Research 2.0 - For the genetic extrovert in all some of us

Identifying the ‘gene-which-senses-danger-ahead’ was not part of the 20+ traits my 23andMe genetic service report promised to include. I think lacking that gene is true for all of us who have consented to allow 23andMe to use our genetic information to conduct the 23andMe authorized scientific research. I prefer to claim I have the adventurer/explorer gene - it sounds more glamorous.

The New Open Paradigm

My first exposure to the concept of sharing personal medical information was a website called PatientsLikeMe. The purpose of this site is to give people diagnosed with life-changing diseases a forum to share medical information that potentially can improve the lives of others. The website creators plan to share this self-reported health information with doctors, pharmaceutical and medical device companies, and research organizations. The theory - as stated on the site - is that “openness is a good thing”. They continue with “when patients share real-world data, collaboration on a global scale becomes possible. New treatments become possible. Most importantly, change becomes possible”.

I was changed in my opinion of the benefits of "openness" as I read the very personal stories of people from around the world. One example was a mother with a young child from South Africa. Just when she thought life was going well, she was diagnosed with Parkinson’s disease. This mother publicly tracks treatments, medications, and supplements on the PatientsLikeMe website, and shares how effective they are. She also reports daily or weekly on symptoms like insomnia, anxiety, and even sexual dysfunction.




What is Research 2.0

I was already sold on the idea of sharing personal health information by the time I read that 23andMe consents all of its customers to participate in “a new kind of research that has the potential to produce valuable insights more quickly and less expensively than traditional methods". They call it Research 2.0, because "this new approach lets you initiate, advise and participate in research via the Internet".

Some of the major points I read in their research policies include:

1. 23andMe would not reveal my identity.
2. 23andMe would share the results of all research and show me how my contributions were making an impact.
3. The idea is to make possible large studies that would not be feasible using current methods.
4. The research will discover new genetic associations that could shed more light on my data, but without me expecting any financial benefit as a result of having my genetic data processed or shared with research partners, including commercial partners.
5. Nothing would be released to any outside company without my explicit consent.
6. 23andMe will continually update me about ongoing company sponsored research and let me know of other opportunities to get involved with research in genetics.
7. 23andMe intends to publish robust results of scientific studies that they conduct or that are conducted with their research partners.

Similiar Projects

Another high profile effort that is following this same philosophy is the Personal Genome Project (PGP), led by George M. Church, PhD, Professor of Genetics at Harvard Medical School. PGP is "building a framework for prototyping and evaluating personal genomics technology and practices at increasing scales". The major difference with 23andMe is that the PGP will do full genome sequencing (all of my DNA), as opposed to the 0.008 percent (or less than 1 in 10,000) of my DNA that 23andMe tests for. Of course, a $399 23andMe service is comparatively more affordable, whereas a full PGP genome scan costs in the tens of thousands of dollars, and is therefore subsidized for those who must complete a selection process.

Dr. Church did a great television interview describing his vision of Research 2.0 on the Charlie Rose program. The founders of 23andMe, Linda Avey and Ann Wojcicki, were also interviewed. As the cornerstone of their research, the Personal Genome Project is recruiting "individuals interested in obtaining and openly sharing their genome sequences, related health and physical information, and reporting their experiences as a participant of the project on an ongoing basis". I think I have the right gene for that. Sign me up!



Perspective from a medical geneticist



A New Research Model

For those of you anxious to dive into Grant’s DNA, please accept my sincere apologies for one more delay. I thought it important to spend some time (probably more than was needed) to explore some of the information and decisions prior to proceeding with testing. This will be the last hors d’oeuvres prior to the main course.

One of the intriguing aspects of the 23andMe service is the opportunity to participate in a variety of research endeavors—named 23andWe. This approach is called Research 2.0 by the company and could be fairly characterized as direct-to-consumer research. The idea is to collect not only DNA but information from 23andMe consumers using surveys and link the data. Currently there are 23 different surveys available on the site. Surveys are optional for participants.

Once again there is a marked contrast between this approach and the traditional medical research model I am familiar with. One of the most positive aspects relates to sharing research results. Many of my patients become upset when they learn that I am prohibited from returning research results directly to them because of federal research oversight regulations, and quite frankly I’m not too happy about it either. It doesn’t seem like the right thing to do. Given its funding, 23andWe is not subject to these restrictions and they state, “…we will share the results of all research and show you how your contributions are making an impact.”

