It was not always this way. Up until the late eighties, meetings of federally-funded AIDS research groups were closed affairs -- patient representatives were not even welcome as observers. Courageous and brash activists crashed the group meetings of the AACTG (then called simply the ACTG) and demanded not only to observe the meetings, but also to participate in decision-making. Fortunately, some investigators were wise enough to see that community input could only help to create more relevant and attractive trials. It is now mandated in grants and cooperative agreements that federally-funded AIDS research groups not only have functional CCGs, but that patient representatives and other advocates be full members of key committees and protocol teams. Frequently the CCG representative will be listed among the group's research paper authors, thus helping assure responsible oversight from a patient perspective.
In general, while a trial is ongoing, very few people have access to the data. Usually only the statistician(s) and DSMB get full summaries of key endpoint data. Even the principal investigator is unable to review the data in midstream. This is to ensure that no one jumps to conclusions about trends seen in a trial that are not yet statistically significant (like trying to figure out the average number of coin tosses after only three flips). Otherwise there is a risk that the investigators or others could consciously or subconsciously alter their behavior, and affect the trial's outcome. The investigators are said to be "blinded" to the endpoint data. The DSMB also tries to strike a balance between closely watching the trial, and not looking too frequently. The reason for this is actually pretty simple: every time anyone takes a look at the data, they increase the risk of prematurely declaring a winner, when in fact, not enough data (or "coin flips") have accumulated to really be certain. So when the sample size (the number of patients) is calculated for a trial, it is adjusted upward for each time the DSMB is expected to take a peek.
Because the DSMB is privy to such sensitive information, it is absolutely imperative they be as independent as possible. If premature "hints" about how a trial is going leak into the community it could cause people to make up their minds even though the data are not yet reliable. So an independent DSMB is an absolute necessity for credible research.
These independent review mechanisms also protect investigators who often do have financial and other ties to corporations keenly interested in the outcome of the research they conduct. For better or worse, these financial relationships are now so common as to seem unavoidable. Therefore it is crucial that investigators disclose these relationships whenever writing or speaking about their research or offering their expert opinion on matters that could affect the business of their patrons.
Marcia Resnick, the former editor of the New England Journal of Medicine, perhaps the most prestigious medical journal in the world, was among the first to speak out strongly about the risks of conflict of interest and requiring the routine disclosure of the investigators' financial ties along with publication. This was an important first step. After all, if you want to critically evaluate a research article, it's reasonable to want to know if the investigator had a financial stake in the outcome. Sadly, while everybody seems to agree with Dr. Resnick in principle, not all journals have taken such a firm stand on the right of the reader to consider possible conflicts-of-interest just as carefully as a study's methodology. Happily, this seems to be an area the National Institutes of Health is showing leadership in at this time, and some of the federally-funded research groups are already drafting, or putting in place, much stronger conflict of interest disclosure policies.
Back to the GMHC Treatment Issues February 2002 contents page.