- Background and Rationale: Balancing Privacy Concerns with Advancing Technologies
- Definition and Overview of Broad Consent Requirements
- Definition and Description of Identifiable Information or Biospecimens
- Time Period for Storage and Use
- Disclosure of Future Users
- Commercial Use of Data
- Disclosure of Future Use
- Participant Perspectives
The rapid increase in biospecimen repositories and the ability to link this data with integrated administrative datasets are continuing to influence how potentially identifiable participant information and biospecimens are collected and shared across research, healthcare, educational, and criminal justice systems. At the potential cost of individual privacy, aggregating data requires identifying individuals across datasets and has several benefits. Often undetected by smaller, lower powered studies, large aggregated datasets provide a cost-effective method to identify complex associations between biology and environmental risk factors for poor outcomes. However, these integrated datasets require additional confidentiality protections both because researchers may need to utilize legitimate means of identifying and linking an individual’s information across datasets and the increasing sophistication of individuals within and outside the research community to re-identify assumed protected de-identified information (Fisher 2017c, Homer et al. 2008, Lunshof et al. 2008).
The introduction of broad consent in federal regulations arose in response to these concerns as well as recognition that additional participant protections were required for the long-term secondary use of potentially identifiable information by investigators who were not involved in the original collection of data and who might use the data for research purposes significantly different from the original study to which participants consented. Prevention scientists planning to store and maintain potentially identifiable information and biospecimens for future use by other researchers may substitute broad consent for the traditional consent procedures as long as the broad consent includes the components described in the next section and the reasonable person standard discussed above.
Background and Rationale: Balancing Privacy Concerns with Advancing Technologies
How to protect the autonomy of participants without hindering an important avenue of research and discovery has been vigorously debated in recent years (Berkman et al. 201, Grady 2017, Grady et al. 2015). Under previous regulations, investigators wishing to use secondary data could re-consent participants from the original study, or more commonly, petition the IRB to waive consent for secondary use (OHRP 2017). The Final Rule recognizes that re-consent is potentially a costly, burdensome, and prohibitive process which may not only derail promising scientific advances but may introduce unnecessary risk of privacy violations during re-identification procedures. However, the new' regulations also attempt to address instances in which waiver of consent for secondary analysis may lead to similar privacy risks and potential violations of participant autonomy. Broad consent is a regulatory attempt to achieve an appropriate balance between participant rights to determine the future use of their research data and the scientific benefits that may accrue w'hen such use involves unspecified investigators and research aims.
Definition and Overview of Broad Consent Requirements
According to the new regulations, as part of the initial consent procedures, investigators may seek broad consent for the storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens collected for studies other than the initially proposed research or for non-research purposes
(§_.116(d); OHRP 2017, p. 7265). When compared to the practice of obtaining a
waiver of re-consent for secondary analysis, broad consent increases transparency and provides greater opportunities for participants to decide if their identifiable private information or identifiable biospecimens may be used by future researchers for specified or unspecified research purposes (Menikoff et al. 2017). When broad consent is obtained, future research covered by the broad consent may be subject to limited IRB review' designed only to determine if the proposed research is w'ithin the scope of the broad consent. IRB waiver of consent to use previously collected data for secondary use remains an option under the Final Rule. However, if broad consent has been offered but refused, an IRB cannot waive consent for secondary research use of that person’s identifiable private information or identifiable biospecimens.
The regulatory vision for broad consent for future research hinges on the extent to which participants are provided with details of the nature, storage, maintenance, and future uses of their identifiable data needed for the reasonable person to make an informed decision. To be sufficiently robust, the regulations mandate a series of information disclosures related to the type of data stored, time period for storage and use, types of future use, and with whom data may be shared. Mandates also include additional disclosures related to whole-genome sequencings, clinically relevant data, and when data may be de-identified or glean commercial profit. A discussion of the required disclosures is provided below.
