It now takes 10-15 years for a pharmaceutical company to get a new drug approved, and on average the cost exceeds $1 billion. There is a lengthy process of laboratory, animal and clinical studies, and then regulatory review, to establish safety and effectiveness according to government standards. Arguably, that is more than enough.
Yet skeptics continue to question the need for many new drugs that make it through the exceedingly rigorous gauntlet. Dr. Marcia Angell, the former editor of the New England Journal of Medicine, has complained for years that most new drugs are only minor variations of old ones, "me-too" drugs, which she has said are "unlikely to be better than existing ones for the same condition." Drs. Donald Light and Joel Lexchin wrote in 2012 for BMJ (formerly the British Medical Journal) about an "innovation crisis" brought on because "pharmaceutical research and development turns out mostly minor variations on existing drugs." Rosanne Spector, the editor of Stanford Medicine, similarly charged in 2005 that pharmaceutical companies "chemically rejigger an oldie but goodie, craft a new name, mount a massive advertising campaign and sell the retread as the latest innovative breakthrough."
Such criticisms are misleading and ignore several compelling reasons why a new drug on the market—even one that appears from initial clinical trials to be no better than the alternatives—may prove valuable.
First, there often are critical differences in clinical safety or effectiveness among drugs that act through similar mechanisms. A study of the interactions of cholesterol-lowering statins, to be published in the forthcoming issue of the Journal of Clinical Lipidology, found that patients who also took other medications that inhibit the metabolism of statins—which has the effect of increasing the statin concentration in the blood—were more likely to have muscle pain that caused them to stop taking the statin. Discontinuing the statin puts them at higher risk of cardiovascular disease. The study also revealed that some formulations of statins were more likely to cause patients to experience side effects, making it critical for clinicians to select statins in a way that minimizes adverse interactions with other drugs.
Second, even if two drugs are each effective in 40% of patients with a particular symptom or disease, each of them may not work in the same 40%. If the drugs are effective in different populations, the unavailability of the second drug could deprive a large number of patients of the medicine they really need.
Practicing physicians know that for certain conditions—such as treating pain or the symptoms of multiple sclerosis, or to prevent blood clots—patients whose conditions seem indistinguishable from one another sometimes do better on different drugs. Having alternatives—"me-too drugs"—is in the best interests of patients.
Third, "supplemental," or secondary, approvals of drugs—which include new dosages, formulations and uses—account for "a substantial share of drug utilisation and associated economic and medical benefits," according to a 2006 study of three important classes of medicines by MIT economist Ernst Berndt and his collaborators. Another analysis, published in 2011 by Joseph DiMasi of the Tufts Center for the Study of Drug Development, found that the number of new or modified FDA-approved uses of previously approved drugs increased 17% from 1998-2003 to 2004-09.
This suggests that if regulators had denied approval because initial studies failed to show the drug's superiority to others already on the market, these later benefits would have been missed. Consider the therapeutic protein interferon alfa-2a, sold as Roferon-A. It was first approved in 1986 to treat a rare blood condition called hairy cell leukemia. It is now seldom used for that disease but was later found effective for such conditions as chronic hepatitis C and myelogenous leukemia. If the drug had been denied the initial marketing approval because other drugs already were available for hairy cell leukemia, its more important uses probably wouldn't have been discovered.
Fourth, in a study in the journal Nature Reviews Drug Discovery in 2011, Joseph DiMasi and Laura Faden of the Tufts Center for the Study of Drug Development persuasively debunked the myth that drug companies purposely produce duplicative me-too drugs. They closely examined drug-development patterns and timing and found that the process is best viewed as "a race in which several firms pursue investigational drugs with similar chemical structures or with the same mechanism of action before any drug in the class obtains regulatory marketing approval." In other words, companies are not starting out to develop a me-too product any more than a marathon runner starts a race intending to be an also-ran.
These findings inform the discussion about the value of me-too drugs far more than the complaints of those who fail to appreciate the nuances of drug development and treatment.
Dr. Miller, a physician and molecular biologist, is the fellow in Scientific Philosophy and Public Policy at Stanford University's Hoover Institution. He was the founding director of the FDA's Office of Biotechnology.
