase I study of a new drug. While preclinical studies on laboratory animals can provide investigators with some evidence concerning the probability that the drug will adverse effects (such as liver toxicity) on human subjects at a particular dose, the evidence is often not strong enough to support reliable estimate of probabilities related to these effects, using frequentists or Bayesian methods. Indeed, the main reason for conducting a Phase I study is to learn more about the risks of the drug in human beings. Animal data can provide some evidence of risk, but it often falls short of the mark, due to differences between animals and humans and other scientific issues ( Kimmelman 2009 ). Furthermore, probability estimates concerning potential benefits of new drugs are usually highly speculative, due to lack of evidence. While Phase I safety trials of new drugs are widely regarded as socially beneficial because they are an essential step in drug testing and development, only about 10–12% of new drugs that enter Phase I testing are ultimately approved by the Food and Drug Administration ( Seiffert 2016 ). Moreover, many of these drugs have marginal benefits because they are intended to treat conditions for which there is already an effective medication ( Goozner 2004 ; Spector 2005 ).

Third, non-scientist members on the IRB may not be trained in quantitative methods of evaluating evidence used in the sciences or medicine. Although scientific members of the IRB may be familiar with these methods and use them in forming their own judgments concerning the approval criteria and conveying their opinions to the board, non-scientists members may not be able to understand these methods of use them appropriately. If we assume that all members of the board should use the same standards for assessing of evidence when making group decisions to avoid irresolvable conflicts and misunderstandings, 41 it follows that the IRB should use legal standards for assessing the amount of evidence, because both scientists and non-scientists can understand and use these standards. Legal standards provide a qualitative, easily understandable way of assessing empirical evidence.

If IRBs should use legal standards for determining the amount of evidence needed to make a decision, which standards should they use: preponderance of evidence, clear and convincing evidence, or beyond reasonable doubt?

Preponderance of evidence would set too low of a standard for IRB decision-making, since it would allow an IRB to approve a study if it is convinced that the evidence shows that it is more likely than not that the study meets the criteria for approval. As noted above, the law uses standards more demanding than preponderance of evidence, such as clear and convincing or beyond reasonable doubt, when the decisions with significant implications for human rights. Since most of the determinations that an IRB makes have significant implications for the rights of research subjects, such as the right to consent to research, the right to privacy, and the right to not be exploited ( Katz 1993 ), an IRB should, following the legal analogy, use a standard of evidence more demanding than preponderance of evidence. An IRB should not approve a study unless it determines that it is highly likely that risks will be minimized, that consent will be sought or appropriately waived, or that confidentiality and privacy will be protected.

While preponderance of evidence would set too low of a standard, beyond reasonable doubt would set too high of a standard, since one can often raise reasonable doubts about IRB determinations, especially those related to the reasonableness of risks ( Grinnell at al. 2017 ). Investigators often do not know, with a high degree of confidence, that their research is likely to benefit participants or contribute significantly to the advancement of knowledge or otherwise benefit society. Most consent documents used in clinical trials include a phrase stating that “you may not benefit,” or some wording to that effect ( Joffe et al. 2001 ). 42 Expected benefits to society often fail to materialize because a study may not achieve its aims and objectives, due to difficulties with recruitment, implementation, or other problems; or because the research results are not applied to practical problems in medicine, public health, or other disciplines. Also, as noted above, physicians have been slow to implement EBM in medical practice, which diminishes the social benefits of medical research.

Since preponderance of evidence sets too low of a bar and beyond reasonable doubt sets too high of a bar, it follows that the clear and convincing evidence standard is the best standard for IRB decision-making, since it is neither too low and nor too high. As discussed previously, the clear and convincing evidence standard applies to civil litigation that involves significant human rights issues, which is certainly the case in IRB decisions. One could argue, therefore, that to adequately protect the rights of human research participants an IRB should approve a study only when it has clear and convincing evidence that the study meets all of the regulatory criteria for approval, as well as other, relevant ethical guidelines, such as the Belmont Report ’s principles.

6. Variations in Standards of Evidence

In this section, will to return to a question I posed earlier: should an IRB require more evidence for some types of research? 43 Recall the proposed COVID-19 vaccine challenge study described earlier. Should an IRB approve this study only if it has more than clear and convincing evidence that the study meets the regulatory approval and other ethical guidelines? One could argue that for a study like this one, an IRB should use a higher standard of evidence than it uses for other studies because so much is at stake for the human participants and the research enterprise. The participants are healthy volunteers who face significant risks, including the risk of serious illness, prolonged hospitalization, or even death. Moreover, they are not expected to derive direct, medical benefits from their participation. 44 The research enterprise also has a great deal at stake because if healthy volunteers die as a result of their participation in the experiment, the public’s trust in the research enterprise in general, and vaccine research in particular, could be significantly eroded ( Resnik 2012 ). While a study like this one could produce significant social benefits by accelerating vaccine development, one might argue that the evidence that the risks of research are reasonable in relation to its expected benefits should be more than clear and convincing. 45 Likewise, evidence for other approval criteria, such as risk minimization, consent, and equitable subject selection, should also be more than clear and convincing.

