Efficacy of new drugs compared to older ones not dramatic, study says

The effectiveness of new drugs compared with that of older drugs has fallen since the 1970s, according to a new study in Health Affairs.

In the study, researchers randomly selected and analyzed the results of 315 clinical trials that compared a drug to a placebo from 4 medical journals: New England Journal of Medicine, Journal of the American Medical Association, Lancet, and British Medical Journal between 1966 and 2010.

The data extraction was done by research assistants who were kept blind to the purpose of the study and all studies were independently reviewed by 2 different research assistants. Drugs to treat cardiovascular disease, cancer, mental disorders, and respiratory illness, were included.

Researchers found that the average effect size, as measured by the odds ratio (which compares the odds of an outcome resulting from the treatment to the odds of that outcome in absence of the treatment), decreased from a peak of 4.51 (1971-1980) to 1.36 (2001-2010).

"In other words, there has been a significant decline over time in the extent to which new drug treatments have been shown to be significantly more effective than placebos to the point that in recent years the average study found only small differences between the active drug and placebo," said lead author Mark Olfson, professor of clinical psychiatry at Columbia University and a research psychiatrist at the New York State Psychiatric Institute, in New York City.

"The results suggest that medical breakthroughs of the sort that confer large benefits above placebo are becoming less common," said Dr. Olfson. "An awareness of the uncommonness of these transformational drug discoveries helps to calibrate expectations for future placebo-clinical trials. 

"With apparently declining yield from placebo-controlled studies, now may be a good time to place greater emphasis on studies comparing 2 or more drugs that are known to be effective to evaluate whether there are meaningful differences between them in their tolerability, adherence, safety, or costs," Dr. Olfson contined.

According to Randy Vogenberg, managing principal of Bentelligence, and adjunct professor of pharmacy management at the University of Rhode Island, Kingston, R.I., many plans and PBMs already have been looking to maximize generic or "older" therapies over the last few years.

"Purchasers of healthcare are less involved in the clinical details but similarly have sought to reduce the cost trend or 'bend the cost curve' due to economic pressures from the recession," Vogenberg said. "As part of the riding the generic wave, plans and PBMs have become increasingly aggressive in promoting step therapy strategies as well as optimizing first-line generic-only treatments."

Now that providers are in shared or full-risk arrangements on commercial and exchange/Medicare plan products, they too have been rethinking treatment strategies, according to Vogenberg. "One of the best examples has been in oncology where the minimal incremental clinical benefit versus the increasingly higher per product cost is resulting in greater use of first-line generic treatments for most patients which deliver good outcomes. This is especially true now that earlier diagnoses and treatment is so common," he said.

"Interestingly, these approaches do align patient interests along with the provider and purchaser of coverage-employer, union, and municipality- better than in the past," Vogenberg continued. "I expect that the successes in oncology will move into immunology-rheumatoid arthritis, multiple sclerosis-quickly as large medical groups and ACOs seek to maximize outcomes at the lowest cost possible for pharmacologic therapies."