Abstract
Purpose
To quantify clinical trial participants’ and investigators’ judgments with respect to the relative importance of efficacy and safety attributes of antipsychotic treatments for schizophrenia, and to assess the impact of formulation and adherence.
Methods
Discrete-choice experiment surveys were completed by patients with schizophrenia and physician investigators participating in two phase-3 clinical trials of paliperidone palmitate 3-month long-acting injectable (LAI) antipsychotic. Respondents were asked to choose between hypothetical antipsychotic profiles defined by efficacy, safety, and mode of administration. Data were analyzed using random-parameters logit and probit models.
Results
Patients (N=214) and physicians (N=438) preferred complete improvement in positive symptoms (severe to none) as the most important attribute, compared with improvement in any other attribute studied. Both respondents preferred 3-month and 1-month injectables to oral formulation (P<0.05), irrespective of prior adherence to oral antipsychotic treatment, with physicians showing greater preference for a 3-month over a 1-month LAI for nonadherent patients. Physicians were willing to accept treatments with reduced efficacy for patients with prior poor adherence. The maximum decrease in efficacy (95% confidence interval [CI]) that physicians would accept for switching a patient from daily oral to 3-month injectable was as follows: adherent: 9.8% (95% CI: 7.2–12.4), 20% nonadherent: 25.4% (95% CI: 21.0–29.9), and 50% nonadherent: >30%. For patients, adherent: 10.1% (95% CI: 6.1–14.1), nonadherent: the change in efficacy studied was regarded as unimportant.
Conclusion
Improvement in positive symptoms was the most important attribute. Patients and physicians preferred LAIs over oral antipsychotics, with physicians showing a greater preference for 3-month over 1-month LAI. Physicians and patients were willing to accept reduced efficacy in exchange for switching a patient from an oral formulation to a LAI.
Supplementary materials
Figure S1 Example of physician discrete-choice question (first set).
Abbreviation: EPS, extrapyramidal symptoms.
Figure S2 Example of patient (female) discrete-choice question (first set).
Abbreviation: Pat, patient.
Figure S3 Example of patient (male) discrete-choice question (first set).
Abbreviation: Pat, patient.
Figure S4 Example of physician formulation question with follow-up adherence information (second set).
Abbreviation: EPS, extrapyramidal symptoms.
Figure S5 Example of patient formulation question with follow-up adherence information (second set).
Notes: Medicines are the same except as shown in the figure. Pat typically never misses taking her medicine.
Abbreviation: Pat, patient.
Acknowledgments
The authors acknowledge Vaibhav Deshpande (SIRO Clinpharm Pvt. Ltd.) for writing support, Ashwini Patil, ISMPP CMPP™ (SIRO Clinpharm Pvt. Ltd., Thane, Maharashtra, India) for assistance with revisions and editorial support, and Ellen Baum (Janssen Research & Development, LLC, Raritan, NJ, USA) for additional editorial support for the development of this manuscript. Janssen Research & Development, LLC provided funding to RTI Health Solutions to conduct this study.
Author contributions
Drs Katz, Levitan, Gopal, Fairchild, Hauber, Pugh, and Weinstein contributed to the design of this study, data analysis, interpretation, and authorship. All authors met ICMJE criteria and all those who fulfilled those criteria are listed as authors. All authors had access to the study data, provided direction and comments on the manuscript, had final approval of the document, and made the final decision about where to publish these data.
Disclosure
Drs Katz, Gopal, Levitan, and Weinstein are employees of Janssen and hold company stocks. Dr Levitan is also a stockholder in Baxter International, Inc., Pharmaceutical Holdrs Trust, and Zimmer Holdings, Inc. He also owns stock in a variety of companies that at times include pharmaceutical and health care–related companies. Dr Hauber is an employee of RTI Health Solutions. Drs Pugh and Fairchild were employees of RTI Health Solutions at the time this study was conducted. The authors report no other conflicts of interest in this work.