Flawed cancer trials: a role for activist investors
The story Study Finds Flaws in Cancer Clinical Trials reports on a study designed to examine the adequacy of Phase 2 oncology clinical study design. Sophisticated investors won’t be surprised by the conclusions of the study–that Phase 2 oncology studies frequently fail to describe and account for historical clinical data used for efficacy comparison. In fact, sophisticated hedge fund investors frequently capitalize on this unfortunate fact, by shorting the stocks of selected small companies when their oncology candidates reach Phase 3.
Heck, even non-sophisticated investors can profit. Just short equal dollar amounts of the stock of every small company whose oncology drug reaches Phase 3 based on an historical efficacy comparison. If you sell when enthusiasm is high and hold the position long enough (and the commissions or interest rates you’re paying aren’t excessive), you’ll come out ahead, because these companies fail in Phase 3 more often than they succeed. And when they fail, their stocks usually fall through the floor.
But if profiting from the misery of cancer patients isn’t your cup of tea, perhaps you, the activist investor, could simply demand greater due diligence of the management teams responsible for these flaws?
February 11th, 2007 at 2:15 pm
A good benchmark assessment of the efficacy of drugs that come out of clinical trials, could be the Cell Culture Assay Test (Cell Function Analysis).
At present, clinical trials are highly empirical, they test drugs on general populations and then look for a clincial response and a treatment effect that is not likely to be a chance result. However, the side effect of this is inflexibility, some patients may unnecessarily be exposed to inferior experimental therapies.
A problem with the empirical approach is it yields information about how large populations are likely to respond to a treatment. Doctors don’t treat populations, they treat individual patients. Because of this, doctors give treatments knowing full well that only a certain percentage of patients will receive a benefit from any given medicine. The empirical approach doesn’t tell doctors how to personalize their care to individual patients.
The number of possible treatment options supported by completed randomized clinical trials becomes increasingly vague for guiding physicians. Even the National Cancer Institute’s official cancer information website states that no data support the superiority of more than 20 different regimens in the case of metastatic breast cancer, a disease in which probably more clinical trials have been done than any other type of cancer.
More clinical trials have not produced more clear-cut guidance, but more confusion in this situation. It is more difficult to carry out clinical trials in early stage breast cancer, because larger numbers of patients are needed, as well as longer follow-up periods. But it is likely that more trials would lead to the identification of more equivalent chemotherapy choices for the average patient in early stage breast cancer and in virtually all forms of cancer as well.
So, it would appear that published reports of clinical trials provide precious little in the way of “gold standard” guidance. Almost any combination therapy is acceptable in the treatment of cancer these days. Physicians are confronted on nearly a daily basis by decisions that have not been addressed by randomized clinical trial evaluation.
The needed change in the “war on cancer” will not be on the types of drugs being developed, but on the understanding of the drugs we have. The system is overloaded with drugs and underloaded with the wisdom and expertise for using them.
Patient tumors with the same histology do not necessarily respond identically to the same agent or dose schedule of multiple agents. Laboratory screening of samples from a patient’s tumor can help select the appropriate treatment to administer, avoiding ineffective drugs and sparing patients the side effects normally associated with these agents.
It can provide predictive information to help physicians choose between chemotherapy drugs, eliminate potentially ineffective drugs from treatment regimens and assist in the formulation of an optimal therapy choice for each patient. This can spare the patient from unnecessary toxicity associated with ineffective treatment and offers a better chance of tumor response resulting in progression-free survival.
Identifying patients with resistant neoplasms may not only spare them toxicity but may prolong their lives, by sparing them from the life shortening effects of ineffective chemotherapy.
Patients would certainly have a better chance of success had their cancer been chemo-sensitive rather than chemo-resistant, where it is more apparent that chemotherapy improves the survival of patients, and where identifying the most effective chemotherapy would be more likely to improve survival above that achieved with empiric chemotherapy.
With the absence of effective laboratory tests to guide physicians, many patients do not even get a second chance at treatment when their disease progresses. Spending six to eight weeks to diagnose treatment failure often consumes a substantial portion of a patient’s remaining survival, not to mention toxicities and mutagenic effects. In cases where there are several equivalent treatments available, patients can benefit from these assay-testing results as a supplement to other clinical data when deciding on a treatment option.
There may be some resistance to this approach from some oncologists, but no one has ever shown that harm could result from the use of these technologies.