Posts Tagged bioethics

Ethics and access to databases

This publication has attracted attention: Resolving individuals contributing trace amounts of DNA to highly complex mixtures using high-density SNP genotyping microarrays by Nils Homer and 9 co-authors, including David W Craig, PLoS Genet 2008( Aug 29);4(8): e1000167 [PubMed Record].

See, for example: NIH Limits Access to GWAS Databases Due to Privacy Concerns by Charles P Clayton, Alliance for Academic Internal Medicine, September 5, 2008. Excerpt:

The National Institutes of Health (NIH) announced new procedures for researchers to access previously public databases from genome-wide association studies (GWAS) in light of recently published research …

See also: NIH Tackles Privacy Concerns for GWAS, NIAID Funding News, September 17, 2008. Excerpts:

On August 25, 2008, NIH removed files of aggregate GWAS data from the public portion of its databases while keeping summary information public.

You will still be able to share and use these data. As an investigator, you must now apply for access and agree to protect confidentiality. This process matches the one NIH has required all along for individual-level data.

Read more about NIH’s new policy for accessing GWAS data at Modifications to Genome-Wide Association Studies (GWAS) Data Access.

Excerpts from NIH’s new policy:

The NIH developed a two-tiered access policy for GWAS data. The first level is the public posting (open access) of summary-level information and aggregate genotype data, including allele frequencies by case-control status, association tests odds ratios, and p values for each SNP in the scan. The second level is controlled access to individual-level data (genotypes and phenotypes). The controlled access data are available to investigators from scientific institutions who submit Data Access Request (DAR) packages that are reviewed and approved by the NIH Data Access Committees (DACs).

New statistical techniques for analyzing dense genomic information make it possible to infer the group assignment (i.e., case or control) of an individual DNA sample if one has access to high-density genomic data for that specific individual from another source and the allele frequencies for the case and control groups from publicly available aggregate datasets. …..

Two recent publications about research ethics in the genomics era:

Ethical and Practical Issues Associated with Aggregating Databases by David R Karp and 14 co-authors, PLoS Med 2008(Sep 23); 5(9): e190 [PubMed Record]. Excerpt:

Box 1. Recommendations

1. Determine whether initial consent and ethical approval will allow secondary research.
2. Ensure that there are appropriate data security mechanisms and review bodies to protect privacy interests in aggregated databases.
3. Informed consent should take into account the potential incorporation of data into aggregated databases.
4. Address special challenges of using data obtained from existing databases.
5. Pursue efforts directed at standardization of data.
6. Establish data sharing rules, including attribution of contributions.
7. Adopt “best practices” to avoid identifiability of the data.

And, Informed Consent in the Genomics Era by Deborah Mascalzoni, Andrew Hicks, Peter Pramstaller, Matthias Wjst, PLoS Med 2008(Sep 16); 5(9): e192 [PubMed Record]. Summary Points:

* Genetic cohort studies storing biological materials hold great promise for medical research, but also present new problems that are profoundly different from the classical clinical trial for which informed consent was developed.
* The classical risk/benefit analysis of physical harm doesn’t take into account new threats to the individual such as uninsurability, unemployability, genetic discrimination, or disruption of family relationships.
* Traditional informed consent may therefore no longer be appropriate when dealing with long-term studies using biological materials.
* Informed consent should be seen as an ongoing process between researcher and participant, and not just as a once-and-for-all decision.
* Research following the initial storage of samples needs to be likewise explained and may be announced using new communication methods.

The publications cited above are all in PLoS journals, and are OA.


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Open access genomes

Open access genomes! (but how is OA protected?), Dave Love, dave love’s blog, October 21, 2008. Excerpt:

We have come a long way in the last 15 years since Craig Venter and his company, Celera, refused to deposit their human genomic sequence in NCBI/GenBank and others who practice gene patenting deflated our collective tyres. I think that PGP understands the benefits of being OA, but I didn’t see anything on their website about a legal backbone to protect that access, such as a Creative Commons copyrights. I hope they will get some advice on this from librarians, lawyers, publishers, and others in the OA community!

For more about the PGP, see: More on the Personal Genome Project, Gavin Baker, Open Access News, October 20, 2008; Profile of the Personal Genome Project, Gavin Baker, Open Access News, August 06, 2008; The Personal Genome Project, George M Church, Mol Syst Biol 2005; 1: 2005.0030 [Epub 2005(Dec 13)].

Modified on October 21, 2008:

See also: From genetic privacy to open consent, Jeantine E Lunshof, Ruth Chadwick, Daniel B Vorhaus and George M Church, Nat Rev Genet 2008(May); 9(5): 406-11. Excerpts from the full text (not OA):

Box 3 | Key features of the Personal Genome Project’s open-consent policy

Open consent as part of the Personal Genome Project implies that research participants accept that:

* Their data could be included in an open-access public database.
* No guarantees are given regarding anonymity, privacy and confidentiality.
* Participation involves a certain risk of harm to themselves and their relatives.
* Participation does not benefit the participants in any tangible way.
* Compliance with monitoring of their well-being through quarterly questionnaires is required.
* Withdrawal from the study is possible at any time.
* Complete removal of data that have been available in the public domain may not be possible.

The moral goal of open consent is to obtain valid consent by effectuating veracity as a precondition for valid consent and effectuating voluntariness through strict eligibility criteria, as a precondition for substantial informed consent.

[End of Box 3]

Open consent. Open consent means that volunteers consent to unrestricted re-disclosure of data originating from a confidential relationship, namely their health records, and to unrestricted disclosure of information that emerges from any future research on their genotype–phenotype data set, the information content of which cannot be predicted. No promises of anonymity, privacy or confidentiality are made. The leading moral principle is veracity — telling the truth — which should precede autonomy. Although, in clinical medicine, veracity is the legal norm in many jurisdictions, physicians may try to justify the withholding of information by invoking the ‘therapeutic privilege’. In research, there is no such privilege, and when seeking informed consent from research subjects, distorted or incomplete information could undermine trust in researchers and in science.

