What can we learn from clinical trials of anticonvulsant drugs in epilepsy?
Any physician who intends to utilize the available antiepileptic drugs (AEDs) judiciously, cannot do so without being well versed on their pharmacological properties and the large body of evidence that is continuously accumulating on their relative efficacy and tolerability in different types of epilepsy. While informal observations such as retrospective surveys and case reports can be useful under special circumstances, prospective randomized clinical studies represent by far the most important tool by which objective information can be obtained about the clinical value of existing drugs. Even randomized trials, however, can produce misleading conclusions because of inherent weaknesses or bias in study design, analysis, and interpretation. Common deficiencies identified in some of the most recent drug trials in epilepsy include 1) inclusion of inappropriately heterogeneous patient groups (for example, patients with partial and primarily generalized seizures); 2) low statistical power due to insufficient sample size (for trials designed to show therapeutic equivalence); 3) inappropriate titration rates or suboptimal dosages or dosing schedules (often favouring the sponsor's product over the comparator); 4) insufficient duration of treatment; and 5) utilization of endpoints of questionable clinical significance. In part, some of the above shortcomings can be ascribed to the fact that most clinical drug trials are designed to address regulatory needs rather than to provide the type of information required for rational prescribing. Physicians need to be alerted about the importance of these issues, and they should make every possible effort to interpret critically the medical literature on which they rely to guide and support their therapeutic decisions.
Perucca
Emilio
E
Clinical Pharmacology Unit, Department of Internal Medicine and Therapeutics, University of Pavia, Piazza Botta 10, 27100 Pavia, Italy. perucca@unipv.it
D000927:Anticonvulsants / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards*; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy*; D004992:Ethics, Medical; D006801:Humans; D015201:Meta-Analysis as Topic; D010919:Placebos / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards
D000927:Anticonvulsants; D010919:Placebos