Attachment A to January 24, 2011 SACHRP Letter to the Secretary

FAQs, Terms and Recommendations on Informed Consent

and Research Use of Biospecimens

The Secretary’s Advisory Committee on Human Research Protections (SACHRP)

October 19, 2010[1]

Preface 

The collection and use of human specimens have become essential to biomedical research.  These biospecimens include blood and other tissues, some collected originally for clinical lab tests, some removed during surgeries, and some obtained specifically for research.  While there is no accurate catalog of the number or locations of specimens, there are reasonable estimates that billions of specimens are now stored in laboratories, repositories and “tissue banks” across the country.  Coupled with associated clinical data and the power of bioinformatics, these specimens represent an invaluable resource for current and future research on human health and disease.

At the same time, there are significant ethical, legal and social policy implications relating to the collection, storage and use of biospecimens.  Institutions, investigators, institutional review boards (IRBs), funding agencies and the public are struggling with issues like informed consent, ownership, stewardship, genetic testing, and future uses that are often unspecified at the time specimens are first obtained.  The ethical tensions that frequently exist between the needs of science and the rights of individuals are present in research involving specimens, and there is much inconsistency and uncertainty as to how they should be used responsibly.  The research community would benefit from federal-level guidance. 

The Secretary's Advisory Committee on Human Research Protections (SACHRP) has considered a number of unanswered questions relating to informed consent and research use of biospecimens.  Upon request by SACHRP, the Subpart A Subcommittee of SACHRP deliberated on these issues and presented their recommendations to SACHRP for further discussion and approval, over the course of several meetings in 2009 and 2010.  The finalized recommendations take the form of a series of "Frequently Asked Questions" (FAQs), each presented as a commonly-encountered scenario and a suggested response that addresses regulatory and ethical issues.  The goal was to provide a framework for IRBs, institutions and investigators to consider individual research scenarios without proscribing the final outcome, recognizing that those decisions will always be case-specific.

It is hoped that these compiled FAQs and recommendations constitute a product that the Office for Human Research Protections and others can use to provide much-needed guidance in this area.

I. Glossary and concepts

1. CODED[2] means:

            (1) Identifying information (such as name or social security number) that would enable the investigator to readily ascertain the identity of the individual to whom the private information or specimens pertain has been replaced with a number, letter, symbol, or combination thereof (i.e., the code); and

            (2) a key to decipher the code exists, enabling linkage of the identifying information to the private information or specimens.

2. HONEST BROKER means:

A neutral intermediary (person or system) between the individual whose tissue and data are being studied, and the researcher. The honest broker collects and collates pertinent information regarding the tissue source, replaces identifiers with a code, and releases only coded information to the researcher.

3. LIMITED DATA SET:

As defined by HIPAA, limited data sets are data sets stripped of certain direct identifiers that are specified in the Privacy Rule. They are not de-identified information under the Privacy Rule.

A limited data set is protected health information that excludes the following direct identifiers of the individual or of relatives, employers, or household members of the individual:  (1) names; (2) postal address information, other than town or city, State, and zip code; (3) telephone numbers; (4) fax numbers; (5) e-mail addresses; (6) social security numbers; (7) medical record numbers; (8) health plan beneficiary numbers; (9) account numbers; (10) certificate/license plate numbers; (11) vehicle identifiers and serial numbers; (12) device identifiers and serial numbers; (13) web URLs; (14) Internet Protocol (IP) address numbers; (15) biometric identifiers, including fingerprints and voiceprints; and (16) full-face photographic images and any comparable images.

Importantly, unlike de-identified data, protected health information in limited data sets may include the following: city, state and zipcodes; all elements of dates (such as admission and discharge dates); and unique codes or identifiers not listed as direct identifiers.

Recognizing that institutions, IRBs and investigators are frequently faced with applying both the Common Rule and the HIPAA Privacy Rule, OHRP does not consider a Limited Data Set (as defined under HIPAA) to constitute individually identifiable information under 45 CFR 46.102(f)(2). 

