 So our next speaker is Valerie Gutman-Cotts, who is the director of law and ethics at the McLean Center for Clinical Medical Ethics and a visiting fellow at the Paul University's College of Law. Her work focuses on how medical and technological advances impact the law and how policy can be better equipped to address these changes. Professor Cotts serves as the chair of the American Bar Association's special committee on bioethics and the law, as well as the co-chair of the Law Affinity Group for the American Society for Bioethics and Humanities. Today she'll be giving a talk titled, Inform Consent and Direct to Consumer Genetic Testing. Please join me in welcoming Dr. Cotts. So I'm not talking about families or children. I am talking about genetics, and so I think this actually flows quite nicely from Dr. Ross's talk. So thank you. And thank you, Mark, for having me. So in past years, I've addressed issues of informed consent up here. I've talked about delegation of informed consent in the doctor-patient relationship. I've talked about a proposal to eliminate legal liability for informed consent, again, in the treatment context. Today I'm talking about informed consent in the research context, and specifically as it relates to direct to consumer genetic testing. It's notable that the subject is, what is notable about the subject is the absence, I think, in a lot of ways of any sort of relationship. So a doctor-patient relationship, an investigator, participant relationship, and so it raises, I think, pretty novel questions of informed consent. And sorry, Angela, I am using slides. But a little history. No disclosures. So in 2018, 23andMe announced a $300 million partnership with GlaxoSmithKline to allow the drug behemoth to develop drugs based on de-identified DNA and other information collected from its direct to consumer or DTC genetic testing companies' customers. And just a couple weeks ago, 23andMe announced a partnership with a brand new company called TrialSpark, which allegedly partners with doctors to create FDA-compliant trial sites in order to unlock an opportunity for sponsors to conduct trials that are patient-centric, faster and uniquely data-driven. These efforts are indicative of the evolving research model utilizing biospecimens and personal information that's collected by direct to consumer genetic testing companies. And in fact, this type of research could produce a number of transformations in the model for clinical research, leading to a number of potential advantages like diminished recruitment and enrollment problems as the patient pools become larger and more diverse, and advantages of reproducibility as doubts about the validity of the results and uncertainty about conclusions could be reduced as investigators could more easily reproduce each other's research if they have access to these databases. But underlying all of these claims are arguments that research arising from direct to consumer genetic testing is collaborative, patient-driven and democratizing. In fact, the social networking-based companies advocate the democratization of research and the collaborative nature of patient-driven research, heralding a novel and primary role for participants of human subjects research. But ultimately, as this 2001 article quote makes clear, the business models of these direct to consumer genetic testing companies are dependent not on the sale of these recreational genetic tests that tell you about whether you can curl your tongue or whether your ears are attached or not, but from gathering the genetic and personal data that can be used for in-house research or licensed and sold to third-party institutions, academic researchers, or drug companies. So this chart is from a 2011 Nature article, or 2012, that demonstrates the increase in the number of samples in certain companies' biobanks. The blue line represents 23 MEs biobank from 2006 through 2012. And by 2016, it could be, quote, safely assumed that 23 ME had a collection of hundreds of thousands of biological and DNA samples. So these numbers raised important questions, including how collaborative these efforts are actually are. If a direct to consumer genetic testing company and their entire profit is dependent on the research that arises from the collection of biospecimens and data from the consumers that actually purchased their kits. And I would argue it's not very collaborative, right? Under 23 ME's research revolution model, which was the model that was introduced by them in 2011, collaboration consisted of a single vote for the disease on which research would presumably be focused. And this vote, of course, was purchased with cash, right, paying for the recreational test itself and release of information, including genetic data, physical traits, health history, and behavior. So under this research revolution model, it could not, I argue, be claimed that participants were actually directing research. Consumers did not have a say in the contours of the research or selection of the investigators who would conduct the studies. The power to make all of these decisions, and more, remained and still remains in the hands of 23 ME and its partners. So the fact that research participants may never know how their information is being used directly conflicts with the notion that patients or consumers or participants or however we want to define these folks are driving research. Today, consumers consent to participate in research utilizing their biospecimens and phenotypic data without the company's disclosure of its research agenda. So while 23 ME's research model continues to herald a primary and novel role for participants of human subjects research in treating them to become part of something bigger, claims of collaboration or democratization are misleading. Research arising from the collection of genetic samples and personal and genealogical information raise important questions of voluntariness and informed consent since this type of research differs in crucial ways from the traditional model of research. As with research arising from biobanking generally, participants genetic and phenotypic data may be used for any number of studies, may focus on any number of genetic traits and illnesses, and may be conducted by any number of investigators. These facts challenge historic expectations of how research protocols are defined and what it means to participate in research. And in fact, an individual sharing of his or her genetic information