Concerns Over Off-Label Prescribing of Medications

Investigation by McGill University Researchers

Concerns are emerging regarding the clinical effectiveness of off-label prescribing. Researchers from McGill University examined whether the off-label use of prescription drugs is backed by substantial research. Pharmaceutical companies primarily aim to gain approval from the Food and Drug Administration (FDA) to market their drugs. The FDA grants approval only after confirming a drug’s safety and efficacy through clinical trials for at least one indication. Following this, additional uses of the drug are investigated to broaden its applications.

Lack of Incentives for Further Research

Once a drug receives FDA approval, pharmaceutical companies have little motivation to conduct further costly clinical trials. Additionally, physicians may prescribe off-label uses based on relatively inexpensive exploratory studies. This practice raises significant concerns about the clinical effectiveness of off-label prescriptions.

Study on Pregabalin

Researchers at McGill University’s Biomedical Ethics Unit in Montreal focused on the off-label prescribing of pregabalin. This drug is approved for treating nerve pain and as an adjunctive treatment for partial onset seizures in adults. Off-label uses of pregabalin include conditions such as generalized anxiety disorder, lower back pain, essential tremor, migraine, post-surgery pain, itchiness, restless legs syndrome, and vasomotor menopausal symptoms. The team analyzed over 230 clinical trials regarding pregabalin’s efficacy, with findings published in JAMA Internal Medicine.

Findings from Clinical Trials

Among the 33 new indications evaluated, more than half were only studied in exploratory trials. Most of these trials were exploratory in nature, with 61% reporting positive outcomes. However, confirmatory studies are essential to validate the safety and efficacy of these indications through larger sample sizes. The analysis indicated that the majority of research conducted on pregabalin’s alternative uses focused on exploration rather than conclusive evidence of its effectiveness and safety.

Consequences of Incomplete Research

Relying on exploratory studies without subsequent confirmatory trials can lead healthcare providers to prescribe medications based on inadequate evidence. In the reviewed analysis, 63% of exploratory studies were not followed by confirmatory research within five years of publication. This leaves physicians, patients, and the healthcare system with incomplete information while potentially endorsing effective off-label uses of pregabalin.

Ethical Implications and Recommendations

An example of concern arises from the off-label prescribing of pregabalin for lower back pain. Despite the absence of appropriate confirmatory studies, pregabalin is frequently used for this condition. Prescribing ineffective treatments or drugs with unverified indications poses ethical dilemmas. Unfortunately, funding for large-scale confirmatory trials diminishes after a drug’s initial approval. The case of pregabalin illustrates potentially inappropriate off-label uses based on preliminary studies.

The researchers from McGill University urge ethics committees, drug regulators, funding organizations, and healthcare payers to utilize their influence to promote confirmatory testing for off-label indications of prescription drugs.

References

Federico CA, Wang T, Doussau A, Mogil JS, Fergusson D, Kimmelman J. Assessment of Pregabalin Post-approval Trials and the Suggestion of Efficacy for New Indications: A Systematic Review. JAMA Intern Med. 2018.
Pregabalin. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com. Accessed November 29, 2018.