The idea that an IRB should require more evidence to approve some types of studies may sound unorthodox to some, but it has analogs in the law and in the philosophy of science. As noted above, there are different legal standards of evidence depending on what is at stake: preponderance of evidence is used in civil litigation when only money is at stake, but clear and convincing evidence is used when human rights are impacted. Beyond reasonable doubt is used in criminal law, because a conviction can lead to imprisonment or even death (in some jurisdictions). Since the 1950s, philosophers of science have argued that standards of evidence in research should vary depending on what is at stake ( Douglas 2000 ; Elliott 2017 ). The originator of this idea was Richard Rudner (1953) , who argued that the degree or amount of evidence that is needed to accept a hypothesis should depend on the consequences of mistakenly accepting the hypothesis. We should require more evidence to accept a hypothesis concerning the safety of a new drug, for example, than to accept a hypothesis concerning the mating behavior of North American Mountain Goats, because the consequences of mistakenly accepting the former are potential worse than the consequences of mistakenly accepting the former.

7. Objections and Replies

Before concluding this article, I would like to respond to two objections to my view. The first objection is that my view is too idealistic and may be out of touch with the realities of IRB decision-making. It may be the case the IRBs seldom rely on empirical evidence or that their decisions often fall way short of the clear and convincing standard of evidence. Before proposing a normative standard, we should have a better understanding of how IRBs actually make decisions.

While I agree that a normative framework for making IRB decisions should be informed by descriptive data concerning how IRBs make decisions, it does not follow that one cannot develop normative recommendations independently of descriptive research studies. Normative and descriptive inquiries can proceed concurrently and collaboratively. Indeed, one reason why I have written this paper is to stimulate interest in descriptive, empirical investigations of IRB decision-making. That being said, the primary aim of normative epistemology is to establish ideal standards for forming beliefs and making judgments and decisions. While these standards should provide us with guidance that can improve our belief formation, judgment, and decision-making, these standards should not be so far removed from that they are impossible to fulfill ( Goldman 1986 , 1999).

A second objection to my view is that claiming that IRBs should more evidence for to approve some types of studies than others could lead to excessive variation in IRB decision-making and confusion about standards of evidence. I agree that this could be a problem but I think it can be managed if the higher standard of evidence is rarely used regulatory agencies and academic institutions provide clear guidance for using it.

8. Conclusion

In this article, I have examined IRB standards of evidence from a normative, epistemological perspective. I have argued that IRBs should, for the most part, rely on empirical evidence for making decisions, but that other sources of evidence, such as intuition, emotion, or rational reflection, can also play an important role in decision-making, because IRB decisions involve an ethical (or value) component which is not reducible to science. I have also argued that an IRB should approve a study only if it has clear and convincing evidence that the study meets all the approval criteria and other relevant, ethical guidelines; and that for studies which expose healthy volunteers to significant risks, an IRB should require that evidence be more than clear and convincing as a condition for approval. I believe that my article is the first to explore the topic of IRB standards of evidence from a normative perspective, and I encourage others to investigate this topic, especially from an empirical perspective. Additional research is needed on how IRBs make decisions based upon evidence and how standards of evidence influence IRB decision-making at the level of the individual and the group. Since the federal regulations do not address standards of evidence used in IRB decision-making, oversight agencies, such as OHRP and FDA, may consider providing additional guidance for investigators and IRBs.

Acknowledgments

This research was supported by the Intramural Program of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH). It does not represent the views of the NIEHS, NIH, or US government. I am grateful to Emily Anderson, Ramin Karbasi, Elise Smith and David Wendler for helpful discussions. On November 9, 2020, I presented a version of this paper to the Consortium to Advance Effective Research Ethics Oversight. I am also grateful to members of this audience for helpful comments and discussions.

1 Other countries have institutional structures which are similar to IRBs but go by different names, such as research ethics boards (REBs) or research ethics committees (RECs).

2 In this article, I will cite regulations found in the Common Rule (45 CFR 46), which is accepted by 17 federal agencies. Regulations pertaining to IRBs adopted by the FDA and EPA are virtually identical to the Common Rule with respect to the IRB’s structure, function, and operations.

3 Over half of the nations in Africa have national IRBs or REBs ( Klitzman 2012a ).

4 An advantage of local IRB review is the local IRBs are likely to have better knowledge of the qualifications of investigators, the institutional research environment, and local values and cultural practices than national IRBs ( Moon 2009 ).

5 As far as I know, the federal regulations are not unique in this regard. That is, I know of no major ethical regulation of guideline that discusses standards of evidence for approving human subjects research.

6 It is worth noting that the federal policy on research misconduct includes a standard of evidence. Research misconduct must be proven by preponderance of evidence. The federal policy applies to research funded by federal agencies or conducted to support application to the FDA ( Office of Science and Technology Policy 2000 ).

