I want to share some of the issues that I have with the FDA and the processes it uses for drug and treatment approval.
The FDA demands that a drug, to show efficacy, be tested first in animal models that often are not relevant to humans. Then when the drugs are approved for human trials, they can only be tested in terminally ill patients. Many agents that would be effective in earlier stages of the disease are therefore thrown out without ever knowing if they could have been effective.
The end point sought in most drug clinical trials, even in end stage patients, continues only to be survival. Very few, if any, surrogate markers are allowed to be used to gauge the biologic efficacy of the drugs. Possible surrogates or bio-markers which I believe should be considered in the trials can include proteins being produced by the abnormal genes, as well as processes and pathways that distinguish cancer cells from normal cells such as formation of new blood vessels or angiogenesis.
If a drug does not produce the desired clinical end point, survival, it is likely to be abandoned completely. This means that we never get to evaluate the drug’s potential biologic activity which may be harnessed for more effective use in combination with other agents.
I do acknowledge that the FDA has don an excellent job in protecting patients from snake oil and dangerous drugs. However, without the reevaluation of their standards we are also loosing may potentially good treatments and drugs.
Joel T Nowak MA, MSW
While I have no intent to be irritating, I need to advise you that there are some inaccuracies in your above blog.
Firstly, the FDA has never insisted that new cancer agents “can only be tested in end-stage patients.” That is a decision commonly taken by the drug company applicants because they think it is the quickest way to market (which is far from necessarily being the case). The last time I was involved in development of a potential new prostate cancer drug (not so long ago), we actually tried a trial of this drug very early in the process of disease progression (rising PSA after radical surgery or radiation therapy for localized disease) because we truly thought it would work in that scenario. Unfortunately it didn’t.
Secondly, the FDA has made enormous efforts, in combination with others, to validate surrogate markers for prostate cancer and many other forms of cancer. The problem is that to date, in the vast majority of cancers, these surrogate markers have failed to actually correlate to biologic efficacy. PSA is the obvious and simple example. Driving down PSA levels has never been shown to have any statistically meaningful impact on survival or time to any other documentable form of disease progression.