4. When is research with specimens not Human Subjects Research?2

OHRP does not consider research involving only coded private information or specimens to involve human subjects if the following conditions are both met:

    (1) the private information or specimens were not collected specifically for the currently proposed research project through an interaction or intervention with living individuals; and

    (2) the investigator(s) cannot readily ascertain the identity of the individual(s) to whom the coded private information or specimens pertain because, for example, there are agreements, IRB-approved policies and procedures, or legal requirements in place that prohibit the release of the key to the code to the investigators under any circumstances until the individuals are deceased.

II. Related SACHRP Recommendations

1. Recommendation on Compatibility of Secondary Use with Consent.

The determination of whether a proposed secondary research use is compatible with the original consent will be context-specific based on a range of considerations.  If the original consent form specifically prohibited the proposed research activity, it is presumed the research is not allowable. If the consent does not prohibit the proposed use, IRBs should consider several questions to determine compatibility:

• What is the nature of the proposed secondary research?
• Could it reasonably be understood to fall within the scope of research that was described in the original consent form?
• Does the new research use impose new or significantly greater risks (including privacy risks) not described in the initial consent form?
• Are there known concerns of the study population(s) about the proposed new use?

2. Recommendation on the Definition of “Investigator.”  

OHRP should revise its interpretation of who is considered an “investigator” in secondary use of coded information or specimens. Original collectors who are providing such information or specimens without identifiers should not be considered to be “investigators” involved in human subjects research, even if they are involved in analysis of aggregate data or publication of results, provided the secondary users are unable to readily ascertain the identity of subjects. Under such circumstances, neither party shall decode or re-identify subjects.

Mechanisms to support this interpretation could include (a) the presence of an agreement that prohibits release of the key from the original provider to secondary users; or (b) the existence of a repository or banking system that prohibits the secondary users from access to identifiers.  These same interpretations and mechanisms should be applied whether the original provider and secondary user(s) are within the same institution or at different institutions.

The intent is to support a conclusion that secondary uses under such circumstances do not constitute research involving human subjects (as defined under 45 CFR 46.102(f)) and therefore do not require IRB review and approval, in keeping with OHRP’s “Guidance on Research Involving Coded Private Information or Biological Specimens.”

III. Frequently Asked Questions (FAQs)

FAQ #1

Tissue biopsies were obtained for clinical diagnostic purposes, which have now been satisfied.  The hospital pathology department is willing to provide a portion of the remaining biopsy specimens to an investigator who will perform research assays.  In order to allow matching with relevant clinical information, the specimens will be provided with identifiers such that the investigator can readily ascertain the identity of subjects. 

Is consent of the patient from whom the biopsy was taken (or waiver of consent) required for the secondary research use?

Response. Yes.  Under this scenario, informed consent of the subjects should either be obtained or waived under 45 CFR 46.116(d) because the samples are identifiable to the recipient investigator.

HIPAA Issues. Assuming the hospital is a HIPAA covered entity, the use or disclosure of patient identifiers for the research purpose would also require a HIPAA authorization from the patient or a waiver of authorization by an IRB or Privacy Board.

FAQ #2  

Tissue biopsies were obtained for clinical diagnostic purposes, which have now been satisfied.  The hospital pathology department is willing to provide a portion of the remaining biopsy specimens to an investigator who will perform research assays.  The specimens will be coded such that the investigator will not be able to readily ascertain the identity of individuals. 

Is consent of the patient from whom the biopsy was taken (or waiver of consent) required for the secondary research use?

Response. No.  Under this scenario, neither consent nor waiver is required, because the activity is not considered to be research involving human subjects.

HIPAA Issues. If the information associated with the specimen is de-identified in accordance with the HIPAA Privacy Rule, neither authorization nor waiver of authorization is required, because it would no longer be considered Protected Health Information.