7 In theory, oversight agencies, such as the Office of Human Research Protections (OHRP) and the FDA, could provide standards of evidence for IRBs by issuing interpretative guidance for applying approval criteria to proposed research. However, these agencies have not done so.

8 The federal regulations allow IRBs to make some decisions on an expedited basis. New studies can be reviewed on an expedited basis if they determined to be no more than minimal risk. Expedited reviews are conducted by the IRB chair or a designated IRB member ( Department of Health and Human Services 2017 ).

9 The federal regulations state that some types of research are exempt from IRB review. Some common exemptions include research involving surveys, interviews, or focus groups, and research on de-identified data or samples ( Department of Health and Human Services 2017 ).

10 The Office of Human Research Protections (OHRP), which oversees research funded by the Department of Health and Human Services, enforces the federal regulations by issuing determination letters to institutions for non-compliance. Institutions must take appropriate steps to comply with the regulations or OHRP may temporarily halt their funding. The FDA oversees research conducted on FDA-regulated products and enforces its regulations by issuing determination letters to IRBs. The FDA can enforce its regulations by withdrawing approval of IRBs that have registered with the agency. The FDA can also enforce its regulations by informing the sponsor that its research cannot be used in FDA decision-making because it is non-compliant ( Resnik 2018 ).

11 In the study by Green et al. (2006) discussed above, it is likely that IRB that did not approve the health services research protocol was being overprotective.

12 By empirical evidence, I mean evidence from observation, testing, or experimentation ( Goldman 1986 ; Chisholm 1989 ).

13 An intuition is a judgment or belief that is formed without conscious awareness of any reasoning process at work ( Resnik 2017 ).

14 I use the term “empirically-based” rather than the more popular term “evidence-based” because evidence could, in theory, come from non-empirical sources, such as intuition, logical proofs, or rational arguments. Evidence in mathematics, for example, comes from logical proofs and mathematical intuitions ( Resnik 2000 ).

15 In October 2020, the UK approved a COVID-19 vaccine human challenge trial to be conducted by Open Orphan, a commercial research organization. The UK government will also fund the study. The study is scheduled to begin in January 2021 ( Callaway 2020 ).

16 I discuss some of this literature below.

17 For more on the relationship between descriptive and normative statements in ethics and epistemology, see Kon (2009) , Goldman (1986 , 1999).

18 By “normative” I also mean “evaluative” or “prescriptive.” A normative claim says what ought to be the case or what we ought to do.

19 By “descriptive” I also mean “factual,” “predictive,” or “explanatory.”

20 Schneider (2015) applies legal concepts to IRB decision-making and argues that IRBs do not adhere to important legal requirements, such as due process and accountability.

21 An IRB must apply the same regulatory criteria to approve new studies, to reapprove (or renew) previously approved studies, and to approve proposed changes (or amendments) to studies ( Department of Health and Human Services 2017 ).

22 I am paraphrasing the regulations. For the exact wording, see Department of Health and Human Services (2017) . I have omitted approval criteria for limited IRB review or broad consent.

23 Whether an IRB should exceed its regulatory mandate is ethically controversial. Some commentators argue that to avoid “mission creep” IRBs should stay within their regulatory mandate and make decisions based only on the approval criteria ( Gunsalus et al. 2006 ; Schrag 2010 ). Others argue that to protect human subjects (and others) from research risks, IRBs sometimes need to make decisions based on rules or guidelines not explicitly stated in the federal regulations ( Emanuel et al. 2000 ; Resnik 2018 ).

24 The Belmont Report’s principles are respect for persons, beneficence, and justice ( National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research 1979 ).

25 Many academic institutions have developed protocol templates. See Council for International Organizations of Medical Sciences (2016) for a detailed list of information to include in a protocol.

26 The federal research regulations include special protections for pregnant women and fetuses in research but do not classify pregnant women as vulnerable subjects ( Department of Health and Human Services 2017 ).

27 Many academic institutions have consent templates. See, for example, Northwestern University Institutional Review Board (2020) .

28 Interesting epistemological and ethical questions arise here concerning the IRB’s reliance on expert testimony, but I will not address them in this paper. See Selinger and Crease (2006) for further discussion of expertise.

29 Anderson and DuBois (2012) argue that IRB decision-making is like a black box because for many years it has been shrouded in secrecy since IRB meetings are confidential and many IRBs are reluctant to allow outside researchers to study their deliberations.

30 Pritchard has been a senior advisor to OHRP since 2004.

31 We could also say that we are justified in believing the conclusion, the evidence ( Goldman 1986 ). A conclusion could be a statement or belief that supports a decision. For example, if an IRB concludes that a study meets all the approval criteria it could decide to approve a study.

