When a two-decade-long search for an effective vaccine to prevent HIV infection has been a failure, the pressure to hype and provide spin to make results of a trial look successful increases. More so as only two trials have managed to reach Phase III, the final step in testing a vaccine. Aidsvax, the first Phase III vaccine trial done on more than 5,000 volunteers in Thailand, was found to be a failure in November 2003. The Phase II Merck trial in 2007 not merely failed; it increased the risk of HIV infection in those vaccinated. Unsurprisingly, the pressure to make the latest Phase III trial, conducted in Thailand on more than 16,000 volunteers, seem successful became overpowering. How else to explain the compulsions behind the positive portrayal of the Thai trial (RV144) results on September 24? It was announced that the trial using two different vaccines in a prime-boost regimen produced a modest preventive effect of 31 per cent in those who received the vaccine. What followed was euphoria among those working in the HIV vaccine field; this was the first time a vaccine was found to have the long-sought-after preventive effect.
The euphoria gave way to disappointment when the full results were announced in Paris on October 20 and published simultaneously in The New England Journal of Medicine. The paper contained other data (intention to treat, and per protocol) not mentioned in the initial announcement; and they failed to show a statistically significant protective effect. Why did the sponsors who were aware of these data in September not disclose them? The modified intention-to-treat analysis, which was not part of the original protocol design, was added six months before the data were analysed. This design helped remove seven volunteers who tested positive, thereby increasing the odds of a successful outcome. Unlike other HIV vaccine trials, this one had 76 per cent of individuals at low- and moderate-risk. The trials’ claim to success was based on moderate protection seen in those at low- and moderate-risk and not in those at high-risk of infection. This vital information was withheld initially. By cherry-picking the positive results, the National Institutes of Health (NIH), one of the sponsors of the trial, has laid itself open to the charge of breaching the ethical norms for reporting clinical trial results. Hyping results and imparting spin to the interpretation of trial data is clearly detrimental to science, and is not something expected from a nodal agency responsible for oversight.