The New York Times - October 19, 2009
Seth Berkley, Op-Ed Contributor

At a biotech conference last week, I asked a major industry scientist what he thought of the Thai trial announcement, and, although no additional data had been presented, he replied simply, "I don't believe it." Unfortunately, such pessimism may be hard to dispel and may ultimately thwart other efforts to develop an AIDS vaccine.

Even before this controversy erupted, it had been an effort to maintain sufficient support for AIDS vaccine research and development. In 2008, private and public spending on this vital mission declined by 10 percent from the year before. A few fanatical AIDS activists have even called for ending the American government's considerable support for AIDS vaccine research, and spending the money instead on AIDS treatment. Patient care is vital, of course, but it alone can only mitigate, not end, the pandemic.

This is why it is essential to clear things up.

The Thai study was the largest AIDS vaccine trial yet, following 16,402 volunteers for six years. It was a collaborative effort by, among others, the United States military, the National Institutes of Health and the Thai Health Ministry. (The organization I head, a nonprofit that conducts vaccine research and development but was not involved and has no commercial interest in the candidates tested.) The trial partners initially announced that the vaccine combination reduced the risk of infection by 31.2 percent in a statistically significant analysis.

A few days later, the trial collaborators began to brief researchers privately about additional data, including a second type of analysis that indicated the vaccine regimen had been slightly less effective than the first analysis suggested. This second analysis was not statistically significant, meaning that chance, rather than the protective effect of the vaccine candidate, might explain why fewer volunteers in the vaccinated group than in the placebo group were infected with H.I.V.

Some researchers questioned why both analyses weren't announced at the same time -- which certainly would have been preferable -- and suggested to reporters that the second analysis called the first one into doubt. The trial sponsors say they thought the complexities of the second analysis and all additional data were best explored in a peer-reviewed paper in a scientific journal and at a presentation at the AIDS Vaccine Conference in Paris this week. But with news outlets reporting that the trial results may be a fluke, there is a risk that they will be forever tainted, whatever the final analyses show. What's more, the stain of dubiousness may remain on all AIDS vaccine research and development.

That would be a shame. Although the candidate duo tested in the Thai trial did not prove to be a vaccine ready for the market, it may provide an unprecedented opportunity to learn how an AIDS vaccine can work. A comparison of blood samples from volunteers could indicate what specific immune responses the combination may have activated to provide protection. If so, this knowledge could help scientists improve upon the more promising candidates that have emerged since the trial candidates were designed a decade ago, and determine which ones are most likely to work.

This illustrates why the controversy over statistical significance is exaggerated. Whether you consider the first or second analysis, the observed effect of the Thai candidates was either just above or below the level of statistical significance. Statisticians will tell you it is possible to observe an effect and have reason to think it's real even if it's not statistically significant. And if you think it's real, you ought to examine it carefully.

Even if the Thai vaccine regimen turns out, on examination, to have had no real benefit, researchers will still learn from the trial, as they do from every study. Moreover, other noteworthy advances featured at the Paris conference this week will offer fresh hope for an AIDS vaccine. Years of investment and dogged science are providing leads for solving one of today's most pressing research challenges. Some 7,400 new H.I.V. infections occur daily throughout the world. Clearly we need better methods of preventing the spread of H.I.V., and no public health intervention is more powerful or cost-effective against infectious disease than a vaccine.

Seth Berkley is the president and chief executive of the International AIDS Vaccine Initiative.
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