March 17, 2006 — -- Shortly after receiving an injection of a new experimental drug on Monday, six men in a research unit in London fell violently ill and developed multiple organ failure.
Now, five days later, four of the men have regained consciousness, the BBC reports, while two are still under sedation in critical condition.
Their harrowing experience -- various reports indicate the men quickly swelled up, having undergone anaphylactic shock, or an extremely potent allergic reaction -- is casting light on the clinical trial process, a system that has undeniably made important and frequent discoveries in medicine, but also creates unavoidable risks for the people who volunteer to be test subjects.
It is not known why the drug the men were given, an antibody therapy known as TGN 1412, caused such serious side effects. The pharmaceutical company testing the product, TeGenero AG, insists that thorough animal studies were done before human testing began.
The trial was known as a phase one study, meaning that the drug was given to healthy people to help determine its safety. Rigorous animal testing is typically done beforehand, and the lowest dose possible is usually administered first. The next step, a phase two trial, includes giving the drug to people with the illness the drug is meant to treat to determine its effectiveness and side effects.
The final step before the drug is allowed to be prescribed is a phase three trial, where large amounts of people are given the drug. And after that, if the drug (or device) is proven effective and passes safety tests, it is usually approved for prescription use.
Unknown problems can arise at any step in this pipeline, researchers say, even when all the scientists involved try their very hardest to prevent any negative outcomes, said Dr. Ezekiel J. Emanuel, chair of the Department of Clinical Bioethics at the National Institutes of Health.
"When the risks are low, that doesn't mean they are zero," Emanuel said. "They might happen."
That's why test subjects are supposed to sign an informed consent form, which ideally defines that there are both known and unknown risks to being in any clinical trial, noted Dr. Greg Koski, a former director of the federal Office for Human Research Protections and an assistant professor at Massachusetts General Hospital and Harvard Medical School.
However, those risks can be easy to ignore, especially when enrollment includes a large sum of cash. Many trials offer economic incentives to volunteers, some of whom make a livable wage from being human guinea pigs in the name of science. This trend was documented by Bob Helms, a self-described human guinea pig who wrote the book "Guinea Pig Zero." Read his story here.
"I don't know if anyone has a good count, but there's little reason not to believe that there will be people who will do this purely for financial reasons," Koski said. "Basically, they are willing to put their own safety at risk in order to make the money. Because of that vulnerability, extreme care has to be taken not to induce people to things that are unduly risky."
While there are always risks to these human guinea pigs, reactions as serious as what happened in London remain unusual -- which is why the trial was immediately halted and investigators have been brought in to examine what could have led to such horrible circumstances.
The start of a phase one trial is not the most risky part of the pipeline -- it's usually the phase three portion, when a large amount of people receive a drug, increasing the chance that underlying side effects could occur. But phase one trials are unique in that they are the first time a human receives a drug.
"Even though you may have done extensive testing on animals, animals are simply not humans," Koski said. "When you are the very first human being to be injected with a new compound, you just don't know what's going to happen."