A few weeks ago much propagated microbicide trials designed to test the efficacy of a microbicide aimed at reducing or preventing HIV transmission during sexual intercourse ended in failure. It turned out that the microbicide actually increased the risk of HIV infection. All sorts of ethical questions arose, of course, including whether an infection acquired during the course of the trial should count as a trial related injury that ought to be subject to compensation.
Well, much better resourced preventive HIV vaccine trials also crashed in a spectacular way today. Again, it turned out that the trials left those who were injected with the vaccine candidate more susceptible to HIV infection than those who were in the placebo arm. In all fairness to those who undertook this trial, the plug was pulled quickly when these results came to light. Equally, how would one ever find out whether a vaccine candidate works other than by means of undertaking such trials. So, the problem with both the microbicide trials, and the preventive vaccine trials isn't that they took place at all. The problem is to do with the question of what is owed to those who became already infected during the course of the prevention trial, and to those who are now at greater risk of catching an infection. There were also clear failings in the informed consent process.
I think these quotes from two of the participants are revealing in important ways. I found them in an article in the Washington Post:
"It's quite shocking," said Nelly Nonoise, 26, who had received three injections of the vaccine in her left shoulder. She added, "I probably wouldn't have joined the study knowing there's a risk." Another participant, Nonhlanhla Nqakala, 22, said she thought the text message urging her to visit the vaccine test site meant she had tested positive for HIV. Her brother and a close friend had the disease and died, she said. Nqakala said she was relieved when a doctor explained that she was not infected, but the news of a possible problem with the vaccine -- she had received three doses, not placebos -- left her distressed. "I thought the trial would help us find a cure for HIV," she said."Now, here is a problem obviously! Two people are being interviewed by the journalist, and both indicate that they didn't understand properly the nature of the trial. This does not reflect well on the investigators' professed best practice standards in their informed consent process. It seems obvious that they happily accepted participants into their trial who did not actually comprehend the nature of the trial.
Again, the question is what is owed to the trial participants by the trial sponsors and / or the investigators. Surely if you accept people into your trial that end up being worse off when the trial is stopped, you have some responsibility for these folks, particularly so when obviously you took participants into the trial that didn't understand what was going on in the first place.
And yes, this smug ethicist can claim without embarrassment that 'I told you so' prior to the start of the trial. I argued that trial participants' competence and level of information / comprehension needed to be tested in order to rule out that people would end up in the trial that do not understand its nature. This was rejected at the time with arguments such as 'we would never be able to recruit enough participants then'. So the public health and research imperative was prioritised over individual participants' well being.
Lessons to be learned: Well, to be frank, the warnings were there prior to the trial and they were ignored. That one should not do this isn't exactly a new lesson, so, if anything we should probably consider erring on the side of caution on the odd occasion in future.
The Washington Post cites the Principal Investigator with these remarks:
"This is my worst nightmare," said Glenda Gray, the lead South Africa investigator for the vaccine study. "I haven't slept for days. I have a headache. I'm ready to resign from trials for the rest of my life."
Of course, while I have no doubt about Glenda Gray's integrity as a researcher, and while I have no doubt that her current qualms are genuine, much of this could have been avoided if sensible procedures in terms of the informed consent process had been put in place, including knowledge and comprehension evaluation of the prospective participants. The failure to do so puts the moral responsibility for this trial's failure squarely on the shoulders of the trial sponsors and investigators. It's not about resigning from clinical trials, it's about avoiding ethical short cuts (for instance in the informed consent process).