Note, however, that information associated with the specimen that is not individually identifiable per OHRP guidance    (i.e., coded) may not necessarily be de-identified for HIPAA Privacy Rule purposes.  For example, the coded information may not be considered to be de-identified under the Privacy Rule if the code is derived from a patient identifier or certain data elements, such as dates of service or zip codes, remain with the information.  Thus, the use or disclosure of the information for research may still require a form of HIPAA permission, such as a HIPAA authorization, IRB or Privacy Board waiver of authorization, or, if the information constitutes a “limited data set,” a data use agreement with the recipient of the information.

FAQ #3  

Blood samples were obtained for research purposes, with informed consent of the subjects, and the original study has been completed.  The samples remain under the control of the original investigator.  Another investigator wants to use a portion of the remaining samples to perform research completely unrelated to the original study.  

If the original consent stated that “…your sample will only be used for research on colon cancer,” but the secondary user is interested in studying Alzheimer’s disease, can the samples still be used if provided to the secondary user in a coded fashion?

Response. The secondary use of de-identified or coded samples is not research involving human subjects under 45 CFR 46. In the case where secondary use of tissue samples is not compatible with the original consent for tissues that are de-identified, coded, or anonymized and are not readily identifiable, the samples are no longer subject to human subject regulations. Thus, there is no regulatory violation. Nevertheless, the original investigator and his/her institution have made an agreement with the subjects about use of their specimens, and have an obligation to honor that agreement.

Institutions should establish mechanisms to determine whether secondary uses are compatible with the original informed consent; this could involve consultation with the IRB that approved the original research, or review by some other body designated for these purposes. Coding should not be used as a means to circumvent the original terms of consent. This is ethically problematic, even if the original project is over and the secondary use is no longer considered to be research involving human subjects.

FAQ #4

It is increasingly common to collect and store specimens for future unspecified research. How broad can this consent be without requiring investigators to obtain additional consent for specific uses?   Alternatively, how specific must this consent be to allow for future use of biospecimens? 

Response. There is a tension between the desire to be as specific as possible when informing subjects of what will be done, and the reality that specifics are, by definition, not known at the time of consent.

Many institutions and IRBs have found it prudent to be general enough in the consent form to give subjects a reasonable idea of the types of research that might be conducted in the future and the associated risks, but without placing unreasonable restrictions on what the research might be.  Thus, subjects can be informed that future studies may involve genetic research, drug development, or searching for links between genes and environmental factors like diet or lifestyle, or between genes and diseases.  While examples might be given of specific diseases (e.g., cancer, diabetes, heart disease), being overly-specific or restrictive in this regard may result in problems later, when investigators propose other uses.   IRBs and investigators should consider the downstream implications before promising subjects that “your specimens will only be used for research on XYZ.”

Future uses of identifiable specimens should be reviewed by the IRB, which should determine whether the research is compatible with original terms of consent, or whether additional consent may be required.

Alternatively, the creation of a repository with an oversight committee and “honest broker” mechanisms that distribute specimens to investigators in coded fashion can remove subsequent uses from IRB review, to the extent they no longer constitute human subjects research.  In these cases, special attention should be given upfront to ensure that the repository (which is human subjects research and does require IRB approval) is established with policies and procedures to effectively manage subsequent uses in keeping with what the IRB approved.

HIPAA Issues. This scenario raises a number of HIPAA-related issues for institutions that are covered entities under the Privacy Rule.

While consent under 45 CFR 46 can be broader than a specific research study, an authorization under the HIPAA Privacy Rule must be study-specific.  How specific must that authorization be?  How can health information associated with specimens be used and disclosed from a research repository when specific research uses are unknown at the time the information is collected?

There are two separate activities to consider when a HIPAA covered entity is collecting and storing identifiable health information in a research repository for future unspecified research:

(A) a covered entity’s use or disclosure of protected health information (PHI) to create the repository; and

(B) the release of PHI from the repository for a future research purpose.

