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Published online 1 April 2008 |
Nature
| doi:10.1038/452510a
Corrected online: 30 April 2008
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Drug markers questioned
A recent spate of worrying clinical-trial data has researchers questioning drugs approved on the basis of how they affect biomarkers rather than clinical endpoints. Heidi Ledford looks at surrogate markers.
Forty years ago, a debate raged among cardiologists over the nature of the link between high blood pressure and heart disease. Some believed high blood pressure was a causal factor in producing heart attacks and strokes.
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FDA’s primary mission for over 90 years has been to promote and protect the public health, under the authority of the Federal Food, Drug, and Cosmetic (FD&C) Act and the Public Health Service Act. The FD&C Act requires that new drugs be shown to be safe and effective before being marketed in this country. In the particular case discussed here, if a drug is to lower blood pressure then demonstrating its ability to do so should be sufficient for market approval. However, the question remains – can it do this safely!? If in the given context lowering blood pressure is considered unsafe, this should be defined first of all by the medical field in general, by practicing physicians, and should be fully considered by the FDA during the approval process. It does seem that this comprehensive approach has not yet been developed but I do not think that the FDA alone can be blamed for this. It is expected that evidence of safety and effectiveness is obtained through controlled clinical trials that have been executed in a disciplined, systematic, scientific manner and documented to state how to use the new product so that it will have the most beneficial effect. It might be worth examining whether all parties involved in this lengthy and expensive process adhere to these principles.
It should, perhaps, have been revealed that the previous commenter, Karel Patek, is the Vice President of Research & Development for a biopharmaceutical corporation. It is possible that his position in the pharmaceutical industry may bias his opinions regarding regulation of that industry.
It was stated that the FDA is remisss in their follow-up of post marketing studies. This and other omissions are not surprising: The agency has had a shortage of manpower for years due to inadequate budgets and an ever-increasing workload.
Just for the record....Imatinib is not approved for breast cancer. It is a wonderful drug which has revolutionised the way chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST) are managed. I do agree that the newer anticancer drugs are being tested using surrogate endpoints and not necessarily survival, which is the most robust efficacy assessment tool.
For sure, survival is a very robust efficacy assessment tool, but if it is also always “the best†remains to be debated. The patient’s quality of life is definitely more difficult to measure, but in my opinion just as important a consideration. Only the patient him/herself can decide if an increase in life expectancy (by a month, a year or whatever) is worth the side effects of a chemotherapy for example. Help, support and understanding with these difficult decisions combined into an individualistic approach are some of the reasons why CAM for example is so popular. Even though in many CAM treatments changes in surrogate markers have not been possible to be shown, they seem to fulfil a need by a significant number of patients. This discrepancy should not only be of scientific interest to psychologists but also to the field of medicine as a whole. It is all too often forgotten in general practice (and research) that surrogate markers are a compromise (or preliminary result) that should be further investigated (for example though outcome research). Otherwise the scientific basis of evidence based medicine could be considered disputable.