This is an excellent way to engage and maintain involvement of their community. They also clearly outline the entire research process from proposal to publication. This pulls back the curtain on what is needed to conduct scientifically valid research—something that the general public usually doesn’t see. They also commit to keeping participants informed about the current status of the research project. Having enrolled many patients in a variety of research projects, I have certainly been frustrated by the apparent black hole that collects information and samples, yet returns nothing to my universe. This does not respect the sacrifice that our patients make to participate. Kudos to 23andMe for their commitment to information exchange.

In contrast, viewed through my pervasive paternalism there are some concerns as well. Many of these surround issues of privacy and information sharing that I discussed in the last post, so I will not reiterate those here. There are a couple of areas that do deserve additional comment.

Research Oversight

That there is a need for oversight of human subjects research is an unfortunate legacy of unsound, unethical and in some cases heinous acts performed in the name of medical research. Names like Mengele, Tuskegee syphilis study and Unit 731 have resulted in national and international standards for conduct of human subjects’ research. In the US, the Office of Human Research Protection (OHRP) provides leadership in the protection of the rights, welfare and wellbeing of all subjects of research conducted or funded by the Department of Health and Human Services. OHRP and related organizations have promulgated rules and regulations that establish Institutional Review Boards, Privacy Boards, Patient Safety and Adverse Event committees to ensure as best as possible that research is conducted according to the highest scientific and ethical standards. Since they are privately funded, 23andWe is not subject to regulatory oversight for their research. There are some important differences in procedures that are worth highlighting.

Consent

Subjects entering a research project must give consent to participate. The process of giving this consent usually requires the subject to read a consent document in the subject’s primary language (or with the aid of a certified translator) and at an appropriate readability level. The document outlines the nature of the study, the subject’s involvement, potential benefits and harms, disposition of information and biologic samples, rights and researcher contact information. A member of the research team is present to answer any questions. These consents are specific to a given project--that is if a subject enrolls in more than one project, a separate consent is required for each. In the case of 23andWe it appears that if one submits a sample and completes surveys, this information is subsequently available to any and all research activity approved by 23andWe. In navigating through the different surveys, no information was provided with the individual survey regarding how the information was to be used. Other than choosing which surveys to fill out there doesn’t appear to be any way for a 23andWe participant to participate in some research projects and not others.

Conflict of Interest

Regulated research requires explicit disclosure of funding as well as declaration of any potential conflict of interest. 23andWe indicates that all research must be reviewed by 23andMe’s “…internal and external review committees…for scientific and ethical merit, as well as potential interest to the 23andMe community.” In reviewing the various ongoing research projects on the website I was unable to find any specific information about the composition of these committees, nor any disclosures. They do acknowledge in the Privacy Statement that they (23andMe) may receive compensation from these research partners. The information on the Parkinson disease study notes that 23andMe received funding from the Michael J. Fox Foundation for Parkinson’s Research. No other funding disclosures were identified.

Inducement

Historically this issue was raised in the context of inducing individuals such as prisoners to engage in research with the promise of decreasing the length of their sentence. It has since expanded to include monetary compensation for subjects beyond covering expenses associated with the research and a modest honorarium. The ethical issue is to avoid tempting someone to participate in research that they would not otherwise choose. For most 23andWe participants this is not an issue, as they are actually paying to participate in that they have to purchase the test. However, in the case of the Parkinson’s disease study the cost of the 23andMe test is only $25 as opposed to $399 due to generous underwriting by Google co-founder Sergey Brin. I certainly can’t say if this would fall outside limits applying to regulated research, but it should be noted that those patients with Parkinson’s who participate will be participating in all 23andWe sponsored research, not just the Parkinson’s project as I could not find any information on the site limiting this participation.

The Science

This is a new research model, and it remains to be seen if the model will perform as envisioned. I look forward to seeing the methods and results of the research published and hope that this does increase the pace of discovery as hoped.

In her address to the Secretary’s Advisory Committee on Genetics, Health and Society, Katie Hood, the CEO of the Michael J. Fox Foundation for Parkinson’s Research (the largest private funder of Parkinson’s research in the world) in discussing the foundation’s partnership with 23andMe eloquently expressed the frustration of affected individuals with the slow pace of research, as well as the challenge of competing for limited research dollars. By using their resources to create research partnerships and offering these directly to affected members through services such as 23andMe, they hope to fulfill their mission of driving the best Parkinson’s research in order to discover improved therapies and a cure. I for one hope they succeed.

Read the next post - The Grand Opening - Looking Inside My Genetic Crystal Ball

Reading about Consents, Risks, and Privacy - Now the Fun Starts

I remember how excited I was when the test kit arrived in the mail. It felt so new millennium. Ordering the test online was in fact easier than buying an airline ticket - and compared to many fares, even less expensive! I was also lucky that the Utah Department of Health officials were not overly zealous like those from New York and California. I was still allowed the choice to investigate my biology on my own terms. But 23andMe made sure I read several pages of Consent, Risk, and Privacy policies before the order could be completed.