There are a number of ways health information can move into and out of a research repository, including those established for future unspecified research. In this scenario, it is assumed that the repository will contain PHI and that authorization will be obtained to create it. With reference to the two separate activities in this scenario:

(A) An authorization for research use and disclosure of PHI under the HIPAA Privacy Rule must be study-specific.  However, the authorization may state that the purpose of the authorization is to create a research repository or database.

(B) Health information can then be subsequently used and disclosed from the research repository in one of several ways:

1. With study-specific authorization
2. With waiver of authorization by an IRB or Privacy Board
3. Preparatory to research (with certain representations)
4. Use of a HIPAA De-identified Dataset*
5. Use of a Limited Data Set (with data use agreement)
6. Research solely on decedents (with certain representations)

FAQ #5 

When can informed consent be waived for use of previously-collected human specimens and data (e.g., when does such research meet “minimal risk” criteria, what does “practicability” mean with regard to the informed consent waiver criteria)?

Response. The criteria for waiver of consent under 45 CFR 46.116(d) include that the research involves no more than minimal risk; the waiver would not adversely affect the rights and welfare of subjects; the research could not practicably be carried out without the waiver; and whenever appropriate, the subjects will be provided with pertinent information after participation.

Points to consider in applying these criteria include the nature of the research; the protections in place to maintain privacy and confidentiality (e.g., coding, limited/controlled access, honest broker mechanisms); the change in level of risk, if any; the ability to locate or contact subjects; risk of introducing bias into the research; potential anxiety or confusion for subjects; the number of subjects; the length of time since specimens were first collected; and the likelihood that subjects would object to the proposed secondary use, based on the nature of original collection.

FAQ #6 

Blood samples were obtained for research purposes, with informed consent of the subjects, and the original study has been completed.  The samples remain under the control of the original investigator.  Another investigator wants to use a portion of the remaining samples to perform research unrelated to the original study. 

If the sample is identifiable to the secondary user, is this considered to be human subjects research under the purview of the IRB?  If so, what are the consent considerations?

Response. Yes. This is human subjects research under the purview of the IRB.  The IRB should consider whether the secondary use is compatible with the original terms of consent given by the subjects.

HIPAA Issues. A HIPAA authorization for research must be research-study specific.  Thus, assuming a HIPAA covered entity is involved, a new HIPAA authorization would be required for the subsequent unrelated research use or disclosure, or another form of HIPAA permission obtained (e.g., waiver of authorization).

FAQ #7 

Identifiable blood samples were obtained for research purposes, with informed consent of the subjects, and the original study has been completed.  The samples remain under the control of the original investigator, who now wants to collaborate with another investigator to perform research unrelated to the original study. 

If the original consent was silent on the question of subsequent uses, is informed consent (or waiver of consent) required before the identifiable sample can be used for other purposes?

Response. Yes.  Under these circumstances, the IRB should consider the original terms of consent, and determine whether a waiver might be appropriate or whether additional consent is required.

The criteria for waiver of consent under 45 CFR 46.116(d) include that the research involves no more than minimal risk; the waiver would not adversely affect the rights and welfare of subjects; the research could not practicably be carried out without the waiver; and whenever appropriate, the subjects will be provided with pertinent information after participation.

Points to consider in applying these criteria include the nature of the research; the protections in place to maintain privacy and confidentiality (e.g., coding, limited/controlled access, honest broker mechanisms); the change in level of risk, if any; the ability to locate or contact subjects; risk of introducing bias into the research ; potential anxiety or confusion for subjects; the number of subjects; the length of time since specimens were first collected; and the likelihood that subjects would object to the proposed secondary use, based on the nature of original collection.

HIPAA Issues. A HIPAA authorization for research must be research-study specific.  Thus, assuming a HIPAA covered entity is involved, a new HIPAA authorization would be required for the subsequent unrelated research use or disclosure, or another form of HIPAA permission obtained (e.g., waiver of authorization).

