January 29, 2013 | Volume 3, Issue 1

Institution Bulletin Letter from the CEO

Did you have an opportunity to attend the December PRIM&R meeting in San Diego? If so, I hope you saw the exhibit on the Tuskegee Syphilis Experiment by photographer Tony Hooker. The exhibit featured historic photographic images superimposed on contemporary images, as well as personal quotes from individuals involved in the study.

The haunting images of the exhibit made me think of ghosts – the ghosts of the individuals who died and suffered during the trial before it was exposed by a whistleblower. It is believed that of the 400 African-American men who started the study, 28 died directly of syphilis, 100 died of related complications, 40 wives were infected and 19 children were born with congenital syphilis.

The abuses of that trial prompted regulatory action and led to the key components of today’s subject protection requirements, including review by an independent committee, informed consent, and regular continuing review of the merit of the study. It’s vital that those of us involved in the research enterprise revisit Tuskegee regularly to remember the importance of the protections of ethics review.

As the research enterprise has grown and become more complex, so have the requirements and obligations for a human research protection program. Enclosed are two articles to assist your institution in its mission to protect research participants. One article describes the use of screening consent and the other summarizes recent FDA draft guidance on IRB review responsibilities.

Quorum Review is honored to have the privilege to work with you and your institution research teams. Please let us know if we can be of further assistance.

Sincerely,

Cami Gearhart, CEO Quorum Review IRB

CEO Cami Gearhart , JD

January 29, 2013 | Volume 3, Issue 1

FDA’s Draft Guidance for IRBs, Clinical Investigators, and Sponsors

The FDA announced the availability of a new draft guidance entitled Guidance for IRBs, Clinical Investigators, and Sponsors: IRB Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research Sites, and the Determination of Whether an IND/IDE is Needed.i The draft guidance addresses specific IRB responsibilities and explains how an IRB may efficiently fulfill them.

IRB Review of Qualifications of Clinical Investigators and Adequacy of Site

The draft guidance discusses review of an investigator’s qualifications and the research site under two complementary regulatory provisions.

• First, the IRB is obligated to “ascertain the acceptability of the proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice.”1

• Second, the IRB is required to find that risks to subjects are minimized and reasonable in relation to anticipated benefits, if any, to subjects.2

The FDA indicates that the IRB should consider the nature and risks of the proposed research as well as the relationship with the investigator or institution where the research will be conducted when evaluating investigator qualifications and the adequacy of a proposed research site. The draft

i Available at: www.regulations.gov/#!documentDetail;D=FDA-2012-D-0847-0001.

1 21 CFR 56.107(a).

2 21 CFR 56.111.

guidance explains that when an IRB has previous experience with an investigator or institution, it may easily determine the investigator is appropriately qualified and the site is suitable for the research.

With respect to investigators, the draft guidance suggests that the IRB could rely on documentation or a statement from an office at an institution regarding the qualifications of a particular investigator. It is suggested that review of information such as the curriculum vitae of the

investigator and research staff and verification of professional association and medical licensure may only be necessary when the IRB has no knowledge of the investigator or the institution.

The FDA did identify three possible scenarios

that warrant additional attention from the IRB when determining whether an investigator is appropriately qualified:

1. Sponsor-investigator studies

2. A study outside the investigator’s area of expertise

3. Any study design features or other characteristic(s) that may significantly increase potential risk to subjects

January 29, 2013 | Volume 3, Issue 1

Finally, FDA recommends that IRBs routinely review lists on FDA-hosted websites for investigators that have been the subject of investigations and warning letters, investigators that have been notified of initiation of a disqualification proceeding, and also disqualified investigators.

With respect to evaluation of the site, FDA suggests that the IRB could simply note that a particular institution has adequate resources such as emergency or specialized care, rather than requiring the investigator to provide an explanation of such resources if the facility were part of a major medical institution. The draft guidance indicates that a statement from an appropriate person at a research site stating the facilities are adequate could be used in lieu of a statement from an investigator describing the facility, staffing and resources where the research will take place.

IRB Determination of Necessity of an IND or IDE

The draft guidance indicates that IRBs should evaluate the sponsor’s explanation if they have determined that an IND or IDE is not necessary for a particular study. If the IRB questions whether an IND is necessary and the explanation is not

satisfactory, the IRB should delay approval of the study until the matter is resolved. The draft guidance suggests reviewing another guidance: Draft Guidance for Industry: Investigational New Drug Applications (INDs) –Determining Whether Human

Research Studies Can be Conducted Without an IND1, which when finalized will represent FDA’s current thinking on this topic. Similarly, with device studies, the IRB must review studies that do not have an IDE to determine whether they are appropriately categorized as non-significant risk or exempt by a sponsor. The draft guidance indicates that the FDA is available to assist sponsors, investigators and IRBs in making NSR or SR determinations, and suggests review of the guidance Procedures for Handling Inquiries Regarding the Need for an Investigational Device Exemptions Application for Research Involving Medical Devices2 for information on how to request assistance.