The Consent and Waiver section

“23andMe's service is not a test or kit designed to diagnose disease or medical conditions, and it is not intended to be medical advice.” This is probably the most important statement to be aware of. In other words, don’t make your own diagnosis, and don’t print your report and expect your doctor to review the entire thing with you. Another declaration includes “… accessing your genetic information through 23andMe does not translate into a personal prediction”. As you read further you learn that other disease factors are environmental and not genetic, that our understanding of genetically influenced disease may be incomplete, and that gene/disease associations are based on populations and not individuals.

The Risks section

This section presented statements about risks I might be exposed to by using the service.

“You may learn information about yourself that you do not anticipate.” Isn’t this true for any medical information we get as part of receiving healthcare services? Besides, I’ve already heard some interesting positive stories from what others have learned from their genetic test. For some reason I don’t have any fears of what I might learn, so no worries for me here.

“The laboratory process may result in errors.” Errors? In healthcare? With our advanced technology? That never happens. (Just joking). Again, not worried.

“You should not change your health behaviors on the basis of this information.” I’m male, so I’m genetically predisposed to difficulty with changing behavior. Add to that the fact that I’m single. I think I need to get a wife first to ‘encourage’ me change. For men with wives, don’t show them your test results. (To anticipate questions as to why I’m single - I do have the commitment gene, just not the lucky in love gene.)

“Genetic research is not comprehensive and future scientific research may change the interpretation of your DNA.” This simply means we do not have all the answers yet. Everybody should understand this. Actually, this just means job security (which today is worth its weight in gold).

“Genetic data you share with others could be used against your interests.” One option of the service is to share your results with other 23andMe customers. This is done by one person sending a share request to another, and the receiving person accepting or rejecting the offer. Obviously, I‘ve already decided to be all-in on the sharing business. Besides, I agree with an article that appeared in the London Times titled “Our genetic code should be no big secret ".

“23andMe Sponsored Research: We will analyze your genetic and other voluntarily contributed personal information as part of our scientific research with the purpose of advancing the field of genetics and human health.” I think many service customers will see this as a bonus. We want to volunteer, as it makes us feel we are part of something greater than ourselves.

And finally, “Collaborative Research will be de-indentified”. The collaborative research with this blog will be completely identified of course. We have to keep it interesting.

The Privacy section

This section informs the customer about the choices they have related to their private data.
• Participation in activities and services that involve personal information beyond initial account and Genetic Information is voluntary and permission-based.
• It is entirely within your discretion to provide information or answer survey questions.
• At your request we will delete your account and personal information linked to your account from our systems.

My first thought was I don’t need any more protection than this. I guess I will find out if that’s true or not. I have to admit though that I read all of this privacy stuff because I knew Dr. Williams would ask me if I did.

So after reviewing and contemplating the consequences, I opened the box, spit in the tube, and sent it off. A more detailed description of this step will be in the next blog. My DNA would not come back in the mail, but would be converted into electronic bits and travel over the Internet. What a futuristic voyage.




Perspective from a medical geneticist



Caveat Emptor!!

I have a confession to make. I don’t read all the end user agreements that come with my software and computers. For all I know representatives from a software company could show up at my door informing me that I agreed to pick grapes in Sonoma. Bill Gates may have a lien on my spleen!! My approach to the ubiquitous end user agreement is best summed up in the words of Blanche DuBois, “Whoever you are, I have always depended on the kindness of strangers.” I can only hope it turns out better for me than Blanche.

Seriously, the problem of the end user agreement is not a trivial one. Many view them as contracts of adhesion—essentially a take it or leave it agreement where the purchaser has no leverage with which to negotiate with the seller. So how does this relate to direct-to-consumer genetic tests? In order to purchase the service the user must agree to certain things. In the case of 23andMe the purchaser must agree to both consent and waiver and terms of service. I certainly don’t have the background to determine whether these documents meet the criteria to be called contracts of adhesion, but there are some points I think worth considering, particularly given the concern that the public has expressed about privacy of medical and genetic information.

