Clinical Trials May Lead to Worse Medicine

'Best practices' in medicine are based on clinical trials, which are supposedly at the highest level of evidence. But instead of bringing sound science into drug testing, clinical trials have brought a neglect of patients' individual needs and an epidemic of over-prescribing, writes Henry Bauer, PhD, in the fall issue of the Journal of American Physicians and Surgeons.

The benefits of vaccination or antibiotics are readily confirmed in clinical trials because the desired outcomes are plainly evident: how many people get sick or die. But with chronic conditions treated with today's 'blockbuster' drugs, it would take decades to show outcomes such as longer lifespan or manifestly less debility. Therefore, surrogate outcomes are looked at since approval of drugs can be based on trials as short as 6 months.

Such measures include blood pressure and cholesterol levels as surrogates for cardiovascular disease, blood sugar for diabetes, and bone density measures for fracture prevention. The trouble is that these surrogate biomarkers are not in fact valid representatives of the ailments for which they stand, Bauer states. They are merely statistical associations.

It is assumed that altering the biomarker could alter the chance of progression to manifest illness. "This amounts to treating symptoms as though they were the underlying disease," Bauer writes. The presumed benefits from widespread use of statins, antihypertensives, and bisphosphonates have not been realized in practice, according to retrospective studies and meta-analyses.

Drugs that globally have a statistically significant benefit might actually harm an individual patient. But increasingly bureaucratic healthcare systems influence doctors to follow guidelines based on clinical trials as mandates rather than as suggestions. If they deviate from "standard" practice to better serve individuals, physicians experience tangible personal risks.

Previously, physicians often started with the lowest possible dose. But clinical trials may seek to find the largest tolerable dose, to identify the 'treatment-limiting toxicity', instead of the lowest useful dose.

The "average" result of trials is often inappropriate for individual patients. Even worse, Bauer writes, "conclusions are drawn on the basis of statistical significance and not on what the magnitude of a possible benefit might be, and how it compares to the incidence of side effects."

He concludes: "The apparently 'scientific' status of guidelines based on clinical trials has undermined properly individualized attention to the case of every individual patient."