Definition and Description of Identifiable Information or Biospecimens
A significant change in the Final Rule is the inclusion of “identifiable information
and biospecimens” under the definition “human subject” (§__.102 (e) 1 (ii); OHRP
- 2017). This expanded definition has been quite controversial since it means that identifiable information and biospecimens require the same protections as persons. Since the Final Rule requires investigators to describe the identifiable information and biospecimens that will be collected and stored for future use, it is noteworthy that the term identifiable is defined as “private information [or biospecimen] for which the identity of the subject is or may readily be ascertained by the investigator or associated with the information [or biospecimen]” (§__.102 (e) 5-7; OHRP
- 2017, p. 7260). The inclusion of “may readily be ascertained” is in recognition of the evolving ability to re-identify previously de-identified genetic information. At present, what qualifies as an identifiable biospecimen is left to the discretion of the IRB, although the Final Rule includes a provision for convening a committee for periodic review of the definition. As a result, prevention scientists will need to keep abreast of continuously changing definitions of identifiable information and biospecimens for broad consent procedures. To date, the definition of sociodemographic identifiable information attached to biospecimens or as part of administrative systems linkages draws from the Health Insurance Portability and Accountability Act (HIPAA) and includes but is not limited to: name; place of birth and mailing address more specific than state residence; hospital admission or discharge date more specific than year; email, telephone, and fax; Social Security or health plan number (US Department of Health and Human Services 2012). The original participant ID number is also considered an identifier and will need to be recoded if data is defined as de-identified.
Time Period for Storage and Use
A second required component is the time period of storage and use of the identifiable data, which can be limited or in perpetuity. Determining and communicating a time period for data use is particularly relevant when working with members of American Indian Alaskan Native (AIAN) nations. Some tribal communities, such as the Havasupai, prohibit body fragmentation and biospecimens living outside the body or after death (Bardill and Garrison 2015, Pearson et al. 2014, Sahota 2014). Broad consent for AIAN populations should, therefore, consult with AIAN leaders and carefully specify conditions for storage, destruction, and blessing before destruction of biospecimens (Arbour and Cook 2006). Extended time periods for storage also have implications for biospecimens collected on minors with guardian permission. Investigators must consider whether child participants, when they become legal adults, will be notified as to where their biological materials are stored and conditions in which they will or will not have a right to re-consent or withdraw permission for further use of their data (Fisher et al. 2013). When unlimited time periods for data storage and use conflict with cultural values or rights of minors, investigators may consider a model of “DNA on loan” where donations remain the property of the participant who gift their biospecimen to researchers who agree to act as faithful stewards for a specific period of time and for a specific research project (Arbour and Cook 2006).
Disclosure of Future Users
Broad consent must disclose who may have access to a participant’s stored identifiable data or clearly indicate that the identity of those with access to secondary use will remain unspecified. Most commonly, access will be limited to investigators affiliated with accredited universities, research, or medical institutions that have the institutional oversight and infrastructure to adequately protect data security and abide by restrictions on use outlined in the broad consent. When considering whether to conduct secondary research or deposit data into biobanks or other data repositories, prevention scientists should investigate whether the repository conforms to applicable regulations and policies. The University of California (2012) has an informative guide to evaluating biorepositories that includes but is not limited to procedures for: (1) identifying and ensuring that the aims of secondary usage requests are consistent with consent obtained from participants; (2) evaluating the qualifications of researchers and entities requesting access to data; (3) updating data security in response to emerging technologies; (4) including a submittal agreement from the original investigator attesting to the IRB approval and written informed consent of participants from whom data was collected; (5) providing a standard usage agreement that details conditions for receipt and future use of data or human specimens; and (6) continuing committee review and oversight.
Commercial Use of Data
The movement toward open science, including the availability of data from prevention trials to other scientists and stakeholders (Caulfield et al. 2012, Leadbeater et al. 2018) and growing interest in genetic responsivity to psychopharmacological medications for behavioral and other mental health disorders is likely to be paralleled by increased interest in secondary use of biobank data by pharmaceutical companies and in funding prevention scientists to conduct such research. As recommended by the SPR Ethics Task Force (Leadbeater et al. 2018), investigators need to disclose financial and professional conflict of interests to all stakeholders, especially when presenting the scientific findings to stakeholders that affect program adoption, dissemination, and implementation strategies.
The new broad consent regulations require disclosure to participants if their biospecimens may be used for commercial profit, and whether they will receive any portion of these profits. To be in compliance, at the outset of commercial sponsor funding relationships, investigators need to: (1) reach an agreement on where data will be stored; (2) ensure data repositories meet current standards of informational security if deposited at a company facility; (3) have a clear understanding of which entity owns the data for future use; (4) whether such use will be for commercial profit; and (5) whether participants will receive any portion of these profits.
