CTSI Blogs

The Research Ethics Blog by Bernard Lo, MD

Research with Existing Data and Specimens: What if Participants Object?

The Havasupai, a Native American tribe living near the Grand Canyon, have a very high prevalence of diabetes.  Researchers collected blood samples and clinical data from 200 tribal members.  Discussions with the tribe focused on research with diabetes, but the consent form allowed the study “the causes of behavioral/medical disorders.” 

The researchers carried out a number of studies, including three genetic studies that tribe members found objectionable: on schizophrenia, on inbreeding, and on the evolution of populations.  The tribe regarded the first two studies as stigmatizing, and the latter study contradicted the tribe’s beliefs about their ancestry.  The tribe and individual donors of materials brought a lawsuit. 

After protracted legal procedures, in 2010 the university agreed to settle the suit, formally apologized, and agreed to return remaining blood samples to the tribe. Several of the researchers defended these studies as complying with federal research regulations and warned that the settlement could have a chilling effect on research with stored specimens. See article

Although this case involves a well-defined Native American tribe, it raises more general questions about broad consent for future research with biological specimens, which is frequently requested when specimens are obtained and does facilitate future studies. 


  • How can consent for collection of samples be improved, to take into account that some donors of materials might regard some future studies offensive, while not raising impeding important future research that cannot be anticipated at the time samples are collected? 


The most important consideration in this scenario is to be aware that this Native American tribe may have very different ways of viewing the world, university research and the consenting process. We already know that many mainstream community participants may have difficulty understanding exactly how research differs from standard medical care and may have problems understanding the jargon of research protocols. These problems may be exacerbated in a Native American population due to linguistic and cultural factors. It may also be the case that the tribe is not concerned with the same issues (i.e. schizophrenia, inbreeding or evolution of populations) the researchers find important. It would, therefore, be important to meet with tribal leaders to know what cultural and linguistic factors are relevant to the group. Additionally, researchers should have a thorough understanding of research questions the tribe deems would improve their quality of living. The tribe may already have culturally sanctioned ways of dealing with particular health issues and these responses to health concerns may or may not be compatible with the proposed research studies. Finally, we know that federal research regulations often do not fully cover ethical concerns. The fact that “several of the researchers defended these studies as complying with federal research regulations” makes me wonder how much knowledge they had of Native American culture broadly, let alone of this individual tribe. The disappointments that Native Americans have had with the actions and rules of the federal government are well documented and it is likely that only research that is well-planned with substantial input from the group will be meaningful.

This scenario highlights the difference between the legal and ethical responsibilities of researchers. While these researchers may have adhered to federal regulations, they did not take into account the potential difference in cultural values of the Native American group. In this specific scenario, the wording of the consent appears vague enough to give too great license to the researchers. Surely, at the time of collection, the researchers could have anticipated that they would examine such a common illness as schizophrenia, or concepts of inbreeding and evolution of populations among a small, isolated group. These issues do not appear to have been specified as best as possible for the informed consent of the Havasupai population. In terms of future use of stored samples, in the case of non de-identified information (that at least contains a cultural identifier), perhaps it would be prudent to review with the donating group any proposed research arising after collection of samples to ensure a re-informed consent is given. One might argue that not apologizing to the affected group and returning the blood samples would have a much more chilling effect on future research among the Native Americans and many other potential communities than would winning a lengthy legal battle to keep donated samples for future study.

I agree with Lawrence, there seems to be a fine line which becomes blurred when legality and ethics come into play. It is often that at risk groups are utilized for research purposes that purport to help that group in the long run.

