Human Research Protection Program: Policy

IRB Analysis of Risks and Benefits of Research

 

Adopted by: All Campus IRB

Adoption Date: November 10, 2005

Purpose:  This document describes how UW-Madison IRBs analyze the risks and benefits of proposed research when reviewing protocols.

Definitions

I.      Risk: The probability of harm or injury (physical, psychological, social, or economic) occurring as a result of participation in a research study. Both the probability and magnitude of possible harm may vary from minimal to significant.  “Minimal” risk is defined by federal regulations. [45 CFR 46.102(i) and 46.303(d); 21 CFR 50.3(k) and 56.102(i)]

II.     Benefit: A valued or desired outcome; an advantage. The benefits of research fall into two major categories: benefits to participants and benefits to society.  Some research has therapeutic intent, e.g., research that evaluates a procedure that may ameliorate participants’ medical conditions or provide a better understanding of their disorders.  Some research has no immediate therapeutic intent but is designed principally to increase our understanding and store of knowledge about human physiology and behavior.  Non-therapeutic research may benefit society as a whole by increasing knowledge and improving safety, technological advances, and health.

Policy

I.      At UW-Madison, IRB review of research involving human participants is not primarily a review of the science of a research protocol.  Rather, UW-Madison IRBs’ main concern is how the science affects those people who will participate in the research. 

II.     An IRB must judge whether the anticipated benefit, either of new knowledge or of improved health for the research participants, justifies inviting any person to undertake the risks. The IRB should disapprove research in which the risks are judged unreasonable in relation to the anticipated benefits.

III.    Evaluation of the risk/benefit ratio is the major ethical judgment that IRBs must make in reviewing research proposals. The risk/benefit assessment is not a technical one valid under all circumstances; rather, it is a judgment that often depends upon prevailing community standards and subjective determinations of risk and benefit.

Procedure

I.      In analyzing the risks and benefits of proposed research, the IRBs consider the following questions:

 

1. What risks will participants be exposed to that are different from the risks of standard therapy (or everyday life, if participants are not currently suffering from or being treated for any condition).

 

1.       Risks can be:

 

a.    Physical (pain, discomfort, risks to health)

b.    Social, Psychological, Emotional (invasion of privacy, loss of confidentiality,

harassment)

c.   Economic (damage to reputation, loss of insurance, impact on employability)

d.    Legal

 

2.       Risks should be evaluated for frequency, severity, and reversibility and possible late effects of participation.

 

3.       The IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies participants would receive even if not participating in the research).

 

4.       The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.

 

2. Are risks identified clearly and accurately in the protocol and/or application.

 

3. Whether participants will include children or any other vulnerable population and whether there are special risks for these vulnerable groups and how are these risks addressed.

 

4. If deception will be used, is it necessary and justified and will debriefing be adequate.

 

5. Are risks kept to a minimum with measures such as:

 

1.       Appropriate eligibility criteria (screen out the especially vulnerable) [See, Participant Recruitment Policy]:

 

a.   Assure that proposed participant population is appropriate to the research.

b.   Whether recruitment excludes those participants for which the risks are more likely to occur or are unacceptable.

c.    Assure that recruitment is free of coercion and undue influence.

d.   Assure that there is no status relationship between research team and participants.

 

2.       Measures to make study procedures as comfortable as possible for participants.

 

3.       No unnecessary or excessive testing.

 

4.       Study-wide monitoring of safety and data integrity.

 

a.    Appropriate lab tests and other individualized monitoring.

 

5.       Good study design, so that the risks participants take result in usable information (the riskier the research, the better the study design must be).

 

6.       Whether there are provisions for ensuring necessary medical or professional intervention in the event of adverse effects to the subjects or additional resources for participants.

 

7.       Whether the research personnel are qualified to perform the research or, in the case of student research, is the level of supervision adequate.

 

6. What will study participation feel like to the participant:

 

1.       How many visits and how long will they take.

 

2.       What kinds of procedures are involved.

 

3.       How do the study procedures differ from standard care.

 

4.       Will subjects be compensated for participating in the study, and if so, how.

 

5.       Any unusual, invasive, or sensitive procedures (e.g. excessively long or frequent visits, many needle sticks, genetic testing).

 

7. Will the participant be told about the study in a way he/she can understand, so the participant can make an informed choice about taking part:

 

1.       Consent form content and readability are key.

 

2.       Also important are procedures for obtaining consent and ongoing dialogue with participants about their study involvement.

 

3.       Are risks identified clearly and accurately for participants.

 

8. Are there provisions to maintain the privacy of the subjects and confidentiality of the data and research records:

 

1.       Recording and coding of data.

 

2.       Identifiability of data.

 

3.       Is the research data kept in a secure location:

 

a.   Storage of data.

b.   Storage of subject samples such as saliva, blood, and tissue (see UW HSC Guidelines for Genetics & Storable Tissue).

c.   If electronic data storage, is there adequate firewall and other electronic protection.

