Letters

superior alternatives seems like a better strategy than removing benzodiazepines from the pharmacopeia before these optimized alternatives arrive. John H. Krystal, MD Scott Stossel, BA Andrew D. Krystal, MD Author Affiliations: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut (J. H. Krystal); Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut (J. H. Krystal); Clinical Neuroscience Division, VA National Center for Posttraumatic Stress Disorder, VA Connecticut Healthcare System, West Haven (J. H. Krystal); Yale– New Haven Hospital, New Haven, Connecticut (J. H. Krystal); The Atlantic, Washington, DC (Stossel); Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina (A. D. Krystal); Duke Clinical Research Institute, Durham, North Carolina (A. D. Krystal). Corresponding Author: John H. Krystal, MD, Department of Psychiatry, Yale University School of Medicine, 300 George St, Ste 901, New Haven, CT 06511 ([email protected]). Published Online: April 29, 2015. doi:10.1001/jamapsychiatry.2015.0351. Conflict of Interest Disclosures: Dr J. H. Krystal has served as a consultant for AbbVie Inc (formerly Abbott Laboratories), Amgen, Astellas Pharma Global Development Inc, AstraZeneca Pharmaceuticals, Biomedisyn Corp, Bristol-Myers Squibb, Eli Lilly and Co, Euthymics Bioscience Inc, Neurovance Inc (a subsidiary of Euthymics Bioscience), Janssen Research and Development, Lundbeck Research USA, Novartis Pharma AG, Otsuka America Pharmaceutical Inc, Sunovion Pharmaceuticals Inc, and Takeda Industries. He has served on the scientific advisory boards of Lohocla Research Corp, Mnemosyne Pharmaceuticals Inc, Naurex Inc, and Pfizer Pharmaceuticals. Dr J. H. Krystal holds stock in Biohaven Medical Sciences and stock options in Mnemosyne Pharmaceuticals Inc and Biohaven Medical Sciences. He serves on the editorial board as editor of Biological Psychiatry and holds patents related to dopamine and noradrenergic reuptake inhibitors in the treatment of schizophrenia, glutamate-modulating agents in the treatment of mental disorders, and intranasal administration of ketamine to treat depression in the United States. Dr A. D. Krystal has received grant/research support from Teva Pharmaceutical Industries, Sunovion, Astellas Pharma, NeoSync, Brainsway, Janssen Pharmaceuticals, ANS–St Jude Medical, Novartis, Azevan Pharmaceuticals, and Eisai. He has also served as a consultant for Abbott, AstraZeneca, Attentiv, Teva Pharmaceutical Industries, Eisai, Eli Lilly and Co, Jazz Pharmaceuticals, Janssen Pharmaceuticals, Merck, Neurocrine Biosciences, Novartis, Otsuka America Pharmaceutical Inc, Pfizer, Lundbeck, Roche, Sunovion, Paladin, Pernix Therapeutics, and Transcept Pharmaceuticals. No other disclosures were reported. Funding/Support: Dr A. D. Krystal has received grant/research support from the National Institutes of Health. Role of the Funder/Sponsor: The National Institutes of Health had no role in the preparation, review, or approval of the manuscript, and the decision to submit the manuscript for publication. 1. Moore N, Pariente A, Bégaud B. Why are benzodiazepines not yet controlled substances? JAMA Psychiatry. 2015;72(2):110-111. 2. Krystal AD. A compendium of placebo-controlled trials of the risks/benefits of pharmacological treatments for insomnia: the empirical basis for US clinical practice. Sleep Med Rev. 2009;13(4):265-274. 3. Morin CM, Colecchi C, Stone J, Sood R, Brink D. Behavioral and pharmacological therapies for late-life insomnia: a randomized controlled trial. JAMA. 1999;281(11):991-999. 4. Roth T, Walsh JK, Krystal A, Wessel T, Roehrs TA. An evaluation of the efficacy and safety of eszopiclone over 12 months in patients with chronic primary insomnia. Sleep Med. 2005;6(6):487-495. 5. Krystal AD, Walsh JK, Laska E, et al. Sustained efficacy of eszopiclone over 6 months of nightly treatment: results of a randomized, double-blind, placebo-controlled study in adults with chronic insomnia. Sleep. 2003;26(7): 793-799. 6. Nagy LM, Krystal JH, Woods SW, Charney DS. Clinical and medication outcome after short-term alprazolam and behavioral group treatment in panic disorder: 2.5-year naturalistic follow-up study. Arch Gen Psychiatry. 1989;46(11): 993-999. jamapsychiatry.com