Disclosure of Future Use
A fourth requirement of broad consent is a mandate to disclose how participants’ identifiable information may be used, whether whole-genome sequencing may be conducted by other investigators, whether participants will be informed of future use, and if they are being asked to agree to future research that may not be aligned with the purpose of the original study. Although investigators are not required to return individual genomic results to participants, survey research indicates that genetic testing serves as a strong incentive for participation and individuals often prefer to be provided with incidental results that go beyond the original aims of the study (Kaufman et al. 2016). Ethical obligations for disclosure of clinically relevant genetic information uncovered during secondary analysis will increase as genetic research advances to adequately identify and successfully intervene to reduce vulnerability or enhance development for critical outcomes such as academic achievement, health, and well-being (Appelbaum et al. 2014, Fisher 2006b, Grandjean and Sorsa 1996, Jarvik et al. 2014, Ravitsky and Wilfond 2006). Broad consent must thus include a statement regarding whether participants will be informed of clinically relevant findings that may emerge.
Emerging empirical evidence on public willingness to provide broad consent or donate genetic information to biobanks for future research suggests that a majority of people are willing to consent for altruistic reasons if adequate privacy protections are in place, they are informed about who will use the data, and have a say in how their information will be used (Burstein et al. 2014, Hens et al. 2011, Kaufman et al. 2008, 2016, Lemke et al. 2010, McGuire et al. 2008, 2011, Oliver et al. 2012). However, willingness to consent varies by the type of future research and the background of the prospective participant. According to one survey study, participants willing to donate biospecimens for future disease-related research were more hesitant on its use for socially sensitive topics such as abortion, genetic influences on violence, or vaccines related to biological weapons (De Vries et al. 2016). In a survey on adults’ opinions about a nationwide precision medicine initiative involving collection of genomic and environmental information, fewer respondents were willing to agree to the use of their data with researchers outside of the United States or pharmaceutical or drug companies than with American academic researchers or NIH researchers (Kaufman et al. 2016).
The perceived vulnerability of participants has also been shown to influence willingness to share DNA samples for future research. In several studies, parents providing broad consent for their minor child expressed concern about unknown future risks and future decision-making for themselves and for their children when their children become adults (Burstein et al. 2014, Hens et al. 2011, Kaufman et al. 2008). In one of the few studies examining youth attitudes, adolescents who were receiving outpatient oncology, cardiology, and orthopedics services were more willing to donate their specimens to biobanks than their parents or their healthy peers (Kong et al. 2016). In a large nationally sponsored epidemiological study on mental health and substance use, although donation rates were high overall, African Americans and individuals with less education and a history of drug abuse were less likely to consent to sharing their sample with other investigators (Storr et al.
2014). Attitudes toward collection, storage, and use of biospecimens may also differ by culture and social risk factors. For example, community members in Africa, Asia and the America’s involvement in HIV prevention trials, indicated that in some instances, sexual partners and spouses of participants wanted information on where biospecimens would be stored and to be included in decision-making (MacQueen and Alleman 2008).
The public response to the expansion of genetic explanations for substance use, behavioral disorders, racial/ethnic differences in mental health, and other socially stigmatized behaviors has the potential to perpetuate health disparities by attributing vulnerabilities intrinsically tied to social and structural inequities to genetic characteristics (Fisher et al. 2013, Fisher and McCarthy 2013). The extent to which unspecified secondary use of biospecimens can pose a social risk to already vulnerable populations is difficult to anticipate or describe in broad consent procedures. Because participants may be unwilling to provide a blanket broad consent for future use of their specimens, prevention scientists may consider allowing participants to opt out of use of their data for specific future research purposes. This approach may, however, place unrealistic demands on researchers to identify all possible future uses and if not adequately specified, place an unachievable burden on IRBs to interpret whether proposed secondary research aims meet the original broad consent specifications. One solution is to engage community advisory boards in creating explicit opt-out procedures tailored to the unique characteristics of participant populations to create a goodness-of-fit between broad consent procedures and participant values and concerns (Fisher 2015, Fisher and Ragsdale 2006).