General issues

I reviewed three documents from 23andMe; the privacy statement, the consent and waiver and the terms of service. These documents were respectively 8, 6 and 13 pages long, the last printing in 9 pt. type. I imported the first two into Word and ran the readability statistics package. The ease of reading was 31.6 and 34.4 (target being in the 60-70 range) and grade level was nearly 14. Medicare requires that its patient materials have a readability grade level of 5, and most health educators recommend nothing higher than 8th grade reading level for patient-directed material. This raises the question of how well the materials are understood by the reader (recognizing that in many if not most cases, the documents aren’t even read). As I sit here in my glass house heaving rocks the reader should know that the ease of readability of this post is 41.6 with a grade level of 13.4.

Potential contradictions

In the privacy statement, 23andMe states that, “We will not release your personal information to any outside company without your explicit consent.” Given my experience with HIPAA, medical records and research, I would interpret that to mean that I will be asked to give my consent for this information to be released each time. However, that explicit consent seems to reside in the terms of service which states in clause 9: “…you acknowledge and agree that 23andMe is free to preserve and disclose content to non-profit or commercial partner organizations conducting scientific research…” Finally in the research section of the consent and waiver it states, “We will analyze your genetic and other voluntarily contributed personal information as part of our scientific research with the purpose of advancing the field of genetics and human health.” As best as I can determine, by sending in your saliva you are giving explicit consent to contribute your DNA results to any and all research approved by 23andMe. If you add any information to your profile such as a health condition, age, weight, ethnicity, survey result etc. you have now given explicit consent for that to be added to the data available for release. This consent extends indefinitely unless you close your account at which time your information is removed from their database, however regarding any information already sent to outside collaborators “…we cannot guarantee that it will be destroyed upon request.” (Consent and waiver—Collaborative Research)

Saliva sample

In the privacy document under Genetic Information it states, “…DNA and saliva samples are destroyed after the laboratory completes its work…” However, in the terms of use in clause 17 it states, “Your saliva, once submitted to and analyzed by us, becomes our property.” (this is repeated in clause 18). The destruction of the sample is not referenced at all in the terms of service. As I understand it, the privacy statement has no legal standing—only the consent and waiver and terms of service.

Promises, promises

So what is really warrantied by 23andMe? From clause 3 of the terms of service (the omissions are not intended to disrupt the context): “…genetic information you receive…cannot be relied upon at this point for diagnostic purposes…Genetic discoveries…have not, for the most part been clinically validated…and the technology…has also not yet been validated for clinical utility.”; “…our testing service is not licensed by the relevant state and federal authorities for genetic testing conducted for health and disease-related purposes. Reliance on any information provided by 23andMe, 23andMe employees, others appearing on our website at the invitation of 23andMe, or other visitors to our website is solely at your own risk.” (Emphasis added) From clause 19 (Disclaimer of Warranties, which by the way is all capitalized which is known to reduce readability, so I eliminated them in this post): “…23andMe makes no warranty that…the service will be…unfailingly secure, or error-free…results …of the service will be accurate or reliable…any errors in the software will be corrected…23andMe specifically disclaims any liability with regard to any actions resulting from your participation in the service.”

Felons beware

23andMe in both its privacy statement and terms of use notes that it will disclose your information “…pursuant to judicial or other government subpoenas, warrants, or orders.” (insert your Bill Clinton joke here) This has been a concern for creators of DNA databases and in fairness there are no standards to guide anyone with regards to requests from law enforcement seeking to match a DNA specimen obtained at a crime scene to a DNA database.

What’s new with you?

We all know that genetic knowledge changes rapidly. Will you be able to take advantage of this new knowledge—given that you may have contributed to generation of this knowledge through the 23andMe research program? According to clause 13 of the terms of service the answer is: “You acknowledge that 23andMe may offer different or additional technologies to collect genetic data in the future and that your purchase of our Service today does not entitle you to any different or additional technologies for collection of your genetic data without fee, and you will have to pay additional fees in order to have your genetic data collected on any future or additional technologies.

Bottom line

Having now read these documents, I would certainly encourage anyone wanting to purchase the service to read them carefully and seek help for understanding what they say if necessary. I should also note that while I am “picking” on 23andMe in this post, it’s only because they were the service Grant purchased. All direct-to-consumer testing companies have similar end user agreements that deserve scrutiny. Now if you’ll excuse me I have to run home to read all my software agreements!!

Read the next post - Research 2.0 - For the genetic extrovert in all some of us

What is this all about?

Germany recently passed a new law significantly limiting the use of direct-to-consumer (DTC) genetic tests, which can only be carried out by a licensed doctor following the patient’s consent. In response, the UK–based PHG Foundation, an independent not-for-profit public health organization focusing on genome-based science and technologies to improve health, calls this law “a regressive and paternalistic approach that takes genetic exceptionalism to an extreme not seen in other jurisdictions”.

