Sunday, July 18, 2010

NYT on Delay in publishing XMRV research

On July 14th, writing in the New York Times, David Tuller observed:

"Researchers at the National Institutes of Health and the Food and Drug Administration, citing a need to re-evaluate their data, have delayed publication of a new study believed to provide evidence of a link between chronic fatigue syndrome and a little-known retrovirus.

"The study, already peer-reviewed, was supposed to appear in the prestigious Proceedings of the National Academy of Sciences…

"Federal officials said publication was delayed because the findings contradicted those of the Centers for Disease Control and Prevention, which conducted its own study on chronic fatigue and the retrovirus, known as XMRV. The C.D.C. study, which found no connection, was initially also held up for reassessment because of the discrepancies, but was eventually published on July 1 in the journal Retrovirology."

There seems little doubt that the new research into XMRV by the NIH/FDA will eventually be published, but the delay in publication raises some serious issues.

That XMRV is itself a serious matter is unquestionable.  Theoretically, XMRV might be a contagious retrovirus that could render infected individuals non-productive and in need of prolonged medical and social care.  If a connection between XMRV and CFS were proven this could indicate that the infection is already established in the population and has been spreading undetected and unchecked for many years.  These possibilities make XMRV a potential major threat.  The threat must be evaluated and the information required for this will come from research.

What one might hope to see now is medical and scientific establishments acting to the highest standards of skill, professionalism and integrity for the protection of public health.

It is not necessarily irresponsible to publish research that contradicts other research when the written results have met the standards required by respected journals.  Researchers can describe and/or discuss contradictory findings.  It is accepted practice for researchers to propose further research based on their data and analysis.  In the case of contradictory XMRV investigations the obvious proposal would be investigations to discover why researchers got different results; so investigations into methods, patient-cohorts etc would be reasonable suggestions that might accompany or follow contradictory reports.

That this has already happened with XMRV should have been an indication to the CDC and NIH/FDA that while differing results might be frustrating and potentially embarrassing; this is an acceptable part of the learning-curve with new developments in science.  Mikovits et al published their findings of XMRV present in patients with CFS.  This was followed by McClure and others not finding XMRV present in their patients with CFS.  The debate and further research arising from these contradictory studies will probably further knowledge about XMRV and scientific methods.

Perhaps there are occasions where publication of contradictory research would not be in the public interest.  Then decisions about the 'greater good' would need to be made; though who should make those decisions remains undefined.  The World Medical Association Declaration of Helsinki, 2008, states:

"8.  Every medical research study involving human subjects must be preceded by careful assessment of predictable risks and burdens to the individuals and communities involved in the research in comparison with foreseeable benefits to them and to other individuals or communities affected by the condition under investigation."

This fundamental ethic applies to much of the current XMRV research in one very simple way.  The predictable risks and burdens are - you find the virus in participants or you don't.  There can be no question of these possible outcomes being overlooked - it's what the research is for.  If the CDC and NIH/FDA were not prepared for the possibility of either finding the virus or not - what on earth were they doing?

The Declaration of Helsinki further states:

"10.  …Authors have a duty to make publicly available the results of their research on human subjects and are accountable for the completeness and accuracy of their reports… Negative and inconclusive as well as positive results should be published or otherwise made publicly available…"

Therefore withholding publication of contradictory findings could be construed as unethical.  I cannot see that publishing the NIH/FDA research once it passed peer review could have been construed as unethical.  If an innocent and understandable mistake had occurred then explanations, retractions, or apologies could follow - this might be embarrassing but not unethical.

The NIH 'Mission' states (

"to exemplify and promote the highest level of scientific integrity, public accountability, and social responsibility in the conduct of science."  And adds that in realizing these goals they will provide leadership, "in directing programs for the collection, dissemination, and exchange of information in medicine and health…"

When such weighty institutions as the CDC, NIH and FDA put their scientists to work on a problem, the public might reasonably hope that answers will be found.  When concrete answers are not found due to limits of knowledge this might be frustrating but is an outcome that scientists and the public can generally accept. What should not happen is behavior that damages public trust in these institutions.  Publishing conflicting results might have prompted some debate - but I don't believe it would have damaged trust.

By withholding publication, albeit temporarily, the NIH/FDA have created an imbalance.  The CDC findings appear more reliable than those of the NIH/FDA.  They got published first, encountered less hold-ups and their data is out there for all to see.  The CDC seem to be more confident of their findings whilst the NIH/FDA appear nervous about their results.  When the NIH/FDA finally publish, their findings might be viewed with more, not less skepticism, because of the delay.  Quite simply, the CDC got there first - and that is often a good place to be.

It is not the difference in the findings of the CDC and NIH/FDA that I find particularly troubling, it is the difference in their response to these results.  Every researcher takes a risk when they publish - the risk that they missed something that could render their findings invalid.  Responsible researchers minimize the risk by being careful in the design and execution of their investigation, they study existing research in the field, invite criticism and submit to ethical, peer and editorial review.  Then they publish with the risks that inevitably remain.  Researchers that don't want to do this should probably consider finding a safer occupation less likely to cause disagreement and embarrassment.

Peter Kemp

July 2010

No comments: