Volume 321, March 2023, 115071Author links open overlay panelAbstract

Multi-site randomized effectiveness trials evaluate treatments under real-world conditions. Whether results change practice is under-studied. A 6-month 26-site Veterans Health Administration (VHA) cooperative study published in 2011 compared an oral second-generation antipsychotic, risperidone, to placebo for refractory PTSD with null results. National VHA administrative data compared new starts on risperidone during the 5 years before and after the year of publication. Among the 450,000–841,000 Veterans diagnosed with PTSD annually from 2006 to 2016 the proportion with new starts on risperidone declined every year before and after publication. No evidence of an effect of null study results on VHA clinical practice was observed.

Section snippetsBackground

It has long been recognized that short-term placebo-controlled randomized clinical trials (RCTs), used for Food and Drug Administration (FDA) marketing approval, are not adequate for determining whether the longer term effectiveness and safety of such medications merit system-wide replacement of older, often less expensive, drugs currently in use (Tunis et al., 2003). Randomized comparative effectiveness trials compare new drugs to placebo or widely used comparators at multiple sites, under

Design and sample

Data used for the present longitudinal observational analysis were derived from the national VHA electronic health records available from the VA Corporate Data Warehouse, which document clinical diagnoses and VA prescription fills for all Veterans treated by VHA.

The study sample included all VHA patients who received an ICD-9 diagnosis of PTSD (ICD-9 code 309.81) from an inpatient or outpatient clinical encounter in the years 2006–2016. Veterans were represented as unique observations for each

Results

The number of Veterans diagnosed with PTSD increased steadily from 450,000 in 2006 to 841,000 in 2016 while the proportion of Veterans diagnosed with PTSD who received new, first-time, prescriptions for risperidone decreased steadily before and after publication of CSP#504 as did new starts on other SGAs (Fig. 1).

Statistical analyses showed that there were a significantly greater proportion of new starts on Long-Acting Injectable (LAI) risperidone from 2006 to 2009 than in 2011 (Supplemental

Discussion

As hypothesized, new starts on oral risperidone for Veterans diagnosed with refractory PTSD in VHA declined following the publication of a multisite randomized clinical trial of this treatment with null results, thus failing to provide justification for its continued use. However, examination of data from the years prior to publication of CSP#504 showed the decline in new starts of LAI risperidone preceded publication and thus could not be attributed to the study. A similar pattern was found

Ethics approval and consent to participate

The study was approved with a waiver of informed consent by the Boston VA IRB.

Consent for publication

All of the authors approved the final version of this article for publication.

Availability of data and materials

Veterans Health Administration data used for these analyses are not available to the public.

Authors' contributions

RR wrote the initial draft, based on analyses by SK. The text was edited with added contributions by SA, CH, and RF and substantive input from JP, DS, and RS. All of the authors approved the final version of this article.

CRediT authorship contribution statement

Robert Rosenheck: Conceptualization, Methodology, Data curation, Writing – original draft. Stephen G. Kurtz: Conceptualization, Methodology. Sonia T. Anand: Conceptualization, Methodology. Cynthia Hau: Conceptualization, Methodology. Diane Smedberg: . Rosmery Sicilia: Supervision. James F. Pontzer: Conceptualization, Methodology. Ryan E. Ferguson: Supervision.

Declaration of Competing Interest

None of the authors have any conflicts of interest or competing interests to report.

Acknowledgements

None.

Funding

The study was funded by the VA Cooperative Studies Program which also funded with original study which also received medication and modest support from Janssen Pharmaceuticals. Funding organization had no role in the. writing or editing of the manuscript.

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