The draft guidance proposes some flexibility for IRBs in evaluating investigators and proposed research sites in circumstances where the IRB is familiar with the institution and/or investigator and the nature of the study does not warrant additional scrutiny. As to the IRB determination of necessity of an IND or IDE, the FDA re-iterates the IRB’s responsibility of evaluating a sponsor’s determination as to whether the IND or IDE regulations apply to a particular study. The draft guidance indicates that FDA expects the IRB to obtain and evaluate an explanation as to why the sponsor would not seek an IND or IDE for research involving FDA-regulated products.

Comments on the draft guidance were due January 22, 2013. To see the proposed draft Guidance, please visit www.regulations.gov.

1 Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM229175.pdf .

2 Available at: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm126598.htm.

January 29, 2013 | Volume 3, Issue 1

Screening Subjects: To Consent or Not?

Quorum frequently receives questions from investigators and study staff about whether a consent form is necessary for the screening process for a given study. The FDA has issued guidance on this question, indicating that informed consent must be obtained prior to initiation of any clinical procedures that are performed solely for the purpose of determining eligibility for research.1

The FDA provides some examples of “procedures” that could be performed solely for the purpose of determining research eligibility, such as: withdrawal from medication (or wash-out) and diagnosis or treatment of a disease or medical condition.

Because clinical screening procedures for research eligibility are considered part of the subject selection and recruitment process, the FDA indicates they require IRB oversight, and recommends that the IRB receive the following information regarding the screening process that will be conducted by an investigator:

An outline of the screening procedure to be followed

A description of how consent for screening will be obtained

A screening consent form including a brief summary description of the study in which they may be asked to participate OR request for a waiver of consent for the screening procedures (if appropriate)21

1 FDA Information Sheet, Screening Tests Prior to Study Enrollment, available at: http://www.fda.gov/RegulatoryInformation/Guidances/ucm126430.htm , accessed 12/26/2012.

2 Id.

A common scenario, as part of screening for a clinical trial, is an individual patient being asked to fast prior to coming in for a visit. If that individual would not otherwise be asked to fast for their clinic visit, they should be consented before they are asked to fast. This request may occur over the phone, and therefore the researcher is not able to obtain a signed consent form prior to requesting that the patient be fasting when they come in for their next visit.

In this scenario, the researcher can request that the IRB waive the requirement for a signed consent form. This is also known as a

“waiver of documentation of consent.” The criteria that must be met in order to waive documentation of consent are defined in the FDA and HHS regulations as follows:

“The IRB may, for some or all subjects, waive the requirement [of a] sign[ed] written consent form if it finds that the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context.”3

Although a screening procedure or processes may qualify for a waiver of documentation of consent, the IRB can still require that the investigator provide individuals with a written statement regarding the research. In the case of a phone-based consent process for screening procedures this may be a

3 45 CFR 46.117(c)(2); 21 CFR 56.109(c)(1).

January 29, 2013 | Volume 3, Issue 1

Although a screening procedure or processes may qualify for a waiver

of documentation of consent, the IRB can still require that the investigator provide

individuals with a written statement regarding

the research.”

“

statement that is read to subjects over the phone, often described as a “screening” or “receptionist” script. Typically, the IRB would require the elements of consent to be covered in this statement.

The FDA has also provided guidance covering oversight of the use of such scripts. Specifically, the FDA has identified several issues that are appropriate for an IRB to consider when evaluating the use of a script for screening purposes:

• A description of what happens to personal information if the caller ends the interview or simply hangs up

• Whether the data is gathered by a marketing company

• How the data will be used, if it is sold, etc.

• Whether names of non-eligible individuals are maintained in case they would qualify for another study

• How paper copies/records related to the screening are handled (shredded, readable copies put out as trash)1

Generally, Quorum would recommend sites develop a standard operating procedure (SOP) or other policy document describing the use of screening scripts and addressing the points of concern outlined by FDA when a screening script is used.

Contact Quorum Review

Interested in learning more about Quorum Review?

Our Institutional Team is ready to answer your inquiries regarding your organization’s specific institutional IRB needs.

Nancy Jane Earnhardt Institutional Specialist nearnhardt@quorumreview.com T | 919-930-5198

The Institution Bulletin is a special publication of the Quorum Forum, and brought to you by the Institution Team at Quorum Review IRB.

1 FDA Information Sheet, Recruiting Study Subjects, available at: http://www.fda.gov/RegulatoryInformation/Guidances/ucm126428.htm, accessed 12/26/2012.