Research report Are subjects in treatment trials of panic disorder representative of patients in routine clinical practice? Results from a national sample Nicolas Hoertel a,b,n , Yann Le Strat a,b,c , Pierre De Maricourt b , Fre ´ de ´ ric Limosin b,d , Caroline Dubertret a,b,c a AP-HP, Hˆ opital Louis Mourier, Service de psychiatrie et addictologie, 178 Rue Renouillers, Colombes Cedex 92701, France b INSERM UMR 894, Centre Psychiatrie et Neurosciences, Univ. Paris Descartes, PRES Sorbonne Paris Cite´, Paris, France c Univ. Paris Diderot, PRES Sorbonne Paris Cite ´, Faculte´ de me´decine Bichat-Lariboisi  ere, Paris, France d AP-HP, Hˆ opital Corentin-Celton, Service de psychiatrie, 92130 Issy-les-Moulineaux, France, Univ. Paris Descartes, PRES Sorbonne Paris Cite´, Paris, France article info Article history: Received 25 May 2012 Received in revised form 25 September 2012 Accepted 25 September 2012 Keywords: Generalizability Panic disorder Clinical trials Eligibility criteria National epidemiologic survey on alcohol and related conditions (NESARC) abstract Background: Research on the generalizability of clinical trials in panic disorder is limited. The present study sought to quantify the generalizability of clinical trials’ results of individuals with DSM-IV panic disorder (PD) to a large community sample. Methods: Data were derived from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a large national representative sample of 43,093 adults of the United States population. We applied a standard set of eligibility criteria representative of PD clinical trials to all adults with past 12 months PD (n ¼907), and then to a subgroup of participants seeking treatment (n ¼105). Our aim was to determine the proportion of participants with PD who would have been excluded by typical eligibility criteria. Results: We found that more than 8 out of ten participants (80.52%; 95% CI ¼77.13–83.52%) with PD were excluded by at least one criterion. In the subgroup of participants who sought treatment, the exclusion rate by at least one criterion was higher (92.40%; 95% CI ¼84.60–96.42%). For the full sample and the treatment-seeking subsample, having currently a depression and a diagnosis of alcohol or drug abuse/dependence were the criteria excluding the highest percentage of participants. Having a lifetime history of bipolar disorder and a current significant medical condition also excluded a substantial proportion of individuals in both samples. Exclusion rates were similar when considering panic disorder with and without agoraphobia. Conclusions: Clinical trials, that exclude a majority of adults with panic disorder, should carefully consider the impact of eligibility criteria on the generalizability of their results. As required by CONSORT guidelines, reporting exclusion rate estimate and reasons of eligibility should be mandatory in both clinical trials and meta-analyses. & 2012 Elsevier B.V. All rights reserved. 1. Introduction Clinical study applied strict eligibility criteria that excluded patients with comorbid psychiatric and addictive disorders to eval- uate efficacy of the treatment on the disorder under study. However, restrictive eligibility criteria may affect the external validity of clinical studies (Weisberg et al., 1996) and result in a selection bias (Humphreys et al., 2008), perpetuating the gap between research and clinical practice (Dzewaltowski et al., 2004). As a result, concerns have emerged regarding whether results from tightly controlled clinical trials generalize to patients, who may often present with complex clinical presentations in community settings. The impact of exclusion criteria on the generalizability of clinical trials has been described for antidepressants (Blanco et al., 2008a; Gaynes et al., 2009; Zimmerman et al., 2002, 2005) and antipsychotics efficacy trials (Boter et al., 2010; Khan et al., 2005; Leucht et al., 2008), and clinical trials for alcohol dependence (Blanco et al., 2008b; Humphreys et al., 2005, 2007), cannabis dependence (Okuda et al., 2010), nicotine dependence (Le Strat et al., 2011), and generalized anxiety disorder (Hoertel et al., 2012). Previous studies concluded that the percentage of participants excluded by these criteria ranged from 50.5% to 75.8% (Blanco et al., 2008a, 2008b), suggesting that clinical trials, which are designed to comply with guidelines by regulatory agencies, exclude a substantial proportion of patients with other disorders or significant medical problems. Contents lists available at SciVerse ScienceDirect journal homepage: www.elsevier.com/locate/jad Journal of Affective Disorders 0165-0327/$ - see front matter & 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jad.2012.09.023 n Corresponding author at: Hˆ opital Louis Mourier, Service de psychiatrie, Assistance Publique-H ˆ opitaux de Paris (AP-HP), 178 Rue Renouillers, 92701 Colombes cedex, France. Tel.: 33 1 47 60 68 76; fax: 33 1 47 60 67 40. E-mail address: nico.hoertel@yahoo.fr (N. Hoertel). Please cite this article as: Hoertel, N., et al., Are subjects in treatment trials of panic disorder representative of patients in routine clinical practice? Results from a national sample. Journal of Affective Disorders (2012), http://dx.doi.org/10.1016/j.jad.2012.09.023 Journal of Affective Disorders ] (]]]]) ]]]–]]]