FAQ #8 

Patients undergoing surgery agree to donate any excess tissue (i.e., beyond that needed for clinical purposes) to a tissue bank.  The creation of the bank has been reviewed and approved by the IRB, meaning the IRB has approved the policies and procedures under which the bank will be managed, the control of specimens, and the types of research to be conducted, etc .  The consent form makes it clear that the specimens and associated clinical data will be used for research, but does not specify or limit that use. 

If the bank employs an “honest broker” mechanism, so that specimens and any associated data are coded so that the recipient investigator cannot readily ascertain the identitybefore being given to investigators, is this subsequent use considered to be human subjects research under the purview of the IRB?

Response. No, the subsequent research use is not considered to be research involving human subjects and IRB review is not required.  However, there should be mechanisms in place to ensure that proposed research uses are compatible with the original consent.

HIPAA Issues. A HIPAA authorization for research must be research-study specific.  Thus, assuming a HIPAA covered entity is involved, a new HIPAA authorization would be required for the subsequent unrelated research use or disclosure, or another form of HIPAA permission obtained (e.g., waiver of authorization).

FAQ #9

Patients undergoing surgery agree to donate any excess tissue (i.e., beyond that needed for clinical purposes) to a tissue bank.  The creation of the bank is reviewed as human subjects research and approved by the IRB.  The consent form makes it clear that the specimens and associated clinical data will be used for research, but does not specify or limit that use. 

If specimens are provided to the researchers with clinical information that allows the researcher to readily ascertain the identity of the subjects, do those researchers need separate IRB approval of the proposed research use of the specimens and data?

Response. Yes, the provision of identifiable information with the specimen means the research to be conducted with the specimen is a separate human subjects research protocol and separate IRB approval would be required.

FAQ #10

Patients undergoing surgery agree to donate any excess tissue (i.e., beyond that needed for clinical purposes) to a tissue bank.  The creation of the bank is reviewed and approved by the IRB.  The consent form makes it clear that the specimens and associated clinical data will be used for research, but does not specify or limit that use. 

If specimens are provided to the researchers with clinical information that allows the researcher to readily ascertain the identity of the subjects, is a new consent from the patient/subject [or IRB waiver of informed consent] required?

Response. Yes, a new consent is required unless IRB determines that the original consent was adequate to allow the subsequent research use, or the IRB determines a waiver is appropriate.

The criteria for waiver of consent under 45 CFR 46.116(d) include that the research involves no more than minimal risk; the waiver would not adversely affect the rights and welfare of subjects; the research could not practicably be carried out without the waiver; and whenever appropriate, the subjects will be provided with pertinent information after participation.

Points to consider in applying these criteria include the nature of the research; the protections in place to maintain privacy and confidentiality (e.g., coding, limited/controlled access, honest broker mechanisms); the change in level of risk, if any; the ability to locate or contact subjects; risk of introducing bias into the research ; potential anxiety or confusion for subjects; the number of subjects; the length of time since specimens were first collected; and the likelihood that subjects would object to the proposed secondary use, based on the nature of original collection.

FAQ #11

An academic medical center has established a centralized tissue bank of specimens that it receives from a variety of sources.  The bank was reviewed as human subjects research and has IRB-approved policies and procedures in place.  These policies and procedures stipulate that the bank will release only coded specimens to researchers, without identifiers.

The institution now plans to begin moving excess clinical specimens to the bank in a prospective, ongoing manner, after their original purpose has been served.  The specimens would be identifiable going into the bank, in order to facilitate linkage back to clinical data.  Is this permissible if there was no research consent obtained from the patients?

Response. Because the excess clinical specimens are identifiable, this is human subjects research and consent would be required.  In rare circumstances, the IRB may determine that the conditions for a waiver of consent under 45 CFR 46.116(d) have been met.