A More Robust Test of the Penrose Hypothesis To the Editor Mundt et al1 should be applauded for attempting to bring new data to bear on a research question of substantive policy significance. However, we are concerned that their analysis overlooked a point of critical significance. While they argued that their findings “cannot be explained by a simple overall trend to reduce numbers of beds and increase prison populations,” they failed to adjust for secular changes in the underlying determinants of crime.2 Neither did Lamb,3 who argued in the accompanying editorial that longitudinal data are needed to appropriately test the Penrose hypothesis, comment on the need to do so. Such adjustment would be considered standard practice in the analysis of panel data,4 particularly given the challenges of drawing causal inferences from cross-national panel data.5 Using the information reported in Figures 1 and 2 in the article by Mundt et al,1 we reconstructed the authors’ data set (data and Stata code available on request). Fitting the same regression model with country fixed effects and robust standard errors, we replicated the authors’ main finding to a close approximation (β = −5.11; 95% CI, −6.61 to −3.60; P < .001). After adding year fixed effects to the model, the estimated association between beds and prisoners was reduced in magnitude by more than 80%, was not statistically significant, and the lower confidence limit nearly excluded the upper confidence limit of the authors’ point estimate (β = −1.09; 95% CI, −3.37 to 1.19; P = .27). Adding a linear time trend instead of year fixed effects yielded a similar result (β = −1.02; 95% CI, −3.49 to 1.46; P = .34), suggesting that the weakened association cannot simply be attributed to the degree-of-freedom demands of the year fixed effects. The correlation between beds and the linear time trend was relatively low (Spearman ρ = −0.38; 95% CI, −0.59 to −0.13), with the linear time trend explaining little of the variation in beds (R2 = 0.23). Thus, our finding cannot simply be attributed to collinearity between the 2 variables. Consistent with this argument, Figure 1 in the article by Mundt et al1 shows that the rates of change in beds differ for each country. Therefore, accounting for average sample time trends should not have attenuated the association between beds and prisoners if the association were (contrary to fact) robust. Even if our conclusion were simply driven by collinearity, it would not absolve the authors of their responsibility to adjust their estimates for secular trends.4 The Penrose hypothesis does not appear to be supported in these data. Alexander C. Tsai, MD, PhD Atheendar S. Venkataramani, MD, PhD Author Affiliations: Chester M. Pierce, MD, Division of Global Psychiatry, Massachusetts General Hospital, Boston (Tsai); Mbarara University of Science and Technology, Mbarara, Uganda (Tsai); Center for Global Health, Massachusetts General Hospital, Boston (Tsai, Venkataramani); Department of Medicine, Massachusetts General Hospital, Boston (Venkataramani). Corresponding Author: Alexander C. Tsai, MD, PhD, Massachusetts General Hospital, 100 Cambridge St, 15th Floor, Boston, MA 02114 ([email protected]). Published Online: May 6, 2015. doi:10.1001/jamapsychiatry.2015.0212. Conflict of Interest Disclosures: None reported. (Reprinted) JAMA Psychiatry July 2015 Volume 72, Number 7

Copyright 2015 American Medical Association. All rights reserved.

Downloaded From: http://archpsyc.jamanetwork.com/ by a Central Michigan University User on 09/24/2015

735

Letters

Funding/Support: The authors received no specific funding for this study. Dr Tsai acknowledges salary support from the US National Institutes of Health (K23MH096220) and the Robert Wood Johnson Health and Society Scholars Program. Role of the Funder/Sponsor: The funders had no role in the preparation, review, or approval of the manuscript, and the decision to submit the manuscript for publication. 1. Mundt AP, Chow WS, Arduino M, et al. Psychiatric hospital beds and prison populations in South America since 1990: does the Penrose hypothesis apply? JAMA Psych. 2015;72(2):112-118. 2. United Nations Development Programme. Seguridad Ciudadana Con Rostro Humano: Diagnóstico y Propuestas Para América Latina: Informe Regional de Desarrollo Humano 2013-2014. New York, NY: United Nations Development Programme; 2013. 3. Lamb HR. Does deinstitutionalization cause criminalization? the Penrose hypothesis. JAMA Psych. 2015;72(2):105-106. 4. Wooldridge JM. Fixed-effects and related estimators for correlated random-coefficient and treatment-effect panel data models. Rev Econ Stat. 2005;87(2):385-390. doi:10.1162/0034653053970320. 5. Gerry CJ. The journals are full of great studies but can we believe the statistics? revisiting the mass privatisation: mortality debate. Soc Sci Med. 2012; 75(1):14-22.

