If you were dying, you would probably want to try everything to prolong your life. And an American pressure group plans to ask the US Supreme Court to determine whether terminally ill patients have a constitutional right to access experimental drugs (see http://www.wlf.org/Litigating/casedetail.asp?detail=266).
Against this background, the BMJ asked in two recent articles (2007;335:478-9), should terminally ill patients have the right to take drugs that have only gone through phase I trials?
In the first article, Emil Freireich, from the University of Texas, notes that participating in phase I and II studies of “drugs that offer some promise helps [cancer patients] remain optimistic”. Unfortunately, most cancer patients cannot participate in phase II studies, through ineligibility or inability to meet the study requirements.
However, eligibility criteria fulfil regulatory and other study requirements, rather than being based on “reasonable evidence that patients who are ineligible would not benefit”. Freireich concludes that terminally ill patients should have the same privilege as the rest of us to decide their personal risk-benefit ratio.
Dean Gesme, an oncologist from Minnesota, counters that “the allure of promising new drugs continues to engender false hope”. Gesme argues that using drugs outside clinical studies after phase I still potentially exposes subjects to adverse events without a reasonable prospect that they will benefit.
Furthermore, new drugs could divert “time, resources, and attention” from symptom palliation and efforts to enhance quality of life for terminally ill patients. The move may also substitute “clinical enthusiasm and wishful thinking for evidence based medicine”.
“It’s easy to understand why patients want access to drugs even if we know very little about their safety or efficacy,” comments John Hall, Vice President and Global Head, Strategic Drug Development Unit at Quintiles.
“They’re clutching at straws and if you’re going to die anyway, many people feel it doesn’t matter if they suffer adverse events. It’s worth taking the risk for the small chance of benefit. From a medical perspective, doctors want to do all they can for their patients. So if the opportunity arises and the patient agrees, you can see why many physicians want to try an apparently promising experimental medicine.”
Overall, the impact on pharmaceutical companies would be neutral, Dr Hall believes. He points out that the number of patients is so small that a company would not gain much commercially if they were to charge for the compound.
The effect on development times and market perception could also cut both ways. Freireich notes that compassionate use programmes require doctors to systematically collect and submit data, which can accelerate approval. Gesme counters that use outside the trial programme could “subvert” recruitment into further studies and so delay approval.
“A drug might end up with an undeservedly poor reputation if a key opinion leader uses it unsuccessfully in half-a-dozen terminally ill patients,” Dr Hall remarks. “On the other hand, a drug could gain an early boost if it extends life in some patients by several months beyond that predicted.”
“It’s a difficult one,” Dr Hall concludes. “But at the end of the day, if patients could benefit, if doctors want to take the chance, and if the effect on pharma is neutral, why not give the experimental drug a try?”