Because similar debates are still raging in the US, we decided to explore both sides of the issue. Grant Wood will openly share his results from a DTC genetic service. Dr. Marc Williams will give advice as a medical geneticist and Janet Williams as a genetic counselor. Both will guide Grant through any potential misinterpretations.


Influences on my decision

Hi. My name is Grant Wood. I work in the field of medical genetics and I consider myself very lucky in that I have a fascinating job. Genetics touches all of us, yet we are still at the point where it has this ring of mystique and futurism to it. In many ways we view genetics as future science; our individual and collective medical future. Genetics is still a relatively new field within healthcare, yet when I tell people about my work, they all want to share stories about a genetic-related condition that has affected them and their families.

My work involves building new computer programs that can help doctors and patients collect, track, understand, and use family health history and genetic/genomic information in patient care. Therefore I felt it made perfect sense that I should explore how technology – both gene chips (or DNA microarrays) and the Internet – could combine to give me access as never before to my own biology.

Then another serendipitous event happened. While participating with the 2008 Genetic Alliance conference, I spent a day with Linda Avey, co-founder of one of these new personal genomics companies called 23andMe, visiting and talking with congressional offices in Washington, DC about the Genetic Information Nondiscrimination Act (GINA) of 2008. I learned that 23andMe provides a service where subscribers can receive personalized genetic reports containing information related to 110 traits and diseases. Order the kit online, spit in the tube, send it in the mail. (More on this in the next post).

Linda Avey is in the center. I am on the far left. We are in the Speaker of the House's office in the Capitol building, Washington, D.C.

I started to think about what my questions and expectations would be if I decided to sign up for the service 23andMe provided. My list contained questions and thoughts like:

• Exactly what kind of information can 23andMe provide me about the 110 traits and diseases my report would cover?
• Would I learn something about myself that I didn’t already know?
• Would I discover information that I should immediately take to my doctor?
• Is genetics really a proven science, and what kind of research is still in progress?
• Would it be important for the information in my report to get added to my Intermountain electronic health record?
• Should I share this kind of information with my family members? What about other interested people?
• What kind of cool technology would 23andMe use to show me my genetic report?

The price for the test was high - $999 per test kit - so I put the option of testing on the backburner. A short time after our meeting however, 23andMe reduced the price of their service to $399. I immediately went online and ordered the kit. My journey was about to begin.




Perspective from a medical geneticist




My First Impressions

I'm Dr. Marc Williams. When the first Direct-to-Consumer (DTC) genome tests were made available to the public, my initial response was this is irresponsible and certainly not ready for use. I had concerns that we didn’t have much evidence for the significance of many of the results that were to be reported; we had little information about the accuracy of the testing itself and we didn’t know how to use the information to make recommendations to improve health. In addition people may find out things that they really didn’t want to know as part of the testing (such as finding they carry a mutation in one of the BRCA genes meaning increased risk for breast and ovarian cancer) without access to genetic counseling or that they may pursue expensive investigations based on a finding from testing (as has been seen with whole-body CT scans) that would stress an already overtaxed health care system. These concerns reflect those raised by the American College of Medical Genetics’ statement on DTC genetic testing.

As I reflected more on this I realized that my initial reaction was in many ways a stereotypical “doctor” response. How dare a patient take medical care into their own hands? In reality we are asking, nay encouraging, patients to take more and more responsibility for their own health and heath decisions. It is hypocritical to encourage patients to take responsibility on one hand and criticize them for doing so on the other. While DTC testing may not be a choice I would make as a patient, I must be willing to accept that others have a different perspective. Consider the example of alternative medicines such as herbal preparations. For a long time physicians scoffed at their usefulness and criticized patients who used them. Ultimately we harmed patients as they would not admit to using alternative medicines to us, rightly fearing criticism, leading to adverse reactions due to interactions with prescription drugs. In addition there is emerging evidence that at least some preparations may be beneficial for certain conditions.

If I am open to a patient telling me about the results of their DTC test it allows me to understand what they are concerned about and why. This may provide a teachable moment that will allow the patient to take action to make positive changes in their life. This approach, while not necessarily ‘scientific’ or ‘evidence-based’ reflects our Healing Connections at Intermountain Healthcare, in particular: I listen to you with sensitivity and respond to your needs; and, I treat you with respect and compassion.

I look forward to exploring with Grant his journey through his DTC genetic test results. I’m convinced that if I really listen to what Grant has to say, I may learn more from him, than he will learn medically from me. We hope this series will be entertaining and thought-provoking.

Read the next post - Reading about Consents, Risks, and Privacy - Now the Fun Starts