Medicine in the dark

Some doctors treat patients with early-stage prostate cancer with radiation. Others favor surgery, while some advocate only close monitoring. Which approach is most successful? No one knows.

When it comes to diabetes management, doctors don’t have answers to key questions: At what point should insulin be started? Is it safe to lower the blood sugar to normal levels? What is the best way to monitor blood sugar control?

Similarly, endocrinologists don’t know what is the best way to treat patients with hyperactive thyroids. Doctors in Europe typically use medications, while those in the U.S. more frequently give radioactive iodine. Only limited evidence is available to guide the decision.

It may seem perplexing that there is so much uncertainty about these relatively simple questions. All of the above treatments have been around for decades. Shouldn’t we have definitive answers by now?


In this week’s issue of the Journal of the American Medical Assn., we report the results of a study that may help explain why we don’t. In the study, we analyzed 328 medication studies recently published in six top medical journals and found that just 32% were aimed at determining which available treatment is best. The rest were either aimed at bringing a new therapy to market or simply compared a medication with a placebo. Whether the therapy was better or worse than other treatments was simply not addressed.

Research involving new therapies is of course crucial for medical progress, but there is also a need for research that compares the effectiveness of the rapidly growing array of existing therapies and approaches.

So why, then, did only a third of medication studies focus on helping doctors use existing therapies more effectively? The answer lies in the fact that pharmaceutical companies fund nearly half of all medication research, including the lion’s share of large clinical trials. For obvious reasons, commercially funded research is primarily geared toward the development of new and marketable medications and technologies. Once these products have won approval for clinical use, companies no longer have incentives to study exactly how and when they should be used.

In support of this claim, we found that 87% of the comparative effectiveness studies we analyzed were funded entirely or in part by non-commercial sources, such as nonprofit foundations or government institutions. In addition, 91% of studies comparing medications with non-pharmacologic therapies (such as surgery or lifestyle changes) received non-commercial funding, as did 94% of studies comparing different medication strategies (such as different blood sugar targets in patients with diabetes) and 90% of studies comparing the safety profiles of medications. Non-commercial sources funded 100% of studies comparing the cost- effectiveness of different treatments, though only 2% of the studies we reviewed included such analysis.

Congress recently appropriated more than $1 billion in the American Recovery and Reinvestment Act to promote comparative effectiveness research. This is a good first step, but the money will need to be spent carefully. We believe studies that address fundamental clinical decisions -- such as when to use medications versus surgery or how to use therapies more effectively -- should be favored over those that simply compare two alternative medications. There is also clearly a need for more research on the comparative safety and costs of different treatments. And although many researchers are thankful for the new research funds, it may soon become apparent that $1 billion is far from sufficient.

Reform is also necessary to ensure that commercially funded research is designed in a way that is more helpful to doctors. Our study showed that two-thirds of commercially funded randomized trials compared medications with a placebo rather than with another active therapy. Though placebos are appropriate when no alternative therapies are available, in many of the trials we examined, we suspect alternative therapies could have been used instead. For this reason, we believe that regulatory agencies such as the Food and Drug Administration should only approve new therapies that have been shown to be at least as good as existing therapies whenever such alternatives exist. Alternatively, though more controversial, some experts have proposed that pharmaceutical companies should be allowed to fund -- but not design -- clinical studies.

As medical science advances, clinical decision-making will only become more complex. Only by expanding public funding for comparative effectiveness research can we hope to put existing medical treatments and healthcare services to their best use. Doing so would ensure that national research priorities are determined by patient needs rather than by corporate agendas.

Michael Hochman, MD, is an assistant professor of clinical medicine at USC’s Keck School of Medicine. Danny McCormick, MD, MPH, is an assistant professor of medicine at Harvard Medical School.