32 Deductive arguments are common in the formal sciences, such as mathematics, logic, statistics, and decision theory, but not very common in the natural sciences, medicine, and engineering, because these disciplines obtain knowledge from observation and experiment rather than logical argumentation and proof ( Resnik 2000 ). Since deductive arguments probably play only a minimal role in IRB decision-making, I will focus on inductive arguments in this paper.

33 We could construct a valid, deductive argument using the axioms of probability theory to estimate the probability of flipping a fair coin and getting heads ten times in a row. We assume that the probability of flipping the coin and getting heads is 0.5, and that each coin flip is independent of the other flips. We also know, from probability theory, that the probability of two independent events is the product of their individual probabilities ( Weiss 2011 ). Given these premises, we can conclude, deductively, that the probability of flipping a fair coin and getting heads ten times in a row is: (0.5)(0.5)(0.5)(0.5)(0.5)(0.5)(0.5)(0.5)(0.5)(0.5) = 0.00098.

34 In US criminal cases, the prosecution has the burden of proof. In civil cases, the person bringing the matter before the court (i.e. the plaintiff) has the burden of proof ( Loevinger 1992 ).

35 While there is little dispute that science is an empirical enterprise, non-empirical methods, such as mathematical modeling, logical and mathematical proof, conceptual arguments, and thought experiments have played and continue to play an important role in scientific theorizing and discovery ( Kuhn 1977 ; Haack 2003 ). For example, in 1846 Urbain Le Verrier (1811–77) used information about the perturbations in the orbit of Uranus and mathematical equations from celestial mechanics to predict the position a new planet, later named Neptune. Johann Galle (1812–1910) pointed his telescope at the coordinates provided by Le Verrier and discovered the planet (Pannekoek 2011).

36 These same criticisms would apply to using p-values for statistical significance.

37 The formula is: p (H/E) = [p (E/H) x p (H)]/ p (E).

38 I realize I am making assumptions here about the relationship between science and moral values which are beyond the scope of this paper. Some philosophers, known as ethical naturalists, hold that there are moral facts which can be reduced to facts about the natural world and that we can obtain knowledge about moral facts in the same way that we acquire knowledge about scientific or natural facts (see, for example, Brink 1989 ; Jackson 1998 ; Foot 2001 ). Other philosophers, known as ethical non-naturalists, hold that moral facts cannot be reduced to scientific facts because there are no moral facts; or, if there are moral facts, they are facts about properties or phenomena that supervene on or transcend the natural world. We cannot, therefore, obtain moral knowledge (if there is such as thing) in the same way that we would obtain scientific knowledge. Non-naturalists hold that morality is based on intuition ( Moore 1903 ; Audi 2005 ), emotion ( Gibbard 1990 ; Greene 2013 ), culture ( Harman 1996 ), religion ( Adams 1987 ), or rational reflection ( Kant 1981 ). I would describe my approach as a limited form of non-naturalism that recognizes that some of our moral values, including human life, freedom from pain, health, have a solid basis in nature but that others, such as justice and human rights, do not. For further discussion of naturalism and non-naturalism, see Lenman (2018) and Ridge (2019 ).

39 Wendler et al. (2005) attempt to quantify the concept of minimal risk for pediatric research in terms of the average daily life risks faced by US children. This attempt to quantify risk, even if successful, would not prove that risk/benefit determinations are quantifiable because these determinations involve judging the risks are reasonable (or morally acceptable) in relation to the benefits, and saying that a risk is reasonable is a value judgment ( Resnik 2017 ).

40 See note 40 .

41 A legal analogy may be useful here: all members of a jury, regardless of their background or education, are obligated to use the same standard of evidence.

42 Human subjects often still fail to understand that they may not benefit from participation, however ( Appelbaum et al. 1987 ; Joffe et al. 2001 .

43 One might also ask whether the IRB should require less evidence for some types of research, such as research that imposes minimal risks on human subjects. While it makes some sense to say that evidence for the reasonableness of risks not need to meet the clear and convincing standard, I would argue that evidence pertaining to other criteria, such as consent or equitable subject selection, would still need to meet the clear and convincing evidence standard, because these criteria involve issues related to human rights.

44 The research may offer these subjects other types of benefits, such as immunity to COVID-19, priority access to COVID-19 therapeutics if they become ill, or the satisfaction that they are contributing to a worthy cause, but these benefits are usually not considered to be direct benefits of the interventions under investigation ( King 2000 ; Friedman et al. 2012 ). Moreover, these other benefits do not outweigh the risks to subjects, so the primary justification for this research is that it is likely to offer significant benefits to society ( Shah et al. 2020 ).

45 I am tempted to suggest that evidence should meet the beyond reasonable doubt standard, but that would probably be too restrictive.

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Office of Research and Sponsored Programs

Institutional review board.

