Tony W.Ho, Merck Research Laboratories, UG 4C-18, PO Box 1000, North Wales, PA 19454-1099tony_ho@merck.com
Kathryn M. Connor, Robert E. Shapiro, Hans-Christoph Diener, Sylvia Lucas, James Kost, Xiaoyin Fan, Kaiyin Fei, Christopher Assaid, Christopher Lines
Submitted November 20, 2009
Dr. Nardin questions the value of our second pivotal trial of telcagepant [1], stating that there were already sufficient data to support the superiority of telcagepant to placebo.
The regulatory approval process for new migraine medicines is rigorous and requires substantial evidence of efficacy and safety. This is usually achieved through conducting two well-controlled pivotal trials. At an alpha=0.05 level, there is a 1 in 20 risk of a false positive efficacy result within one trial. With two independent pivotal studies, the probability of a false positive in both studies is 1 in 400. Dr. Nardin states that “The publication of this trial raises serious concerns.” On the contrary, it would be a serious cause for concern if we had failed to publish it. In addition, the data were considered of high enough priority to publish.
Dr. Nardin mentions a possible study of patients with coronary artery or cerebrovascular disease. This study has recently been completed [4] and the results will be published. In addition to benefiting cardiovascular disease patients, CGRP receptor antagonists may benefit those intolerant of or poorly responsive to existing treatments due to the antagonists’ alternative mechanism.
Recent data suggest that only 19% of migraineurs use triptans over a one-year period. [5] This figure is low considering that 17% use opioid or barbiturate drugs, [5] which can result in migraine chronification [6] and may be associated with abuse/dependence concerns. These observations confirm that there are unmet treatment needs. CGRP receptor antagonists represent another choice for migraine sufferers.
Dr. Nardin also questions the sponsorship and authorship of our study. Novel medicines are developed by pharmaceutical companies in collaboration with academic experts and clinical investigators. Optimally, the process of developing pharmaceuticals that meet important medical needs should be guided by the clinical experiences of health care providers to help clarify those needs on behalf of patients.
Reasonable compensation of physicians for their efforts and expertise in drug development is appropriate as long as disclosure is transparent as was the case for our paper. We believe that a collaborative approach to developing new medicines serves the interests of patients.
References
4. Treatment of Migraine in Patients With Stable Vascular Disease. NCT00662818. Available at: http://www.clinicaltrials.gov/. Access October 18, 2009.
5. Bigal ME, Borucho S, Serrano D, Lipton RB. The acute treatment of episodic and chronic migraine in the USA. Cephalalgia 2009;29:891-897.
6. Bigal ME, Lipton RB. Excessive acute migraine medication use and migraine progression. Neurology 2008;71:1821-1828.
Disclosures: Drs. Connor, Kost, Fan, Fei, Assaid, Lines, and Ho are employees of, and own stock and/or stock options in, Merck & Co., Inc. Dr. Shapiro serves or has served on scientific advisory boards for, and received honoraria and funding for travel from Merck & Co, Inc., MAP Pharmaceuticals, and NuPathe; and has received research support from Merck & Co, Inc. and the NIH [NHLBI #R01HL71944 (Co-Investigator)]. Dr. Diener has received honoraria for participation in clinical trials, contribution to advisory boards or lectures from Addex Pharma, Allergan, Almirall, AstraZeneca, Bayer Vital, Berlin Chemie, Coherex Medical, CoLucid, Böhringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Grünenthal, Janssen-Cilag, Lilly, La Roche, 3M Medica , Minster, MSD, Novartis, Johnson & Johnson, Pierre Fabre, Pfizer, Schaper and Brümmer, SanofiAventis, and Weber & Weber; has received research support from Allergan, Almirall, AstraZeneca, Bayer, GSK, Janssen-Cilag, and Pfizer. Headache research at the Department of Neurology in Essen is supported by the German Research Council (DFG), the German Ministry of Education and Research (BMBF), and the European Union. Dr. Lucas has served on scientific advisory boards for GlaxoSmithKline, Merck & Co. Inc., and Bayer (formerly Berlex); has received honoraria from Allergan, GlaxoSmithKline, Merck & Co. Inc., EMD Serono, Biogen Idec, Pfizer, Endo, OMP, Teva Neuroscience, the National Multiple Sclerosis Society, and Headache Cooperative of the Pacific; has served on the speaker's bureaus of GlaxoSmithKline, Merck & Co. Inc., EMD Serono, Biogen Idec, and Pfizer; has received research support from GlaxoSmithKline, Merck & Co. Inc., Allergan, Nupathe, MAP, Biogen Idec, Sanofi-Aventis, and AGA.
