Generics as good as brand-name drugs when treating heart diseases

Dec 3 2008

Contrary to the perception of some patients and physicians, there is no evidence that brand-name drugs are clinically superior to their generic counterparts, according to an article in the December 3 issue of JAMA, the Journal of the American Medical Association, which examined studies comparing the effectiveness of generic vs. brand-name drugs for treating cardiovascular diseases.

"The problem of rising prescription drug costs has emerged as a critical policy issue, straining the budgets of patients and public/private insurers and directly contributing to adverse health outcomes by reducing adherence to important medications. The primary drivers of elevated drug costs are brand-name drugs, which are sold at high prices during a period of patent protection and market exclusivity after approval by the Food and Drug Administration (FDA)," the authors write. To control spending, many payers and clinicians have encouraged substitution of inexpensive bioequivalent generic versions of these drugs after the brand-name manufacturer's market exclusivity period ends.

Some patients and physicians have expressed concern that generic drugs may not be equivalent in their effectiveness. "Brand-name manufacturers have suggested that generic drugs may be less effective and safe than their brand-name counterparts. Anecdotes have appeared in the lay press raising doubts about the efficacy and safety of certain generic drugs," the authors note.

Aaron S. Kesselheim, M.D., J.D., M.P.H., of Brigham and Women's Hospital and Harvard Medical School, Boston, and colleagues assessed the clinical differences resulting from the use of generic medications or brand-name drugs used primarily to treat cardiovascular disease, which as a group make up the largest portion of outpatient prescription drug spending. The researchers conducted a meta-analysis on studies on this subject published from 1984 to August 2008, and to determine the expert opinion on the subject of generic substitution, also reviewed the content of editorials published during this time.

The researchers identified 47 articles for detailed analysis, covering nine different subclasses of cardiovascular drugs, of which 38 (81 percent) were randomized controlled trials (RCTs). Clinical equivalence was noted in 7 of 7 RCTs (100 percent) of beta-blockers, 10 of 11 RCTs (91 percent) of diuretics, 5 of 7 RCTs (71 percent) of calcium-channel blockers, 3 of 3 RCTs (100 percent) of antiplatelet agents, 2 of 2 RCTs (100 percent) of statins, 1 of 1 RCT (100 percent) of angiotensin-converting enzyme (ACE) inhibitors, and 1 of 1 RCT (100 percent) of alpha-blockers.

Among narrow therapeutic index drugs (NTI; drugs whose effective doses and toxic doses are separated by a small difference in plasma concentration), clinical equivalence was reported in 1 of 1 RCT (100 percent) of class 1 anti-arrhythmic agents and 5 of 5 RCTs (100 percent) of warfarin.

Forty-three editorials and commentaries were identified as meeting study criteria. Of these editorials, 23 (53 percent) expressed a negative view of the interchangeability of generic drugs compared with 12 (28 percent) that encouraged substitution of generic drugs (the remaining 8 did not reach a conclusion on interchangeability). Among editorials addressing NTI drugs specifically, 12 (67 percent) expressed a negative view while only 4 (22 percent) supported generic drug substitution.

"One explanation for this discordance between the data and editorial opinion is that commentaries may be more likely to highlight physicians' concerns based on anecdotal experience or other nonclinical trial settings. Another possible explanation is that the conclusions may be skewed by financial relationships of editorialists with brand-name pharmaceutical companies, which are not always disclosed. Approximately half of the trials in our sample (23/47, 49 percent), and nearly all of the editorials and commentaries, did not identify sources of funding," the researchers write.

The researchers also reported, "… we identified numerous studies that evaluated differences in clinical outcomes with generic and brand-name medications. Our results suggest that it is reasonable for physicians and patients to rely on FDA bioequivalence rating as a proxy for clinical equivalence among a number of important cardiovascular drugs, even in higher-risk contexts such as the NTI drug warfarin. These findings also support the use of formulary designs aimed at stimulating appropriate generic drug use. To limit unfounded distrust of generic medications, popular media and scientific journals could choose to be more selective about publishing perspective pieces based on anecdotal evidence of diminished clinical efficacy or greater risk of adverse effects with generic medications. Such publications may enhance barriers to appropriate generic drug use that increase unnecessary spending without improving clinical outcomes."

http://jama.ama-assn.org/