Although I agree with many of the points of the first two commenters, I think there remains room to disagree. Although I agree that in this situation, the researchers may have overstepped their bounds from an ethical standpoint, I feel that a blanket prohibition on future research using current biobanked specimens without the express consent of the subjects who donated their samples would deal a significant blow to future avenues of research. I think that future research should be allowed to be conducted without express written consent of the subjects unless it deals in strict areas including substance abuse, mental illness, etc that can have a negative, stigmatizing impact on the group being studies even if their individual identities are preserved. It may make more sense to allow research on de-identified, banked specimens to occur without express written consent unless it involves these pre-specified sensitive subject areas including substance abuse, illegal activities (which would incorporate inbreeding as in this example), mental illness, etc. This may not solve all areas of cultural insensitivity that may arise (ie it wouldn't address areas of evolutionary history that the Native American tribe objected to), but it would mark a major step in the right direction.

The case of the Havasupai Indian tribe brings to the forefront the difference between what is legally acceptable and what is ethically acceptable. Because this group is a very specific demographic, one should not assume the same rules of informed consent as with another more general demographic. Indians have a long and complicated history in America and cultural issues play a part in what is considered ethical and appropriate. While it is true that normally an investigator would not need to get re-informed consent to run further studies on banked blood, these rules should have been re-examined by investigators in light of the population in question. The investigators should have considered the possibility that this group of people has a different belief system than the general american public. As mentioned in previous comments, investigators should have tried to be as explicit as possible with the original consent form to explain that blood might be used to study potentially stigmatizing conditions such as mental illness. In fact, even if we were not talking about the Havasupai Indians it would be prudent to explain this in detail in a consent form since for many people in the general community mental illness can be stigmatizing. One possible solution would be to make a good faith effort to track down the original study participants and ask them individually if they would agree to having further studies on schizophrenia and inbreeding done with their blood samples. Perhaps if investigators had asked permission from the community first and explained the goals of their studies, the participants would have been more likely to agree. It is always harder to ask for forgiveness than permission! If the participants or community refuses, then I think it would be appropriate not to do the studies since investigators have a moral responsibility to protect research subjects regardless of what is legal.

Earlier comments made a valuable point that differences in cultural belief systems are important in informed consent. However, I believe that the issues here are not so culturally distinct. I think many members of the more 'mainstream' american culture, even those very educated in the biomedical sciences, could empathize with the position of the members of this tribe. Imagine instead that you are the research subject. You have diabetes or your parent has diabetes, so supporting this research is meaningful for you. You sign a consent sheet that lists immediate risks and benefits, and the possibility of future secondary research on your sample. Now imagine that you pick up the newspaper the next year and find the researchers, having examined your sample from the diabetes study, have announced that your family has a (hypothetical) gene that shows a very high propensity to alcohol abuse and that your father is not actually your father. Whether you find this information distressing is highly personal, and it is quite possible you do not want such information being discussed by a larger community without your permission. I think the relevant issues here are not differing cultural cosmologies regarding blood and identity, but rather a legitimate sense of losing power over information about yourself and the people to whom you are connected. As mentioned by another commenter, the information about this tribe was not anonymous-for each individual yes, but not of the group as a whole. It identified who they were and dissected out their collective histories and identities for a bunch of strangers. I think the lack of anonymity is what is so unique about this particular case. In light of these concerns, an informed consent process should itemize the components, so that open ended secondary studies can be consented to independently of the primary study. This allows greater power to the subject and encourages further discussion between researcher and subject. A second suggestion is that in the case when groups are studied, efforts should be made to thoroughly anonymize the source of the samples, as you would with individual patients. The issue of the banked specimen here are that findings were identified with a distinct group of people, in a way that is more fundamental than, say banked neonatal blood of all californians. In the type of studies where such anonymity cannot be assured (e.g. when studying migration or evolution of a group) additional permission should be sought.

Researchers should explicitly state that “future studies have not yet been determined and may examine topics/diseases you could potentially find offensive.” The consent forms should include options such as “I wish that my blood be used by ASU researchers only,” or “I wish that my blood be used for the current study on diabetes only.” The informed consent discussion should also reinforce that the participant can withdraw from the study at any time and can request that his/her sample be destroyed at any time. Furthermore, because influential community leaders granted researchers access to the group, researchers should ensure that individual participants do not feel obligated to participate or fear consequences for declining to participate. The risk to confidentiality must also be discussed—although the individuals of the Havasupai remain unidentified, they have legitimate concerns about being stigmatized as a group.