Dr. Nardin questions the value of our second pivotal trial of telcagepant [1], stating that there were already sufficient data to support the superiority of telcagepant to placebo.
The regulatory approval process for new migraine medicines is rigorous and requires substantial evidence of efficacy and safety. This is usually achieved through conducting two well-controlled pivotal trials. At an alpha=0.05 level, there is a 1 in 20 risk of a false positive efficacy result within one trial. With two independent pivotal studies, the probability of a false positive in both studies is 1 in 400. Dr. Nardin states that “The publication of this trial raises serious concerns.” On the contrary, it would be a serious cause for concern if we had failed to publish it. In addition, the data were considered of high enough priority to publish.
Dr. Nardin mentions a possible study of patients with coronary artery or cerebrovascular disease. This study has recently been completed [4] and the results will be published. In addition to benefiting cardiovascular disease patients, CGRP receptor antagonists may benefit those intolerant of or poorly responsive to existing treatments due to the antagonists’ alternative mechanism.
Recent data suggest that only 19% of migraineurs use triptans over a one-year period. [5] This figure is low considering that 17% use opioid or barbiturate drugs, [5] which can result in migraine chronification [6] and may be associated with abuse/dependence concerns. These observations confirm that there are unmet treatment needs. CGRP receptor antagonists represent another choice for migraine sufferers.
Dr. Nardin also questions the sponsorship and authorship of our study. Novel medicines are developed by pharmaceutical companies in collaboration with academic experts and clinical investigators. Optimally, the process of developing pharmaceuticals that meet important medical needs should be guided by the clinical experiences of health care providers to help clarify those needs on behalf of patients.
Reasonable compensation of physicians for their efforts and expertise in drug development is appropriate as long as disclosure is transparent as was the case for our paper. We believe that a collaborative approach to developing new medicines serves the interests of patients.
References
4. Treatment of Migraine in Patients With Stable Vascular Disease. NCT00662818. Available at: http://www.clinicaltrials.gov/. Access October 18, 2009.
5. Bigal ME, Borucho S, Serrano D, Lipton RB. The acute treatment of episodic and chronic migraine in the USA. Cephalalgia 2009;29:891-897.
6. Bigal ME, Lipton RB. Excessive acute migraine medication use and migraine progression. Neurology 2008;71:1821-1828.
Disclosures: Drs. Connor, Kost, Fan, Fei, Assaid, Lines, and Ho are employees of, and own stock and/or stock options in, Merck & Co., Inc. Dr. Shapiro serves or has served on scientific advisory boards for, and received honoraria and funding for travel from Merck & Co, Inc., MAP Pharmaceuticals, and NuPathe; and has received research support from Merck & Co, Inc. and the NIH [NHLBI #R01HL71944 (Co-Investigator)]. Dr. Diener has received honoraria for participation in clinical trials, contribution to advisory boards or lectures from Addex Pharma, Allergan, Almirall, AstraZeneca, Bayer Vital, Berlin Chemie, Coherex Medical, CoLucid, Böhringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Grünenthal, Janssen-Cilag, Lilly, La Roche, 3M Medica , Minster, MSD, Novartis, Johnson & Johnson, Pierre Fabre, Pfizer, Schaper and Brümmer, SanofiAventis, and Weber & Weber; has received research support from Allergan, Almirall, AstraZeneca, Bayer, GSK, Janssen-Cilag, and Pfizer. Headache research at the Department of Neurology in Essen is supported by the German Research Council (DFG), the German Ministry of Education and Research (BMBF), and the European Union. Dr. Lucas has served on scientific advisory boards for GlaxoSmithKline, Merck & Co. Inc., and Bayer (formerly Berlex); has received honoraria from Allergan, GlaxoSmithKline, Merck & Co. Inc., EMD Serono, Biogen Idec, Pfizer, Endo, OMP, Teva Neuroscience, the National Multiple Sclerosis Society, and Headache Cooperative of the Pacific; has served on the speaker's bureaus of GlaxoSmithKline, Merck & Co. Inc., EMD Serono, Biogen Idec, and Pfizer; has received research support from GlaxoSmithKline, Merck & Co. Inc., Allergan, Nupathe, MAP, Biogen Idec, Sanofi-Aventis, and AGA.