for recreational purposes may not actually demonstrate a desire or intent to even participate in research in the first place. Many scholars and policymakers worry that this research may occur without consumers' real knowledge or understanding. So this is a screenshot from 2012 from the 23 Enmys informed consent website when I first wrote about research arising from direct-to-consumer genetic testing. Today, this is a screenshot from 2019, 23 Enmys customers are the option of filling out a biobanking consent document which allows the company to store an individual's biospecimen for undefined future research purposes. Receiving consent to biobank and individual's biospecimens allows the company and its contractors to access and analyze the individual stored sample using the same or more advanced technologies, that's a quote, as permitted by its terms of service and privacy policy, another form on the website. Even if a 23 Enmys customer does not then consent to biobanking here, according to this form here, his samples may still be preserved according to the general privacy policy under 23 Enmys, subject to the laboratory's legal and regulatory requirements. Thus, although the mechanism to consent to research has evolved since I first started looking at this issue, many participants may still not truly understand that they are, as some have argued, quote, paying for the privilege of 23 Enmys working with a for-profit company in a for-profit research project. Well today's consent form is considerably longer, you can keep scrolling down. It still suffers from insufficiencies. One study of direct-to-consumer genetic testing companies approached to inform consent and research concluded that it, quote, clear, it is clear that the consent procedure currently used is ethically inadequate. Further, there is no process, and customers opt for testing and consent to research without input from a clinician or genetics counselor. And these forms and this process, this lack of process, gives individuals no power to negotiate or make choices about their participation. So like with click-through agreements that we encounter with so many apps, Uber, Facebook, Twitter, et cetera, consumers, or in this case, are the research subjects, aren't really able to exercise authority and can only agree on sort of a take it or leave it basis. And some have argued that this is, in other words, a contract of adhesion. So despite these concerns, however, 80% of 23andMe's 10 million customers have consented to share their genetic and phenotypic information for research purposes. 23andMe sells its model to third party scientists that they're seeking to partner with as, quote, the largest recontactable research database of genotypic and phenotypic information in the world. And while the company promises that customers can opt out of research by closing their 23andMe account, quote, any research involving your data that has already been performed or published prior to our receipt of your request will not be reversed, undone, or withdrawn. So this raises, from my perspective, a question about what role the law has to play in ensuring that informed consent for enrolling consumers in research arising from direct to consumer genetic testing is in fact sufficient. The legal and regulatory system that currently exists to protect human subjects in research may be inadequate to address participants in this type of genetic research. So the common rule, which is the set of regulations that govern a majority of research conducted in the United States, has specific requirements for informed consent and IRB oversight for all research involving human participants. In 2012, I concluded that whether the common rule at the time, which was the original version of the common rule, whether it applied to research arising from DTC genetic testing companies remained unsettled. The common rule, the 1991 common rule, failed to clarify whether research arising from direct to consumer genetic testing from the collection of biospecimens and data constituted human subjects research and therefore were actually subject to IRB oversight informed consent requirements as required by the rule. So this lack of clarity was referred to by editors of PLS Genetics as a quote unfortunate loophole that therefore validated the company's consent or lack thereof consent procedures. In 2017, the first ever revisions to the common rule were finalized. There were delays in implementation which affected its rollout. But despite many proposals during the process of revising the common rule in order to expand the definition of human subjects research to include all biospecimens, regardless of identifiability, regardless of those efforts, the final rule did not include such an expansion. Policy makers were concerned that doing so, that expanding the definition would unnecessarily hinder research by overwhelming researchers with excessive administrative duties. Therefore, the revised common rule maintains the previous understanding that secondary research utilizing deidentifiable specimens does not qualify as human subjects research. And therefore IRB oversight and informed consent in those cases is not necessary. Further, to acknowledge the modern practice of collecting biospecimens for secondary unrelated research, either research or clinical purposes that are then used for future research protocols, the revised common rule created a new provision explicitly outlining the process by which an institution can procure broad consent rather than study specific consent for secondary research unidentifiable biospecimens. The revised common rule also has a number of other elements. It aims to address the modern research climate by requiring certain disclosures as part of the informed consent process. So for example, the research involves collection of identifiable, not deidentifiable, but actually identifiable biospecimens. The consent form must include either a statement indicating that the identifying aspects of that data may be removed and that the information may be used for future research studies or distributed by another investigator or a statement that the participants data will not be shared. Further disclosures concerning whether the biospecimens may be used for future commercial purposes and whether the research may involve whole genome sequencing may also be required in the informed consent process. Also relevant to direct to consumer genetic, oversight of direct to consumer genetic testing