There are two aspect of this problem 1. Individual autonomy: From the Michelle M. Mello et al article. Which focus on type of informed consent. It seem more specific purpose of using describe, more offensive but more burden for researchers. They recommended “Tiered consent” which combined specific consent and general permission. However, one of it’s disadvantage - sophisticated form. This problem may be amplified for people with cognitive or communication difficulty. It may raise doubt and burden for researcher to explain each items ( eg. What are other heath problems?) 2. Community perception: From this case study, it seem individual inform consents may not guarantee conflict with community belief. It need critical judgment whether that community’s belief need or no need to be changed. For example, in case of myth about HIV infection – definitely need correction for their well being. However, some historical or culture related issue are too sensitive to be manipulated ,or it should be address the community opinion before publish the result. I would like to share perspective as a person come from different culture. In some country, community and family in is very influence to personal expectation. People may feel comfort if they follow social norms or somewhat patronage. This may produce point of view differ from highly value identity and liberty society. In such case, I may choose to use general permission but more emphasize in community engage and understanding. In conclusion. I think it is good to aware autonomy in both level of individual and community. Thanks for nice blog!

Although there are challenges associated with obtaining informed consent for research involving blood samples, one should not forget that a subject has every right to be informed of what will be done or how their blood sample will be used for (future) research. It would be good to see a copy of the informed consent that they signed for this particular study. Hypothetically, Title 45 Part 46: Protection of Human Subjects was violated in this case, though there was no harm done to the involved human subjects. It is very clear that the tribe people gave blood samples and consented for research involving diabetes, but was taken advantage of their vulnerable situation and their consent was misused for research which they were not aware of. My thinking is what was IRB doing at that time? My impression is IRB, whose primary responsibility is protecting the safety, rights and welfare of research subjects, is equally accountable. Some of the points to reminisce when dealing with informed consent - relevant new information must be provided to the subject before and after the Study, when handling an ethnic or minority community, it is always best to have an advocate or a community leader to explain or translate to their people about the specific use of the specimens that were collected for research. Furthermore, other options must be explored like using a short form of the informed consent document stating that the elements of Informed Consent have been presented orally to the subject or subject’s legal representative and giving a copy of the signed and dated ICF. Blanket consent is another alternative, but no matter what, all investigators must be extensively educated on the informed consent process, GCP, CFR (US Code of Federal Regulations)and IRB.

The Havasupai Indians concerns regarding public perception and potential stigmatization of their tribe when their community is being scrutinized by researchers looking for a genetic basis for schizophrenia or the incidence of inbreeding are not unreasonable nor are they unexpected. Prior to the recent ethical issues raised by usage of banked specimens, informed consent was a necessary step in human research whenever there was the potential for physical harm (i.e. invasive procedure, receiving/not receiving a study drug). Now that samples are stored and housed in specimen-libraries for countless future studies, informed consent seeks to identify study subjects who will not be offended by how their samples are used. Preparing a consent form for a project that has not yet been identified is challenging. Although most study subjects have few objections on how their samples are used as long as their individual privacy is maintained, not all people feel the same way. However, we can predict which research areas are likely to raise the most debate. Therefore, I propose a modified tiered consent form for future research involving stored specimens. The consent form would specify a list of pre-determined research topics that are recognized by most reasonable people, as controversial or stigmatizing (human stem cell research, mental health disorders). Prior to specimen collection, subjects will be asked permission to use their samples in these pre-specified areas of future research. I do not favor a blanket or general consent for all genetics research involving stored specimens. In the Havasupai case against ASU, the researchers obtained written consent from all study subjects using a blanket consent form; the complaint raised by the Havasupai Indians against the ASU researchers was that they failed to inform the tribe the research questions their samples will be used for.