Dominic Chiarelli

by Dominic Chiarelli

Research Using Human Specimens and Data

The use of specimens and data from human subjects to answer research questions is often critical to advancing biomedical research and the goal of improving patient outcomes. Despite its importance and its prevalence, most investigators are mystified by the different ways in which research with specimens and data may be regulated under the federal landscape for human subjects protection. The answer, which perhaps is surprising, is that it often depends on the choices made by the investigators themselves.

Let us show you what we mean. . .

 

Department of Health and Human Services (“HHS”) Regulations

The HHS regulations for the protection of human subjects were promulgated with the use of human specimens and data for research in mind. Two points of flexibility were purposefully built into the regulatory landscape to provide investigators with the opportunity to adopt a research design that does not require formal IRB review or obtaining prior informed consent.

 

Definition of Human Subjects

The first point of flexibility is the definition of human subject – a living individual about whom an investigator conducting research obtains data through intervention or interaction with the individual, or identifiable private information.[1] Private information includes specimens as well as anything else that has been given for a specific purpose and in which it is reasonable to expect that it will not be made public. The flexibility comes with the requirement that the private information must also be identifiable in order for its use to be considered one involving a human subject. This means the investigator cannot know nor have the ability to know the identity of the individual. This is a low bar, but it does afford some flexibility. For example, research involving specimens and/or data provided from a biobank, even if labeled with a re-identification code, can usually be determined to not meet the definition of human subjects and therefore a research activity that does not require IRB oversight and the need for prior informed consent. To learn more about biobanking’s US and Canadian legal environment, see Quorum Review’s webinar Biobanking and Future Research: Addressing the Unknown in Protocol and Consent.

 

Exempt from the Regulations

The second point of flexibility is the regulatory exemption for research that only involves using specimens and data from human subjects – research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects [2]. The flexibility here is that the investigator may know or be able to know the identity of the individuals, but if the specimens and data as used for the research do not in-and-of-themselves allow for identification the research may be determined to be exempt from IRB oversight and the need for prior informed consent. This exemption potentially offers a lot of flexibility if implemented correctly. For example, it allows for the review and abstraction of information from detailed medical records as long as identifiable information stays in the medical record and remains out of the data collection form – sex, diagnosis, treatment, and health status are all allowable. It’s even allowable to take an identifier that is necessary to answering the research question and change it into a non-identifier, for example changing date of birth to age in years. A researcher can also take specimens or data that have been collected for their own biobank and use them without identifiers or links to identifiers and stay within this exempt criteria. There is, however, one significant caveat. All specimens and data for this type of research must be currently available (on the shelf) at the time the research is determined to be exempt. This is true even if the material would be collected regardless of the research.

 

Food and Drug Administration (“FDA”) Regulations

The FDA regulations concerning IRB review of clinical investigations have their own unique definition for research and human subjects[3]. These regulations offer less flexibility when they apply, but they often do not apply in the context of research involving specimens and data only. The key considerations are whether the intention of the investigation is to assess the safety or effectiveness of a medical device, usually an in vitro diagnostic, or whether the results of the investigation are intended to be held for or submitted to the FDA as part of a research or marketing application. With regards to the first consideration, the FDA has in fact issued guidance stating that they will exercise enforcement discretion and not apply their regulations requiring informed consent for in vitro diagnostic research using left over specimens that are not individually identifiable[4] . It is important to note that IRB review and approval is still required in this context, but consent may not be.   The second consideration is completely within the control of the investigator and offers some flexibility in that investigators can and should know their intentions when designing a protocol and should make these intentions as clear as possible within the protocol and to any reviewing IRB.

 

It takes planning to leverage regulatory flexibility

While, and perhaps because, the regulations provide flexibility for research involving the use of specimens and data, investigators tell us that this can be one of the more complex and confusing aspects of human subjects research. Despite this complexity, with a little early planning and IRB coordination it is common that researchers can structure their study protocols to forgo formal IRB review and the necessity of prior informed consent. To help them plan their research, clients often use our human research and exempt determination request form as an instruction manual to the regulatory flexibility that is available. The form is broken into non-human subjects and exempt sections and clearly identifies the parameters that determine how a research protocol should be considered. In addition, many clients rely on Quorum’s industry leading team of regulatory attorneys who enjoy working with investigators to help them understand the regulatory landscape and the choices at their disposal. If due to research constraints all else fails, Quorum also offers a simplified questionnaire for single-site research-retrospective chart review for situations that cannot take advantage of the regulatory flexibility and required formal IRB review.

 


 

 

References

[1] 45 CFR §46.102(f)
[2] 45 CFR §46.101(b)(4)
[3] 21 CFR §56.102
[4] See 21 CFR part 50 and IVD Guidance