companies, the rule does not require return of results, of research results to participants, even though presumably that's why consumers are doing these tests in the first place. So does the revised common rule appropriately protect individuals who use direct to consumer genetic testing services and whose information and biospecimens are collected and used in future research protocols? I would argue probably not. Despite efforts to update the federal regulations to address technological innovations in human subjects research, the revised common rule may still not adequately protect those individuals. There's little in the revised common rule to direct or guide direct to consumer genetic testing companies to ensure a more robust informed consent process for the use of customers, biospecimens, and data. Rather, the rule enables these companies to more easily perform secondary research utilizing customers' information and biospecimens while doing little to regulate or guide these companies in conducting the ethical conduct of research or protecting patient autonomy. In fact, by adding a broad consent pathway to the already existing study-specific consent protocol that was required under the original common rule, it gives direct to consumer genetic testing companies and their partners more opportunities to use identifiable and non-identifiable or de-identified biospecimens or collected data. So in many ways, the final rule permits companies to continue to market themselves as proponents of democratizing research, despite doing little to shift research from a single direction endeavor to a collaborative process shared by participants and researchers. The apparent demedicalization of health information and analysis into a form of social entertainment has raised serious questions about informed consent. The lack of clarity regarding use of one's genetic information implicates individual agency. Not only does the status quo fail to improve the status of individual customers who find themselves to be participants in research utilizing their biospecimens and data, it also undermines public trust. Thank you. And for more. Thank you. Giving them their genetic information. And then if people are then going to do research on this information, it's going to exacerbate the problem where we have more information about who is more privileged, and therefore we are creating improvements for people who are privileged and who has the information we have. Is there anything in this sort of research to protect that? Is there talk about that in people worry? There's a general worry about these types of biobanks, not necessarily 23 of me specifically, but across the board about that type of bias. There's a lot of evidence that precision medicine initiatives are and the biobanks upon which a lot of the research is based is very much skewed to a very specific population that is not representative of the diversity and inclusive of the diversity that our population would require. And so there's absolutely that issue. The question about payments is very interesting. I had a very nice conversation last night with Emily Landon about the cost of the kits, of 23 of me's kits specifically, because it's almost marketed at this perfect amount, that it used to be very, very high. Now for the holidays, you can get it for $50 or something like that. It's whatever, a half off. So it's enough that you think you're getting something. You're paying for the privilege of getting these test results back, but it's not enough that you're not going to do it and then also consent to research. So there is this marketing effort to identify a very specific element to the population. I think that would then also the 80% obviously click through and say, yeah, I can send for research. Thanks, John Landon. Just a clarifying legal question. My understanding was the common rule only applies to the federal agencies that have signed on to the common rule and only for research that they fund. So does it even apply to private companies like 23 and me? Yeah, so the common rule itself applies to all federally funded research in this country. It also applies to any institutions that have signed on to an FWA, a federal wide assurance. And then the common rule itself is very, very similar to the FDA regulations. So if you are trying to create any sort of pharmaceutical, you are going to have to abide by these rules. They are actually in the business now of developing pharmaceuticals, for example. They are partnering again with GSK and other partners. And so a lot of their partnerships have led themselves because of the central IRB requirements, too, now under the new revised common rule that they will be subject to common rule requirements. At the mic. Dirk van Leeuwen, Dartmouth College. I'm going to be the devil's advocate. We are, in all these genetic research, constantly, let me put the perspective, terrorizing the life of any researcher by all the regulations that we create. Society at large wants to menacingly benefit from all the advantages, unless. So should we not start completely at the other end? Whoever wants to collect can collect. And the provisions that disclosure that do harm are prevented. That should be the starting point, instead of this crazy regulation line that costs zillions of dollars that we could so much better spend than we are spending it now. It's very simplistic, of course. I think that the history of human subjects research in this country and internationally sort of belies that argument. I think it contradicts that argument in favor of sort of a free market for research and allow anybody to sort of do whatever they want, and hopefully nobody's harmed. The way that our regulation, again, I'm not arguing that in some ways our regulation might not also be overreaching, but it is overreaching in reaction to this history of atrocities that have occurred and scandals that have occurred in this country and elsewhere due to failure to obtain voluntary first person informed consent to research. So I am hesitant to say we should just eliminate all oversight and then piecemeal it together and figure out what actually works and not. I would propose protections, but the complexity. Now, every time again asking consent, it can't be one way that patients only want to benefit and don't want to have any risk and don't want to contribute. I think it is totally a sick concept by now. I make it a little bit black and white. Appreciate your comment. Thank you very much.