 

4.       Sharing of data:

 

a.    Are formal confidentiality agreements used.

b.    Is a Certificate of Confidentiality needed.

 

5.       Are the research procedures being performed in a location that protects the privacy of participants.

 

6.       Participants’ dignity should be preserved.

 

9. What are the expected benefits:

 

1.       Benefits can take the form of therapy, education, information, resources or empowerment.

 

2.       Benefits can be directed at participants or their community or society.

 

3.       If no benefit to participants, is the issue being researched important to society.

 

4.       If the stated intent is to benefit participants, is it true benefit.

 

5.       Benefit may exist from participation in study even if the actual research does not provide participant benefit: e.g., participants’ conditions more closely monitored, free medical treatment provided to participants than they otherwise would get.

 

6.       If protocol will provide no benefit to participants, protocol must say so.

 

10. Are the risks of the research reasonable in relation to the benefits:

 

1.       Requires balancing of potential risks to participant or to others (e.g., disclosure of genetic information) with potential benefits to participant and to society.

 

2.       Sliding scale used ranging from

 

a.    little or no benefit to participants requires little or no risk.

b.    high risk studies require showing of significant benefit to participant.

 

3.       Whether balance is reasonable may require consideration of type of risks: physical, psychological, sociological, economic, or legal.

 

4.       Long-term effects considered.

 

5.       Reviewers document risks presented by research, steps to minimize risks, and benefits, if any, to participants, importance of issue being researched, and alternative treatments available to participants.

 

6.       If more than minimal risk or vulnerable population, analysis of balance becomes more important.

 

K.      Additional considerations for clinical research:

 

1.       Risks often involve physical risks and may include the possibility of death.

 

2.       If the participant is currently being treated for a medical condition, the IRB will expect that research procedures be piggybacked on procedures currently being used to diagnose or treat participant’s condition, if possible; if not, justification will be required.

 

3.       The phase of the research with respect to a particular drug, device or procedure.

 

4.       The medical condition of the participant (how ill is the participant).

 

5.       Are there other appropriate medical treatments for the condition and the effectiveness and availability of the alternative treatments and the comparative risks they present.

 

6.       Possible late effects of participation (e.g., secondary cancers).

 

7.       What drugs or therapies are used, and what dose levels.

 

8.       Are samples of blood, tissue, etc. collected.  Are they banked.

 

9.       If a more than minimal risk study, is an adequate data and safety monitoring plan in place.

 

L.       Additional considerations for social and behavioral science and education research:

 

1.       Risks are primarily social, psychological, economic and legal and only rarely physical.

 

2.       Some research presents little or no benefit to the individual participant and will not be approved unless the protocol presents very low risk to participants. 

 

3.       If protocol is risky (e.g., involves sensitive information), the investigator is required to show how he/she will mitigate the potential risks through confidentiality measures or assurances of anonymity.

 

4.       In international research, investigator must address potential cultural, political and economic risks peculiar to the country in which the research is being conducted.

 

5.       If a research instrument (e.g., questionnaire) is likely to reveal sensitive information about a participant that is unnecessary to the research being conducted, a different instrument should be used.

IV.   In each case, the risk/benefit analysis is based on the information included in the Application for Initial Review, Continuing Review or Change of Protocol/Progress Report and the investigator’s statements about the risks and benefits and any mitigating factors as well as the reviewer’s subject matter expertise.  In the case of protocols involving investigational drugs, the analysis also includes an evaluation of the information in the Investigator’s Drug Brochure, if applicable. 

V.    The analysis of risks in relation to benefits of proposed research is conducted by the full IRB, by primary reviewers and, in the case of health sciences protocols, by staff reviewers. 

A.  When staff reviewers are used, the staff reviewer prepares a risk/benefit analysis that considers the information submitted by the investigator relating to (1) what is known about the study drug, device and intervention in terms of risks and efficacy, (2) whether the appropriate subject population is targeted by the research, including a consideration of eligibility criteria, (3) what specific measures are in place to minimize the risks (such as a safety and data monitoring plans and procedures); and (4) whether an appropriate justification for the study design has been provided.  Staff reviewers comment on potential concerns raised by the study design in terms of risk/benefit ratio and make recommendations for modifications, clarifications, or additional expert review if the reviewer notes concerns.  These written analyses are provided to primary reviewers and IRB members for consideration in their review and discussion of a protocol.

B.  When primary reviewers are used, the primary reviewers lead the discussion of the risk/benefit analysis with the full IRB and make the case either that the risks versus benefits ratio is acceptable or that changes need to be made.  The full IRB ask questions to ensure their understanding and make suggestions for changes/clarifications.  The riskier the protocol, the more lengthy and detailed the discussion by the full IRB. 

C.  Some IRB members (e.g., biostatistician, Pharmacy Research Center representative) review the protocols in detail to ensure their areas of concern (the statistical design, the handling of the experimental drug) are addressed. 

D.  The IRB Chair clearly summarizes the concerns discussed and required changes before the full IRB votes on the protocol.