Points to consider include governance and oversight of the bank; protections in place to maintain privacy and confidentiality (e.g. coding, limited/controlled access, honest broker mechanisms, de-identification processes, limited data use agreements); policies regarding access to specimens; the nature of the research for which the specimens may be used; the ability to locate or contact subjects; risk of introducing bias into the collection; potential anxiety or confusion for subjects; the number of subjects; the length of time since specimens were first collected; and the likelihood that subjects would object to the research use of their specimens.

FAQ #12 

A research participant agrees to allow extra blood to be stored for future research purposes.  Blood samples will be stored in a repository with identifiers. The participant later changes his/her mind.  Is this allowed, once tissue has been stored?

Response. Yes.  Subjects have the right to withdraw from research, and this extends to withdrawing their specimens from future research.  Subjects should be informed upfront about the procedures for withdrawing specimens from a repository. The obligation to honor subjects’ requests to withdraw does not extend to retrieving specimens already distributed to secondary users. Analyses already completed will generally not be destroyed or removed from datasets.  These practical limitations to withdrawal should be disclosed to subjects as part of the consent process.

HIPAA Issues. With respect to HIPAA authorizations, the HIPAA Privacy Rule provides an individual with the right to revoke an authorization in writing, except to the extent the covered entity has already acted in reliance on the authorization.  For example, a covered entity is not required to retrieve information that it disclosed under a valid authorization before receiving the revocation.  Thus, if a covered entity obtained an individual’s authorization to disclose identifiable health information to a repository, then the covered entity is not required to seek the return of the information.  Further, for research conducted by a covered entity, the reliance exception would permit the continued use or disclosure of PHI by the covered entity already obtained pursuant to the authorization to the extent necessary to protect the integrity of the research.

FAQ #13 

A research subject agrees to allow extra blood to be stored with identifiers for future research purposes. The individual later changes his/her mind and requests that the specimen be destroyed.  The lead investigator who manages the repository proposes to the IRB that, rather than losing valuable specimens, all identifiers and coding be permanently removed, so that it would be impossible for anyone ever to link to this subject’s identity; doing so would mean that any subsequent uses are not human subjects research, per OHRP guidance. 

Is this an acceptable approach?

Response. While it is true that permanently stripping a specimen of all identifiers or codes would mean that subsequent uses are not considered to be human subjects research, doing this after the fact would not be acceptable, if done solely to avoid withdrawing specimens on request. If the specimen is identifiable at the time of the request, failing to follow through when it is possible to do so would violate the ethical principle of respect for persons, and possibly the terms of original consent.

FAQ #14 

An investigator collected specimens from a large number of cancer patients and stored them with identifiers.  Some of the patient-subjects are now deceased. 

Is research using the specimens of those subjects who died still considered to be human subjects research, and under the oversight of an IRB?

Response. No.  45 CFR 46.102 defines a human subject as a “living individual.” However, deceased individuals would still have protections under the HIPAA Privacy Rule.

HIPAA Issues. The Privacy Rule generally protects the Protected Health Information of decedents in the same manner as that of living individuals.  However, in the research context, the Privacy Rule allows the use or disclosure of decedent information without the authorization of a personal representative and without waiver of authorization by an IRB or Privacy Board if the covered entity receives representations from the researcher that the decedents’ protected health information is necessary for the research and is being sought solely for research on decedents (and not related living individuals) and, upon request of the covered entity, receives documentation of the deaths of the individuals.

FAQ #15 

An investigator who collected and stored identifiable specimens accepts an offer at another institution, and plans to move the specimens with identifiers to the new institution. 

What are the issues that the IRB and/or institution should consider, when faced with this situation?

Response. This is an institutional responsibility that may involve multiple components across the institution, including legal counsel, sponsored programs, and the IRB, as appropriate.  The IRB’s role could include determination as to whether the transfer and use of specimens at the new institution is compatible with the consent under which the specimens were collected, whether additional consent may be required, or whether there are concerns relating to the communities or populations represented by the specimens.