The purpose of the Institutional Review Board (IRB) is to ensure ethical treatment of research participants. IRB review for protection of human participants in research is a matter of institutional policy and federal law. The Belmont Report  outlines the purpose of identifying the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and developing guidelines to assure that such research is conducted in accordance with those principles. All research involving human participants (subjects) must be reviewed and approved by the University's IRB before you begin collecting data. This peer review ensures that adequate measures are being used to protect the individuals who volunteer to participate in your study. All human research must be approved by the IRB. No research is exempt from review. The IRB reviews all proposed human subjects research in which the institution is engaged involving:             1. Intervention or interaction with human subjects           2. Collection of identifiable private data on living individuals           3. Data analysis of identifiable private information on living individuals What is a human subject? A living individual about whom an investigator (professional or student) conducting research obtains data through intervention or interaction with the individual, or identifiable private information ( 45 CFR 46 ). Identifiable information can be linked to a specific individual, either directly or indirectly, through coding systems. 

What is research?  Research is defined by the U.S. Department of Health and Human Services as a "systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. ( 45 CFR 46 ) To be considered a systematic investigation the concept of a research project must:

• Attempt to answer research questions (in some research this would be a hypothesis).
• Be methodically driven, that is, it collects data or information in an organized and consistent manner.
• Analyze data or information in some way- whether quantitative or qualitative data.
• Draw conclusions from the results.

For a project to contribute to generalizable knowledge,  the project results/knowledge gained must: 

• Contribute to a theoretical framework of an established body of knowledge.
• The primary beneficiaries of the research are other researchers, scholars and practitioners in the field of study.
• There will be publication, presentation, or other distribution of the results intended to inform the field of study.
• The results are expected to be generalized to a larger population beyond the site of data collection.
• The results are intended to be replicated in other settings.

When is UW Stevens Point engaged in research?           1. Research conducted by any faculty or staff member, student, or visiting faculty scientist drawing salary for a UWSP sponsored project           2. Research conducted by affiliated faculty under UWSP guidance           3. Non-UWSP personnel using UWSP facilities/equipment not readily available to the public at large

Office of Science Policy

Clinical Research

Of NIH’s more than $17B investment, clinical trials (~$7B ) reflect the point at which the public is most directly engaged in NIH’s clinical research activities, either as dedicated volunteer research participants or users of the resulting data and health interventions. Successful management and oversight of the clinical trial enterprise remains essential to NIH’s mission to translate basic biomedical discoveries into improved health outcomes. OSP works to ensure that NIH’s clinical trial policies enhance the design, conduct and oversight of clinical trials.

Clinical Trials

• Clinical Trials E-Protocol Tool

Informed Consent

Nih single irb (sirb) policy, data and safety monitoring, protections for participants in research (human subjects research protections), privacy and confidentiality in research, return of research results.

• sIRB Policy Implementation

NIH Definition of Clinical Trial

A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.

• Notice of Revised NIH Definition of “Clinical Trial” Revised NIH Clinical Trial Definition
• NIH’s Clinical Trial Definition
• Does Your Human Subjects Research Study Meet the NIH Definition of a Clinical Trial?

Sharing Clinical Trial Information

HHS Final Rule for Clinical Trials Registration and Results Information Submission

• Federal Register Notice of Final Rule for Clinical Trials Registration and Results Submission
• NPRM Clinical Trials Registration and Results Submission (November 2014)
• Summary of the Final Rule and NIH Policy
• Key Elements of Final Rule and NIH Policy
• Summary Table of Changes from Current Practice Described in the Final Rule
• Federal Register Notice for NIH Policy on the Dissemination of NIH-Funded Clinical Trials
• NIH Guide Notice
• Federal Register Notice
• Compendium of Comments

GCP Training for NIH Awardees Involved in NIH-funded Clinical Trials

• Policy on Good Clinical Practice Training for NIH Awardees Involved in NIH-funded Clinical Trials
• FAQs_on_NIH_GCP_Policy

Clinical Trial Enrollment Workshop (July 2015)

NIH Workshop on the Enrollment and Retention of Participants in NIH-funded Clinical Trials July 25, 2014

• Poster Abstracts
• Poster Abstract for Poster Presentation
• Proceedings

Presentations:

• Moon Chen Ph.D.,M.P.H, University of California, Davis
• Jonathan Ellen M.D., John Hopkins University
• Maria Freire Ph.D., FNIH
• Joseph Unger Ph.D., Fred Hucthinson Cancer Research Center
• Jeffrey Vigne, Friends of NIH
• Mary Woolley, Research! America
• ClinicalTrials.gov
• Clinical Trial Requirements for Grants and Contracts
• ICH E6 (R2) Good Clinical Practice (GCP) Integrated Addendum to ICH E6 (R1)
• New Review Criteria for Research Project Applications Involving Clinical Trials
• NIH ClinRegs
• NIH Clinical Trials and You
• NIH Stem Cell Clinical Trials & Other Information
• Regulations: Good Clinical Practice and Clinical Trials 
• Research Methods Resources
• OSP-OER Blog “Improving Visibility of NIH-Supported Clinical Trial Activities and Results Information”
• OSP-OER Blog “Building Better Clinical Trials through Enhanced Stewardship and Transparency”
• JAMA Article “Toward a New ERA of Trust and Transparency in Clinical Trials”
• NEJM Article “The Final Rule of U.S Clinical Trials Registration and Results Information Submission”

Clinical Trial E-Protocol Tool

Clinical trial e-protocol tool and template documents.