Comment: Those contemplating OA to genetic data need to pay careful attention to the concept of “open consent“, and its emphasis on “telling the truth” and on “voluntariness”. It’s also noted in the full text that “in the PGP potential volunteers are strongly advised to discuss their participation with relatives“.

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Assessing medical ethics journals

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Free articles about human gene therapy trials

The January 1, 2008 issue (vol. 19, no. 1) of the journal Human Gene Therapy includes an editorial and five commentaries about adverse events and informed consent in human gene transfer trials. See: Debate over Safety of Gene Therapy Trials Focuses on Issue of Informed Consent, by Vicki Cohn, Press Release, Mary Ann Liebert, Inc., January 22, 2008. All of these articles are currently freely accessible:

1) Adverse Events in Gene Transfer Trials and an Agenda for the New Year, by James M. Wilson, the Editor-In-Chief (Human Gene Therapy. January 1, 2008, 19(1): 1-2. doi:10.1089/hum.2008.0104). Excerpts:

The fact is that gene therapy is, and will remain, a highly visible area of translational research with elevated scrutiny.

I encourage the professional gene therapy societies and various related foundations to work together in the new year to undertake a critical review of the conduct of our clinical trials. As you can see in the following commentaries, these are very complex issues and conflicts and biases are at times unavoidable. However, it behooves us to get ahead of this issue and put in place more effective ways to ensure that research subjects who courageously give of themselves can do so with a full and unbiased understanding of the risks and benefits of their participation.

2) Case of Leukaemia Associated with X-Linked Severe Combined Immunodeficiency Gene Therapy Trial in London, by Board of the European Society of Gene and Cell Therapy, Executive Committee of the Clinigene Network of Excellence, and Executive of the Consert Integrated Project (Human Gene Therapy. January 1, 2008, 19(1): 3-4. doi:10.1089/hum.2007.1221). Excerpt:

However, retroviral and lentiviral SIN vectors remain to be proven clinically to provide both efficacy and a lower, ideally negligible, risk of adverse effects, and long-term follow-up of respective clinical trial patients is a clear necessity.

3) If It’s Broken, Shouldn’t It Be Fixed? Informed Consent and Initial Clinical Trials of Gene Therapy, by Arthur L. Caplan (Human Gene Therapy. January 1, 2008, 19(1): 5-6. doi:10.1089/hum.2007.1010). Excerpt:

Nothing can make the death of a subject in a clinical trial anything other than a horrible tragedy. There are, however, steps that could and should be taken to help ensure that when a death or adverse event occurs there is less room for doubt about the adequacy of informed consent.

4) Informed Consent in Human Gene Transfer Clinical Trials, by Jeffrey Kahn (Human Gene Therapy. January 1, 2008, 19(1): 7-8. doi:10.1089/hum.2007.1228). Excerpt:

The challenge of improving informed consent deserves the same attention as the science and medicine of gene transfer, and only when we meet that challenge can we claim that the subjects in HGT research are truly protected.

5) Protections for Participants in Gene Therapy Trials: A Patient’s Perspective, by Suzanne R. Pattee (Human Gene Therapy. January 1, 2008, 19(1): 9-10. doi:10.1089/hum.2007.1214). Excerpt:

Respecting participants by including them in the process respects the gravity of the request made of them – to give selflessly of themselves to benefit others.

6) Human Gene Therapy, Consent, and the Realities of Clinical Research: Is It Time for a Research Subject Advocate?, by Tomas Jose Silber (Human Gene Therapy. January 1, 2008, 19(1): 11-14. doi:10.1089/hum.2007.1217). Excerpt:

A research subject advocate could enhance the protection of participants in gene transfer research by advising the research team about participant concerns, by verifying the appropriateness of the Data Safety Monitoring Plan, by monitoring adverse events, and, most importantly, by the direct interaction with concerned families, stressing availability throughout the study while maintaining a working relationship with and independence from researchers.

For another example of the “elevated scrutiny” that human gene therapy is receiving, see a commentary about the articles listed above, On gene therapy and informed consent, by Alan Milstein,, January 29, 2008. Excerpt:

January’s issue of Human Gene Therapy offers some intriguing commentary on the issue of informed consent in gene transfer trials.

I had represented the Gelsinger family after the death of their son in the experiment sponsored by Dr. Wilson and because I currently represent the family of Jolie Mohr, whose recent death renewed the debate over the informed consent process in this field of research.

See also: A comment from Paul Gelsinger on gene therapy and informed consent,, January 31, 2008. The final sentence:

Anyone considering joining a clinical trial needs to be aware that they are dealing with a system that is seriously flawed.

Clinical trials of human gene therapy are of great interest from a variety of perspectives, including bioethical ones. They also provide an example of an aspect of biomedical and health-related research that’s of interest to many people, in addition to those researchers who are active in the field. Human Gene Therapy, and its publishers, Mary Ann Liebert Inc., should be thanked for providing free access to the thought-provoking articles published in the January 1, 2008 issue.

However, it should also be noted that Mary Ann Liebert, Inc. is listed in the SHERPA/RoMEO database as a publisher that’s non-compliant with the access policies of a variety of funding agencies. There’s a “Liebert Open Option” for Human Gene Therapy [PDF, 74 KB]. Fee: $3,000.

So far, I’ve not been able to find any information about how Mary Ann Liebert, Inc. plans to respond to the recently-revised NIH Public Access Policy.

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