Statisticians review landmark HIV vaccine trial
Hopes ran high in 2009 when a New England Journal of Medicine article announced success in developing a vaccine against HIV, the virus that causes AIDS.
But a new Bayesian statistical analysis initiated at Duke demonstrates that the results were far from conclusive.
The world has been waiting for an HIV vaccine for almost 30 years, said Victor DeGruttola, a biostatistician at the Harvard School of Public Health who participated in the new analysis. "Its efficacy is an emotionally charged issue. The HIV vaccine study, called RV 144, had been viewed as the first evidence that suggested we were close."
New analysis of the RV144 data shows it is more likely that the vaccine actually has no effect compared to what was presented in the initial analysis. The new analysis also highlights the need to regularly use multiple statistical methods to review new medicines, said James Berger, a statistician at Duke University who spearheaded the study along with Peter Gilbert of the University of Washington and DeGruttola.
The results appear in the April 1 issue of the Journal of Infectious Diseases. The new analysis uses Bayesian statistics, which includes information from the original data and also data from previous HIV vaccine research.
The original RV144 study reported new HIV infections in 51 of the 8,197 volunteers given the vaccine versus 74 of the 8,198 participants given the placebo. These results suggested that the vaccine, a combination of two other failed vaccines, was 31.2 percent effective, with a p-value of .04. Many researchers and journalists interpreted the statistics to mean that there was only a four percent chance that the vaccine was not effective, and alternatively a 96 percent chance that it was 31-percent effective.
But its not that simple, DeGruttola said. He was dismayed with the interpretation and criticized it in the journal Science. He said the correct way to think about the numbers is to assume the vaccine does nothing. Assume it is water. Repeating the experiment 50 times, researchers would expect that one out of 50 times they'd find equal-to or greater-than 31.2 percent vaccine efficacy, he said, adding that these standard statistics ultimately say nothing direct about whether the vaccine works.
Berger said Bayesian analysis improves upon the standard statistical methods because it can make statements about the chance that the vaccine had some efficacy. The P-values, which were used in the original analysis, cannot. In the new analysis, the researchers explain that the p-value of 0.04 was misinterpreted and say that, using Bayesian statistics, there is no more than a 71 percent chance that the vaccine was effective at preventing HIV.
In other words, there is a 29 percent chance that the vaccine was not effective, not a 4 percent chance, he said.
Because of what is at stake in HIV vaccine research, the conversation related to RV144 has not always been as scientific as it could have been, Gilbert said. He has reviewed and devised HIV vaccine trials since 1996 and said the new analysis provides statisticians and non-statisticians with a golden opportunity to have rational, scientific, and careful discussions when determining false positive flukes versus real effects.
The new evidence doesnt give us any reason for great joy, or greater gloom, said De Gruttola, but the researchers agree that the Bayesian analysis provides a new framework to add increased rigor into future vaccine trials.
More information: "Statistical Interpretation of the RV144 HIV Vaccine Efficacy Trial in Thailand: A Case Study for Statistical Issues in Efficacy Trials," Peter B. Gilbert, et al. Journal of Infectious Disease, Vol. 203, Issue 7. doi:10.1093/infdis/jiq152
Provided by Duke University
- Adaptive trial designs could accelerate HIV vaccine development Apr 20, 2011 | not rated yet | 0
- Puzzling results from HIV vaccine trial Dec 03, 2007 | not rated yet | 0
- Future HIV vaccines -- if we build it, will they come? Jul 20, 2010 | not rated yet | 0
- A world first: Vaccine helps prevent HIV infection Sep 24, 2009 | not rated yet | 0
- Insight into HIV immunity may lead to vaccine May 06, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...
HIV & AIDS 4 hours ago | 5 / 5 (3) | 0 |
Detection of HIV antibodies is used to diagnose HIV infection and monitor trials of experimental HIV/AIDS vaccines. New, more sensitive detection systems being developed use microspheres to capture HIV antibodies ...
HIV & AIDS 20 hours ago | 5 / 5 (1) | 0
(HealthDay)—For HIV-infected individuals with recurrent Clostridium difficile infection, fecal microbiota therapy is feasible, according to a letter published in the May 21 issue of the Annals of Intern ...
HIV & AIDS May 22, 2013 | not rated yet | 0
Canadian health authorities lifted Wednesday what was effectively a ban on gay men giving blood, announcing new rules making men who have not had sex with men in the past five years eligible.
HIV & AIDS May 22, 2013 | not rated yet | 1
(HealthDay)—We've all seen them: the surfers who race to the beach when a hurricane hits, the guy who decides to ride out the storm in his overmatched boat, the tornado chasers who fearlessly steer their ...
1 hour ago | not rated yet | 0
(HealthDay)—New evidence-based guidelines provide guidance on medical and surgical methods for second-trimester abortion and management of associated complications, according to a practice bulletin published ...
45 minutes ago | not rated yet | 0
(HealthDay)—More than one in four of those eligible for new premium assistance tax credits under the Affordable Care Act (ACA) do not have a checking account and will not be able to receive premiums from ...
35 minutes ago | not rated yet | 0
(HealthDay)—Comorbid conditions often accompany alopecia areata, according to a study published online May 22 in JAMA Dermatology.
15 minutes ago | not rated yet | 0
(HealthDay)—As a world-class golfer, Stacy Lewis' accomplishments are remarkable. But it was a physical challenge in her childhood that defined her ascent to the top of her sport.
55 minutes ago | not rated yet | 0
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
1 hour ago | not rated yet | 0 |