The  electronic protocol writing tool  aims to facilitate the development of two types of clinical trials involving human participants.  The first type of trials are Phase 2 and 3 clinical trial protocols that require a Food and Drug Administration (FDA) Investigational New Drug (IND) or Investigational Device Exemption (IDE) application.

NIH developed a second protocol template to help behavioral and social science researchers prepare research protocols for human studies measuring a social or behavioral outcome or testing a behavioral or social science-based intervention.

Both templates found in the electronic protocol tool meet the standards outlined in the  International Council on Harmonisation (ICH) Guidance for Industry, E6 Good Clinical Practice: Consolidated Guidance (ICH-E6) . These are international standards of good clinical practice that apply to all clinical trials, and their goals are to ensure research integrity and protect human subjects. In addition, use of the electronic protocol tool allows researchers to interface directly with clincialtrials.gov.

Take me to the Web-based e-Protocol Writing Tool

• Word Version of Final Template
• NIH Director’s Statement
• Under the Poliscope  blog
• Under the Poliscope  Blog

As a steward of the nation’s biomedical research enterprise, NIH is dedicated to ensuring that data and biospecimens are shared for research ethically, securely, and with respect for the privacy, autonomy, and well-being of research participants and the communities to which they belong. Responsible sharing of data and biospecimens derived from human participants relies on robust informed consent practices that uphold the principles of autonomy and trust in biomedical research. Fundamental to these practices are clear, efficient, and transparent communication strategies for conveying potential risks and benefits of sharing, enabling individuals to make informed decisions to participate in research, retain autonomy in decision making, and understand potential uses and contributions of their data and specimens.

OSP works to ensure robust informed consent practices are understood and in place across NIH, with the goal of protecting research participants altruistically donating data and specimens to advance the scientific enterprise.

Relevant Documents and Resources

• Informed Consent for Secondary Research with Data and Biospecimens: Points to Consider and Sample Language for Future Use and/or Sharing
• Request for Information: Developing Consent Language for Future Use of Data and Biospecimens
• Public Comments

The NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research establishes the expectation that all sites participating in multi-site studies involving non-exempt human subjects research funded by the National Institutes of Health (NIH) will use a single Institutional Review Board (sIRB) for all U.S. sites to conduct the ethical review required by the Department of Health and Human Services regulations for the Protection of Human Subjects. If you have any questions about this policy, please contact us  here .

• NIH Single IRB Policy
• Final NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research
• Federal Register Notice on the Final NIH sIRB policy
• Federal Register Notice on sIRB Effective Date Extension
• NIH Guide Notice on the Final sIRB policy
• NIH Guide Notice on sIRB Effective Date Extension
• NIH Director’s Statement on the NIH sIRB policy
• OSP-OER Blog on the sIRB policy
• NCATS SMART IRB Reliance Platform
• Frequently Asked Questions about the Implementation of the sIRB policy
• NIH Guide Notice on Scenarios Illustrating the Use of Direct and Indirect Costs for Single IRB Review Under the sIRB Policy
• NIH Policy on the Use of a Single IRB for Multi-Site Research FAQs on Costs
• Request for Comments on the Draft NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research
• Public Comments on the Draft Policy
• New Federal Register Notice regarding the extension of the effective date for the Single IRB policy

Single IRB Review for Multi-Site Research Resource and Infrastructure Development Workshop (September 2018)

On September 12, 2018, NIH held a Workshop on Single IRB Resource and Infrastructure Development.  The workshop focused on successful strategies and lessons learned for modifying and enhancing institutional IRB infrastructure for single IRB review of multi-site studies.

Agenda Biographies Relevant Information and Resources

Presentations: SESSION I – Customizing eIRB Systems to Review Multisite Studies Using a Single IRB Model, Medical University of South Carolina SESSION I –  Models for Institutions Serving as sIRB of Record, Washington University SESSION I –  Single IRB Standard Best Practices, New York University SESSION II –  Models for Assisting Institution Relying on sIRB – Partnership and Innovation Exploring Single IRB Models to Support Clinical and Translational Research, Yale University SESSION II –  Models for Assisting Institutions Relying on sIRB – Incorporating sIRB Procedures into an Existing Research Network, University of Rochester SESSION III –  Facilitating Single IRB Review for Multi-site Research:The OneIRB IT Platform, University of Penslyvania SESSION III –  Administrative Supplements for CTSA Awardees: Development of Resources to Facilitate Single IRB Review for Multi-Site Research, University of Cincinnati Webcast

Clinical trials must be conducted with a high standard of quality that assures the research question is answered in a reliable, valid, and unbiased manner, and that the rights and welfare of human subjects are protected.

