Challenges of therapeutic substitution of drugs for economic reasons: focus on CVD prevention

Abstract

Background:

Healthcare systems throughout the world are under increasing pressure to control and minimise costs. The substitution of initially-prescribed drugs with cheaper equivalents is an obvious option which presents a rapid and visible means to reduce these costs. Whether the substitution improves patient and/or population outcomes must be appraised and this paper highlights the conditions under which therapeutic substitution may require additional thought and consideration.

Scope:

In this paper, some of the medical evidence and the regulatory environment for and against the three types of therapeutic substitution – generic, within-class and between-class – are discussed. This article is not an exhaustive review of the literature, but captures some of the key clinical, pharmacological, economic, policy and ethical issues regarding generic and therapeutic substitution. Search criteria of the most commonly used terms, i.e. therapeutic substitution, switching, interchange, and bioequivalence, were applied to Embase, PubMed and Google Scholar to identify relevant publications.

Findings:

Although population studies support therapeutic substitution in principle, there is evidence that substitution may not always result in therapeutic equivalence in individual patients, with the consequent potential for greater risks of decreased efficacy and/or increased safety concerns. Factors such as patient choice and therapeutic equivalence also play an important role in the effectiveness of the treatment and overall management of the patient. The pan-European regulatory environment provides another contradiction, encouraging widespread cost containment through reduction in drug acquisition costs, while simultaneously promoting an increased role for patients in defining and managing their own treatment.

Conclusions:

There is a strong rationale for careful management in some patients with cardiovascular disease. Treatment decisions should be transparent and based on strong clinical evidence. If not, drug substitution on economic grounds alone cannot be considered to be in the individual patient’s interest and is therefore unethical.

Key words::

• Cost control
• Cost savings
• Drug cost
• Generic drugs
• Substitution
• Switching
• Therapeutic equivalency

Transparency

Declaration of funding

The writing of this manuscript has been supported by, but without interference from, Novartis Pharmaceuticals AG, Basel, Switzerland.

Declaration of financial/other relationships

The author has disclosed that he has received reimbursements, fees and funding from many pharmaceutical companies, including Abbott, Astellas, AstraZeneca, Baxter, Fujisawa, Genzyme, Roche, sanofi aventis, Sterling Winthrop and Wyeth. He has also disclosed that he has served as a consultant to Novartis, Baster and Astellas, and that he is on the speakers’ bureau of Novartis, Roche, AstraZeneca, Baxter and Astellas. He owns stock in Novartis, Roche, AstraZeneca, Baxter, Abbott and Genzyme.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgment

The author thanks Sandie Lowery, Manu Field and Karen Wilson-Smith for editorial support during development of this manuscript.