Saturday, June 29, 2013

Correcting the Medical Literature: It's Not Just About the Future

A couple of important papers have recently appeared in the BMJ:

These have to do with an initiative called RIAT, for "restoring invisible and abandoned trials." A flaw in past work addressing commercial influence on medical research, leading to failure to publish or to distort important scientific findings, has been the focus on how to change things for the future so that these abuses no longer occur. That ignores the fact that the existing scientific literature, which continues to be the basis upon which decisions are made about treatment as well as about future research priorities, remains tainted so long as it's uncorrected for past abuses.

The authors, who have been involved in a variety of actions involving the pharmaceutical industry that gained them access to unpublished studies, provide a table of more than 100 studies known to them, which were either never published or were published only in distorted form. The authors refer to a type of document most physicians have never seen--a clinical study report. This document is the internal report of a research trial compiled for use by a pharmaceutical company, and adheres to fairly strict standards for inclusion and organization. They typically run hundrerds or even thousands of pages (for a study that when published in a journal would ordinarily occupy 10-15 pages). It is the clinical study report that the company typically submits to the FDA to support a request for new drug approval, though the FDA treats these as proprietary and refuses to release them publicly. The European Medicines Agency has inaugurated new public access policies that now make materials available that previously were kept secret.

The authors propose a detailed and well-thought-out plan for first allowing the original investigators of all these trials to proceed to publish them in a responsible and accurate way. If the original investigators refuse or decline, the clinical studies reports would next be made available for new authors to review and report on, following established protocols to assure quality and accuracy (along the lines of the current Cochrane Collaboration systematic reviews). The goal is to fill as quickly as possible as many of the known gaps in the scientific literature as possible.

The authors' main point seems to be that so long as these clinical studies reports exist (and there are no doubt hundreds more beyond what these authors personally have copies of), there exists a mechanism to correct the scientific literature and to fill in these gaps. Not to take advantage of that fact would be irresponsible.

The accompanying editorial by Drs Loder, Godlee, and others states the issue succinctly:

"Nothing better underscores the urgency and importance of the RIAT proposal than the list of abandoned trials that accompanies it. Read it and weep: on the list are clinical trials for drugs used by millions of people, including zanamivir, atorvastatin, gabapentin, and paroxetine. The number and variety of drugs on the list show clearly that incomplete reporting of clinical trial results is not an isolated occurrence, confined to a few drugs. Rather, it is an entrenched and widespread problem. Secrecy and selective reporting were an integral part of the system. Reforms such as trial registration and mandatory results reporting will improve things in the future but can do nothing about the flawed evidence of the past....

"The results of clinical trials are a public, not a private, good. The public interest requires that we have a complete view of previously conducted trials and a mechanism to correct the record for inaccurately or unreported trials. If we do not act on this opportunity to refurbish and restore abandoned trials, the medical research community will be failing its moral pact with research participants, patients, and the public. It is time to move from whether to how, and from words to action."

1 comment:

VEGF antibody said...

Interesting article on medicine! very informative.