Ethical Review Process

by the IRB_________________________________

Presented By-MANISH KUMAR SHARMA D.PHARMA,B.PHARMA, PGDCR DEPARTMENT OF CLINICAL RESEARCH SHARDA UNIVERSITY, GREATER NOIDA,UP

The purpose of an IRB is to Review research and to Ensure the rights and welfare of human subjects involved in research are adequately protected.

IRB Function

Why Do Human Research Subjects Need Protection?

Trigger Events Ethical Milestones

The Nazi Experiments Nuremberg Code 1947

Tuskegee Syphilis Study National Commission for the Protection of Human Subjects of Biomedical &

Behavioral Research 1974

* Belmont Report 1978* Common Rule 1991

1. Respect for Persons

2. Beneficence

3. Justice

The Basic Principles of the Belmont Report

Regulatory Requirements for IRB Approval

Risks to subjects are minimized

Risks are reasonable in relation to anticipated benefits – if any

Selection of subjects is equitable

Informed consent will be sought and appropriately documented

When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects

Regulatory Requirements for IRB ApprovalWhen appropriate, there are adequate provisions to protect

the privacy of subjects and to maintain the confidentiality of data

When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included to protect the rights and welfare of these subjects.

IRB Review of Research All research projects are categorized into one of three

categories for the IRB review process. Each category is different in the level of scrutiny and submission procedures. The IRB is responsible for making the final decision of which category a research project falls under.

Full Expedited Exempt Research Not Involving Human Subjects

Full ReviewOne or more Committee member(s) are assigned to

review the complete protocol or amendment, consent form, Investigational Drug/Device Brochure and any other protocol materials. 

These Primary & Secondary Reviewers summarize the protocol or amendment to the Full Committee at a convened meeting and answer questions during the discussion.

All other committee members are provided with summary information, for example the Protocol Cover Form and informed consent document.  This stresses the importance of the accuracy and details provided in these documents, since the majority of voting members only see these 2 documents!

Expedited ReviewProtocols, amendments, or continuing reviews

that meet specific federal criteria qualify for an expedited review. 

The complete protocol, consent form, and any other protocol materials receive review and approval by a Committee Chair.

Expedited does not mean “fast” it is a regulatory term used for research that must meet specific criteria

Some CommonExpedited Review CategoriesContinuing Review when: the research is

permanently closed to the enrollment of new subjects; (ii) all subjects have completed all research-related interventions; and (iii) the research remains active only for long-term follow-up of subjects; or

(b) where no subjects have been enrolled and no additional risks have been identified; where the remaining research activities are limited to data analysis.

Some CommonExpedited Review CategoriesAnd when the IRB has determined and documented at a

convened meeting that the research involves no greater than minimal risk and no additional risks have been identified.

Exempt from IRB ReviewCommittee review is not required for certain

categories of research activities that involve little or no risk to human subjects. 

 To determine if your research qualifies for

exemption from formal committee review, complete the “Protocol Exemption Review and Determination Checklist.” 

Only the IRB can make the determination of Exempt, this cannot be determined by researchers!

What about pilot studies?Whether or not a pilot study requires IRB approval

depends on the nature of the data collected in the pilot

For example, we have a study of drug use among high school students in Kenya

If the pilot study involves testing the research instruments on high school students, asking them questions about drug use – then this DOES require IRB approval

If the pilot involves asking students to give views on the the questionnaire design/ content then this DOES NOT require IRB approval

IRB Review and Determination of “Research Not Involving Human Subjects”

There is some research that involves coded private information or specimens that do not involve human subjects.

When conducting research using data or specimens, the level of review by the IRB depends primarily on one factor: whether the data or specimens are identifiable to the principal investigator or key personnel.

Determinations of whether research involving coded private information or biological specimens is considered to be “human subjects research” must be made by the IRB, not the investigator. 

The IRB submission packet must include The protocol and any amendments, informed consent, and the investigator brochure. The Investigator’s Undertaking; CVs (curriculum vitae) can verify the investigators' qualifications. All advertising materials also require approval. Payments to subjects require approval and may be a source of contention between the investigator and IRB.

Types of ReviewInitialContinuing ReviewAmendmentsSafety Information or Unanticipated

Problems to Subjects or OthersNoncompliance

While Review the IRB checks…

• Risks are Minimized (Consistent with a sound research design and does not unnecessarily expose subjects to risk)

• Risks are Reasonable in Relation to Benefits• Selection of Subjects is Equitable• Informed Consent will be Sought for Each Prospective

Subject• Informed Consent will Be Documented• Research Plan Adequately Provides for Monitoring the Data

Collected to Ensure Safety of the Subjects• Research Plan Adequately Protects the Privacy of Subjects

and Maintains Confidentiality• When some or all of the subjects are likely to be vulnerable to

coercion or undue influence, additional safeguards need to be included in the protocol to protect the rights and welfare of these subjects.

The IRB has the authority to:

oApprove

oRequire modifications prior to approval

oTableoDisapprove all research activities including proposed changes in previously approved human subject research.

How the IRB System Works

Primary and Secondary ReviewersAssignments made 1 week ahead of meeting

Discussion by Full CommitteeReviewers lead discussion Everyone contributes

Committee VoteApproveConditional ApprovalDeferralDisapprove

Determining an ActionApproval – the criteria for approval are met.Conditional approval – IRB stipulates specific revisions

requiring simple concurrence by the investigator, then the IRB Chair or another IRB member designated by the Chair subsequently approve the revised research protocol on behalf of the IRB.

Deferral - substantive clarifications or modifications required that are directly relevant to the criteria for approval.

Disapproval – major ethical or scientific issues – PI can respond to the IRB or start over.

Review Strategy

Review application Look for special issues such as kids, radiation, emergency use

issues, new drugs/devices, genetics, storing samples for future use

Read protocol summary Look for site specific issues; can we logistically perform the

study here?

Read detailed protocol Look also at any study specific tools, letters, ads, extras

Review Strategy

Prepare your comments Written and submitted are wonderful Emailed is even better

Editing the consent form Edit right on the document Use legible handwriting Submit marked up document

Background and Specific AimsShould contain a convincing summary of

previous work and rationale for the study

References should be included

There should be clear aims and endpoints

Subject Selection and Enrollment

How are subjects identified? Ads, charts, RPDR, referrals, PI’s own clinic, support groups,

public records.

How, when and by whom are subjects for contacted about study? In person? Should be by someone who has reason to know

confidential medical information. Letters? Letters should be co-signed by the MD know to the

patient-subject. No cold calls

Subject Selection and EnrollmentInclusion/Exclusion Criteria

Should be a concisive list Should include appropriate laboratory parameters Should include appropriate medical exclusions Should not/rarely exclude non English speakers

Who obtains consent? Who gives consent?

Study ProceduresShould include sufficient detail to ascertain

what subjects will actually experience while in study

Time commitment. Setting or site where study procedures occur. Any “routine” agents to be used – such as sedation. Consent form with detail in lay terms.

BiostatisticsA formal sample size is generally necessary.Why does the PI need this many subjects?Are there enough subjects to answer the

study question?How are the data to be analyzed?Just because the PI says it is a pilot study

doesn’t mean they don’t need statistics.

Risks and DiscomfortsShould be listed clearly, quantitatively and in

order of seriousness.Should include risks of withdrawal from current

medications.Non medical risks? Social, legal, financial or

psychological risks? Is loss of confidentiality a legitimate risk or concern?What about loss of privacy?Is there a complete list of adverse events in the drug or

device brochure?Any foreseeable but maybe still theoretical risks – for

example tumorigenesis?

BenefitsCompensation is not a benefit

If there are benefits to the individual subjects these should be discussed first, then any potential benefits to future society

A common error we see is the “overstatement” of benefits.

Example of good benefit statement: There will be no direct health benefits to you as a result of your participation in this study.

Safety MonitoringHow are the data to be monitored and by whom?

All studies involving more than minimal risk require a data and safety monitoring plan.

Not all studies require a DSMB but if one is necessary who does it involve? Is it independent? Should it be?

Are there objective criteria for withdrawal of subjects when safety is in question?

Are there stopping rules?Is there a plan for reporting to the IRB?

Common Review IssuesPI has failed to provide information about

reasonable clinical context or apparent withholding of standard of care.

Failure to minimize risk.Inadequate information about collaborating

sites, especially when international sites are involved.

Poor preparation of materials – cutting and pasting errors.

Poor writing skills, no proof reading.

Lets do it together

CASE STUDIES

Scenario 1

Karen goes to work for the Population Council in Nairobi, Kenya on a research project.

The project was conceived and designed by the PC, the PI is a member of the PC staff, who is not IRB Staff.

Karen will be designing research instruments, implementing the survey and managing the project. While in the field, Karen decides she wants to bring the data back to the US to use for her thesis.

.

AnalysisKaren does NOT need IRB approval for her survey.

Responsibility for IRB approval lies with the PI, so the PC should be seeking it’s own IRB approval. Karen will need to be added to their existing IRB approval as study staff

To use the data for her thesis, Karen needs to apply for IRB approval for secondary data analysis & DE identify the data before bringing it back to the US. She can only apply for approval for secondary data analysis once the data collection is complete, and cannot bring the data to the US until she has IRB approval

Scenario 2

Jack goes to Vietnam to work for WHO. They want him to conduct an evaluation of

their immunization program, to identify effective delivery strategies. The results of his work will be used to improve WHO programs in Vietnam.

He does not intends to use the data he collects for his thesis or any other publication

AnalysisJack does NOT need IRB approval.

An internal evaluation, in which the data/ results are not intended to be published or generalized is not considered research, and is thus exempt from IRB review

Scenario 3

Jasmine travels to West Bengal to study infant feeding practices among refugees. Although she submits all her IRB documents in advance, she does not hear from the IRB before her project is due to start. Frustrated, Jasmine decides to go ahead and collect the data, and to apply for retrospective approval once she returns

AnalysisData collection cannot begin without IRB

approval. The instruments can be designed & sampling can begin – but you cannot start collecting data from human subjects without IRB approval. Jasmine cannot apply for retrospective approval or for permission for secondary data analysis. The data cannot be used for any research purposes.