Beyond these IRB-related considerations, other institutional policies will need to be considered.  Formal agreements should be established that govern the transfer of specimens from the institution that provides the specimens to the investigator and/or receiving institution. These agreements should specify as appropriate the rights and obligations of both the provider and the recipient, including intellectual property terms and publication rights, as well as the rights of subjects (e.g., whether subjects would have the ability to withdraw specimens once they pass to the new institution).

Similar considerations at the receiving institution would apply, including the need for IRB review of proposals for ongoing use of identifiable specimens.  

HIPPA Issues. If the institution is a HIPAA covered entity, then the institution also needs to consider whether the transfer of information from it to another entity was encompassed in the original HIPAA authorization or waiver of authorization, or if another HIPAA permission applies.

FAQ #15b 

An investigator who collected and stored specimens accepts an offer at another institution, and plans to move the specimens without identifiers to the new institution. 

What are the issues that the IRB and/or institution should consider, when faced with this situation?

Response. This is an institutional responsibility that may involve multiple components across the institution, including legal counsel, sponsored programs, and the IRB, as appropriate.  The IRB’s role could include determination as to whether the transfer and use of specimens at the new institution is compatible with the consent under which the specimens were collected or whether additional consent may be required,  or whether there are concerns relating to the communities or populations represented by the specimens.

Because specimens are being transferred without identifiers, subsequent uses would not be considered to be research involving human subjects under 45 CFR 46.

Beyond these IRB-related considerations, other institutional policies will need to be considered.  Formal agreements should be established that govern the transfer of specimens from the institution that provides the specimens to the investigator and/or receiving institution. These agreements should specify as appropriate the rights and obligations of both the provider and the recipient, including intellectual property terms and publication rights, as well as the rights of subjects.

FAQ #16 

A clinical trial is funded by an industry sponsor or other entity and the contract provides for specimens to be transferred to the sponsor or other entity. 

What factors should be considered in such an arrangement?

Response. The consent form should describe the plan to transfer specimens to the company or sponsor. Material Transfer Agreements (MTAs) or other similar legally binding agreements should be in place that describes the rights and obligations of the providing researcher and institution and the industry sponsor.  These should include stipulations that the use of the specimens will be compatible with the terms of the consent form and the approved protocol.

FAQ #17

The protocol for a clinical trial stipulates that all samples should be destroyed after the study is completed.  The consent form is silent on the disposition of samples after the study. 

What should be done if there are 10,000 identifiable specimens and new science becomes available?

Response. The investigator could amend the protocol, describing the circumstances and seeking IRB approval to retain the specimens for additional research. The IRB should consider if this additional research is compatible with the original terms under which samples were obtained.

FAQ #18

A tissue biopsy was obtained for clinical diagnostic purposes, which have now been satisfied.  The hospital pathology department is willing to provide a portion of the remaining biopsy specimen to an investigator, who will perform research assays with no clinical relevance.  If the specimen is coded and identifying information is removed so that the identity of the patient cannot be readily ascertained by the investigator before it is provided to them (so that it is de-identified for the purposes of HIPAA), is the investigator conducting human subjects research under the purview of an IRB?

Response. No, this is not research involving human subjects, because the recipient investigator will not be able to readily ascertain the identity of patients from whom specimens were obtained.

FAQ #19 

A tissue biopsy was obtained for clinical diagnostic purposes, which have now been satisfied.  The hospital pathology department is willing to send a portion of the remaining biopsy specimen to an investigator, who will perform research assays.  If the specimen will be provided to the researcher in an identifiable manner, is this considered to be human subjects research under the purview of an IRB?

Response. Yes, this is human subjects research.  Because investigators will receive a specimen with identifiable information, the research is non-exempt human subjects research that is nevertheless potentially eligible for expedited review.

FAQ #20 

Many hospitals have a sentence on the standard admission form to the effect that “This is a teaching and research institution, and any specimens remaining after your care is complete may be used for teaching or research purposes.”  Is this sufficient to allow identifiable specimens to be used for research purposes, without any additional consent or waiver?

