Establishing Therapeutic Equivalence of Complex Pharmaceuticals: The Case of Dabigatran.

Dabigatran is widely used for stroke prevention in atrial fibrillation. Dabigatran is no longer patent-protected in Canada and 2 generic formulations were recently approved by Health Canada. Branded dabigatran uses a complex formulation to maintain the acidic microenvironment required for maximal absorption. Consequently, food does not influence its bioavailability and the efficacy and safety of dabigatran are similar with or without concomitant intake of proton pump inhibitors (PPIs). Unfortunately, current bioequivalence criteria do not mandate testing of the generic formulations with food or with concomitant intake of PPIs; thus, the only data available for the approved generic products are in fasted, healthy volunteers. Without confirmation that the bioavailability of the generic dabigatran products is maintained in the presence of food or with coadministration of PPIs, it is uncertain whether they will afford patients the same protection from stroke as the branded product. Clinicians and patients must be made aware of this limitation to make informed prescribing decisions. The rules for establishing bioequivalence have not kept pace with the increasing complexity of pharmaceutical products; we urge regulators to update the regulatory process to ensure the therapeutic equivalence of generic products.

Aligning health care policy with evidence-based medicine: the case for funding direct oral anticoagulants in atrial fibrillation.

Misalignment between evidence-informed clinical care guideline recommendations and reimbursement policy has created care gaps that lead to suboptimal outcomes for patients denied access to guideline-based therapies. The purpose of this article is to make the case for addressing this growing access barrier to optimal care. Stroke prevention in atrial fibrillation (AF) is discussed as an example. Stroke is an extremely costly disease, imposing a significant human, societal, and economic burden. Stroke in the setting of AF carries an 80% probability of death or disability. Although two-thirds of these strokes are preventable with appropriate anticoagulation, this has historically been underprescribed and poorly managed. National and international guidelines endorse the direct oral anticoagulants as first-line therapy for this indication. However, no Canadian province has provided these agents with an unrestricted listing. These decisions appear to be founded on silo-based cost assessment-the drug costs rather than the total system costs-and thus overlook several important cost-drivers in stroke. The discordance between best scientific evidence and public policy requires health care providers to use a potentially suboptimal therapy in contravention of guideline recommendations. It represents a significant obstacle for knowledge translation efforts that aim to increase the appropriate anticoagulation of Canadians with AF. As health care professionals, we have a responsibility to our patients to engage with policy-makers in addressing and resolving this barrier to optimal patient care.