In 1998, NIH issued a  policy  and further  guidance  was published in 2000. The NIH Data and Safety Monitoring policy states that each NIH Institute and Center (IC) should have a system for appropriate oversight and monitoring of clinical trials in order to ensure the safety of participants and the validity and integrity of the data. The 1998 and 2000 policies provide guidance on when monitoring should be conducted by a Data and Safety Monitoring Board (DSMB). The NIH requirement for data and safety monitoring –at a level commensurate with the risks, size and complexity of the trial–is separate and distinct from the requirement for protocol review and approval by an Institutional Review Board (IRB).

• Healthcare Research and Quality (AHRQ) Data and Safety Monitoring Policy
• Office for Human Research Protections (OHRP): Guidance on IRB Continuing Review of Research
• FDA Guidance for Clinical Trial Sponsors: Establishment and Operation of Clinical Trial Data Monitoring Committees
• NIH Policy for Data and Safety Monitoring, June 10, 1998
• Further Guidance on a Data and Safety Monitoring for Phase I and Phase II Trials, June 5, 2000
• Guideline on Data Monitoring Committees (European Medicines Agency, July 27, 2005)
• Operational Guidelines for the Establishment and Functioning of Data and Safety Monitoring Boards (World Health Organization)

Participants in NIH-funded clinical research studies receive a robust set of protections in accordance with standards established by the U.S. Department of Health and Human Services (HHS) in 45 Code of Federal Regulations (CFR) part 46 (“the Common Rule”), and, when applicable, Food and Drug Administration (FDA) Regulations for 21 CFR Part 50 and 56. Additional protections for research participants are also established under Section 2012 and 2013 of the 21st Century Cures Act, the NIH Certificates of Confidentiality policy, the Privacy Act, and the HIPAA Privacy Rule. Protections provided by the Common Rule ensure the safety, rights, and welfare of participants in research (what the Common Rule calls “human subjects”) under a framework that prioritizes the ethical principles enshrined in the Belmont Report (i.e., respect for persons, beneficence, and justice). These protections include oversight of research by Institutional Review Boards (IRBs), as well as requirements for informed consent, confidentiality, and privacy.

OSP serves as a resource for and advisor to the NIH research community with respect to the implementation of regulations, laws, and policies impacting the protection of participants in NIH research. OSP advises on harmonization and optimization, works with NIH Institute, Center, and Office (ICO) partners to identify and resolve policy issues, and recommends and develops new policies as needed. OSP works closely with colleagues across NIH and HHS, including NIH ICOs as well as FDA, the Department of Defense (DOD), the Department of Veteran’s Affairs (VA), the HHS Office for Human Research Protections (OHRP), and the HHS Secretary’s Advisory Committee on Human Research Protections (SACHRP).

• Common Rule: 45 CFR Part 46
• FDA Regulations for 21 CFR Parts 50 and 56
• NIH Human Subjects Research Policies and Policy Notices
• Office for Human Research Protections
• Secretary’s Advisory Committee on Human Research Protections (SACHRP)

Privacy and confidentiality are essential components of a robust research enterprise. NIH takes seriously the obligation to ensure privacy and confidentiality for individuals who have altruistically provided data and samples for research. Some of the obligations for these protections are outlined in the Common Rule, which describes a framework for protecting the privacy and confidentiality of sensitive, private information. Additional protections are provided by Section 2012 and 2013 of the 21st Century Cures Act and the NIH Certificates of Confidentiality Policy, which ensure appropriate protections for research when identifiable, sensitive information is collected or used. The Privacy Act and HIPAA Privacy Rule outline further protections for when individual data subject to these laws can be released.

OSP serves as a resource and advisor to the NIH research community on privacy and confidentiality regulations, laws, and policies. OSP advises NIH ICOs on these protections and works with ICOs to identify and resolve any policy issues.

• Common Rule: 45 CFR Part 46
• 21 CFR part 50 and 56 FDA Regulations for the Protection of Human Subjects
• Section 2012 and 2013 of the 21st Century Cures Act Provision on Certificates of Confidentiality
• NIH Certificates of Confidentiality policy
• NIH Certificates of Confidentiality website
• Privacy Act
• HIPAA Privacy Rule
• 2013 Privacy Rule Amendments
• HIPAA Privacy Rule and Its Impacts on Research (nih.gov)

NIH has long supported a movement in the research enterprise to engage participants as partners in research by informing research priorities and advising on clinical study designs to ensure that outcomes are meaningful to them. Research participants, for their part, have indicated the desire to have information returned to them about the studies in which they participate, including individual-level research results. In 2018, NIH co-sponsored a study by the National Academies of Sciences, Engineering, and Medicine (NASEM) to examine Returning Individual Research Results to Participants , specifically reviewing the current evidence on the benefits, harms, and costs of returning individual research results while considering the ethical, societal, regulatory, and operational issues related to the return of individual-specific research results generated from research on human biospecimens. In recognition of the evolving nature of research and the relationship between research participants and investigators, as well as the responsibility to uphold participant preferences, various programs and initiatives across NIH are moving towards creating a more participatory model of enabling greater return of individual-level research results.