Response. No, an additional consent or waiver is required. If the information provided to prospective subjects is limited to the above statement, this would not be sufficient to meet the requirements of informed consent for research under 45 CFR 46.  However, the IRB should review each protocol that proposes to use such specimens and, as part of that review, consider whether the criteria for a waiver of informed consent have been met at 45 CFR 46.116(d).

HIPAA Issues. This approach (single sentence on the hospital admission form) would also not be sufficient for HIPAA authorization purposes.

FAQ #21 

Many hospitals have a sentence on the standard admission form to the effect that “This is a teaching and research institution, and any specimens remaining after your care is complete may be used for teaching or research purposes.”  Is this sufficient to allow identifiable specimens to be placed into a tissue bank, if they are coded and released to researchers through an honest broker mechanism?

Response. The plan to remove identifiers from the specimens and manage them through a bank might be factors the IRB considers when assessing the risks to subjects, but it doesn’t change the fundamental answer above (FAQ #23). The creation of a bank containing identifiable specimens would be considered human subjects research and thus, subject to IRB review and informed consent.  As above, the statement on the admission form would not be considered sufficient to meet the requirements of informed consent under 45 CFR 46. However, the IRB could consider whether the criteria for waiving or altering informed consent have been met at 45 CFR 46.116(d).  The subsequent research use of specimens would not be considered human subjects research if the conditions of the OHRP guidance on coded private information or biological specimens have been met.

FAQ #22 

A 13-year-old child is enrolled by his/her parents in a tissue banking protocol that involves storage of specimens for future research.  Is the child’s assent required at the time of the original enrollment in the repository, in addition to parental permission?

Response. Yes, if the IRB determines that the children are capable of providing assent, taking into account the ages, maturity and psychological state of the subjects [45 CFR 46.408(a) and 46.116].   Given that most projects that store tissues for future unspecified research are not likely to hold out a prospect of direct benefit that is important to the health or well-being of the children and is available only in the context of the research, it is anticipated that affirmative agreement on the part of the child would generally be required.

FAQ #23 

A child is enrolled by his/her parents in a tissue banking protocol that involves storage of specimens for future research.  Should there be a process in place for the child to give consent for continued storage and use of specimens when he/she turns 18?

Response. In and of itself, the retention of specimens in a biobank is not considered to be research involving human subjects. However, ongoing use of such specimens (e.g., continued analysis of specimens or data for which the subject’s identity is readily identifiable to the investigator(s)), or ongoing collection of identifiable information, is human subjects research.  In these cases, it would be necessary for the investigator(s) to seek and obtain the legally effective informed consent of the now-adult subjects.

The IRB may consider, if appropriate, a waiver under 45 CFR 46.116(d) of the requirements for obtaining informed consent in order for the subjects to continue their participation in the research. Such a waiver may be considered at the time of initial review or during a subsequent amendment. Factors that may make it impracticable to conduct the research, and therefore would support a waiver, include the number of subjects, length of time since first enrolled, and ability to locate subjects (see also FAQ #5).

HIPAA Issues. A valid HIPAA authorization signed by a parent, as the personal representative of a minor child at the time the authorization is signed, remains valid until it expires or is revoked, even if such time extends beyond the child’s age of majority.  However, if the authorization expires on the date the minor reaches the age of majority, a new authorization (or other HIPAA permission) would be required at that time for continued use or disclosure of protected health information.

FAQ # 24

What issues should be addressed in the consent process with regard to sponsorship, ownership, control, access, commercialization and possession of stored specimens?

Response. Consent documents for such projects should disclose sponsorship and address issues including (but not limited to) disposition of samples, who will have access, how samples will be used, and the potential for commercialization, if any.  Subjects should be informed to what extent, if any, they can expect to control or receive compensation from future commercial uses.

Some of these matters are subject to state laws, and consent documents should reflect that.

As with any part of the consent form, care should be taken to communicate these complicated issues in simple terms understandable to the subject