In Reply We thank Tsai and Venkataramani for their comments, which raise important methodological issues and challenge the findings presented in our article.1 They reconstructed the data set and stated that the association found between psychiatric bed numbers and prison populations disappears once they adjusted for year fixed effects or linear time trends. Yet, they did not use the same data set as in our study. They interpolated the data, ending up with 104 observations, almost twice as many as the 53 observations in our analyis.1 All the additional data points were not observed data but interpolated estimates. This changes the variance and standard errors and leads to completely different results. Computing the analysis with year fixed effects, as suggested by Tsai and Venkataramani, with the real data (available on request), the association between psychiatric bed numbers and prison population rates remains statistically significant (−3.15; 95% CI, −4.72 to −1.60). Adding a linear time trend to the original data set showed a similar result (−2.96; 95% CI, −4.66 to −1.25). We can conclude that the findings presented in our article1 are consistent with the Penrose hypothesis, whether year fixed effects are added or not. The comments of Tsai and Venkataramani point toward a wider methodological issue. If an association between 2 variables tests the hypothesis of a causal relationship, it is paramount to control for potential confounders. One needs to check whether the association is due to a third factor, such as overall time trends whatever such time trends exactly capture (eg, “underlying reasons of crime rates” as suggested by Tsai and Venkataramani).2 In our study, we did not hypothesize any direct causal relationship between bed numbers and prison populations. We just established that there is an association and showed that this is unlikely due to chance. Obviously, there must be reasons for the association and mechanisms behind it. We considered macroeconomic variables, which, however, did not explain the association. Based on different hy-

736

potheses, further factors should be explored in future research. However, adjusting the association for overall time trends without knowing what factors and mechanisms the trends precisely reflect risks eliminating exactly the variance that one is interested in identifying. As acknowledged in our article, the data have limitations —as it often happens in historical data sets—and there were not enough data to perform more reliable tests of associations over time such as cointegration tests.3 Adrian P. Mundt, MD Winnie S. Chow, MSc Stefan Priebe, FRCPsych Author Affiliations: Unit of Social and Community Psychiatry, World Health Organization Collaborating Centre for Mental Health Services Development, Queen Mary University of London, London, England (Mundt, Chow, Priebe); Escuela de Medicina sede Puerto Montt, Universidad San Sebastián, Puerto Montt, Chile (Mundt). Corresponding Author: Adrian P. Mundt, MD, Newham Centre for Mental Health, London E13 8SP, England ([email protected]). Published Online: May 6, 2015. doi:10.1001/jamapsychiatry.2015.0217. Conflict of Interest Disclosures: None reported. Funding/Support: We acknowledge the European Commission Marie Curie International Outgoing Fellowship grant PIOF-2011-INCAS-302346 for funding the study. Role of the Funder/Sponsor: The funders had no role in the preparation, review, or approval of the manuscript, and the decision to submit the manuscript for publication. Correction: This article was corrected online May 21, 2015, for an incorrect date in reference 2. 1. Mundt AP, Chow WS, Arduino M, et al. Psychiatric hospital beds and prison populations in South America since 1990: does the Penrose hypothesis apply? JAMA Psych. 2015;72(2):112-118. 2. Listokin Y. Does more crime mean more prisoners? an instrumental variables approach. 2003. http://digitalcommons.law.yale.edu/fss_papers/564. Accessed January 12, 2015. 3. Ceccherini-Nelli A, Priebe S. Economic factors and psychiatric hospital beds: an analysis of historical trends. Int J Soc Econ. 2007;34(11):788-810.

CORRECTION Error in Figure Caption: In the Original Investigation titled “Mortality in Mental Disorders and Global Disease Burden Implications: A Systematic Review and Metaanalysis ” published online February 11, 2015, and also in the April 2015 print issue of JAMA Psychiatry (doi:10.1001/jamapsychiatry.2014.2502), the caption for the Figure should have read as “MI indicates mental illness.” This article was corrected online. Incorrect Sentences in Abstract: In the Original Article by Rodriguez-Seijas et al titled “Transdiagnostic Factors and Mediation of the Relationship Between Perceived Racial Discrimination and Mental Disorders,” published online April 22, 2015, in JAMA Psychiatry (doi:10.1001/jamapsychiatry.2015.0148), errors occurred in the Abstract. The first sentence of the Abstract’s Design, Setting, and Participants section should read as follows: “Quantitative analysis of 12 common diagnoses that were previously assessed in a nationally representative sample (N = 5191) of African American and Afro-Caribbean adults in the United States, taken from the National Survey of American Life, and used to test the possibility that transdiagnostic factors mediate the effects of discrimination on disorders.” The third sentence of the Abstract’s Design, Setting, and Participants section should read as follows: “Latent variable measurement models, including factor analysis, and indirect effect models were used in the study.” This article was corrected online.

JAMA Psychiatry July 2015 Volume 72, Number 7 (Reprinted)

Copyright 2015 American Medical Association. All rights reserved.

Downloaded From: http://archpsyc.jamanetwork.com/ by a Central Michigan University User on 09/24/2015

jamapsychiatry.com

A More Robust Test of the Penrose Hypothesis.

A More Robust Test of the Penrose Hypothesis. - PDF Download Free
61KB Sizes 3 Downloads 11 Views