OSP serves as a resource for and advisor to the NIH research community with regard to identifying and resolving policy issues and promoting best practices for the appropriate return of individual research results to participants.

Funding Opportunities Across NIH (updated 4/3/23)

• Strategies for Responsibly Reporting Back Environmental Health and Non-Genomic Research Results (R01 Clinical Trial Optional)

Select Return of Research Results Efforts at NIH

The below list of programs and initiatives is non-exhaustive and highlights select examples that include either a focus on returning research results from particular studies or promoting the development of tools and best practices to enable return of results.

• All of Us Research Program
• Return of Research Results webpage
• CLINSEQ®: A Large-Scale Medical Sequencing Clinical Research Pilot Study
• Clinical Sequencing Evidence-Generating Research (CSER) Consortium
• Electronic Medical Records and Genomics (eMERGE) Network

Select Resources

• Clinical Laboratory Improvement Amendments of 1988 (CLIA)
• The Secretary’s Advisory Committee on Human Research Protections (SACHRP) Recommendation for Return of Individual Research Results—Sharing Study Data and Results: Return of Individual Results
• OSP Blog: Recommendations for Moving to a Process for Returning Research Results
• OSP Blog: A Fresh Look at the Rules for Returning Research Results

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Office of the Vice President for Research

Irb virtual office hours 4/22 & 4/23.

Research Integrity & Compliance (RIC) will hold office hours via Webex extending support to both students and faculty regarding IRB submissions and regulations pertaining to human subjects research. Late afternoon appointments are made available to accommodate the schedules of students and faculty researchers. Evening appointments are available upon request.

Research Integrity & Compliance (RIC) staff are available to answer questions for research teams and faculty and student investigators who have questions about submitting to the IRB, human subjects regulations, post-approval support, or general queries related to IRB procedures.

Virtual office hours will be held on the following dates and times:

Monday April 22, 2024, from 2:00pm-5:00pm

Tuesday April 23, 2024, from 10:00am-1:00pm

When reserving a slot, it is helpful to add information under “reason” why you would like to meet with RIC staff. You will receive a confirmation email from Nexus that includes the Webex link. Please use the following Nexus link to sign up for an open meeting slot to schedule an appointment:

https://nexus.uconn.edu/secure_per/schedule1.php?stser=4475

For questions related to the sessions, please contact Joan Levine at [email protected]

COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK

IRB Specialist

• Columbia University Medical Center
• Opening on: Apr 20 2024
• Job Type: Officer of Administration
• Bargaining Unit:
• Regular/Temporary: Regular
• End Date if Temporary:
• Hours Per Week: 35
• Standard Work Schedule:
• Salary Range: $65,000 - $75,000

Position Summary

The IRB Specialist will join a team of other professionals who are responsible for conducting pre-reviews of submissions to CUMC IRBs, including new protocols, continuing reviews, modifications, and unanticipated problems. This staff member may regularly or on a periodic basis attend IRB meetings and also provide support to the incumbent's Manager, IRB Chair, and IRB Members, including writing and editing minutes of meetings. Additionally, the IRB Specialist will have responsibilities related to the generation, review, and release of IRB correspondence.

Responsibilities

The IRB Specialist will conduct quality control functions for the IRB office that may extend to all areas of the operation including review of files and meeting minutes for completeness, accuracy and consistency. Further, this staff member will work with other IRB officers of administration and staff to ensure uniformity of review and compliance with IRB standard operating procedures and applicable federal and state regulations. The IRB Specialist will also serve on relevant IRB administrative committees, such as the Policy Committee and the Education and Training Committee. In addition, this candidate will maintain up to date knowledge of state and federal regulations as well as policies, guidelines and ethical codes related to the protection of human subjects in research. Other work as assigned, which may include but is not limited to special projects or assisting a team other than the one to which the individual is assigned.

Minimum Qualifications

• Requires a bachelor's degree or equivalent in education and experience, plus three years of related experience of which two years should be of prior IRB and/or research experience.

Preferred Qualifications

• Experience with biomedical or behavioral and social sciences human research is preferred. Knowledge of international ethical codes and regulations governing human subjects is preferred. Certification as an IRB professional is also preferred.

Other Requirements

• Familiarity with state and federal regulations related to human subjects protection required. Strong interpersonal and writing skills and experience with computerized databases and word processing is essential.

Equal Opportunity Employer / Disability / Veteran

Columbia University is committed to the hiring of qualified local residents.

Commitment to Diversity 

Columbia university is dedicated to increasing diversity in its workforce, its student body, and its educational programs. achieving continued academic excellence and creating a vibrant university community require nothing less. in fulfilling its mission to advance diversity at the university, columbia seeks to hire, retain, and promote exceptionally talented individuals from diverse backgrounds.  , share this job.

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