Physician and patient benefit-risk preferences from two randomized long-acting injectable antipsychotic trials

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.

Keywords: benefit–risk assessment; long-acting injectable; patient preference; physician preference; schizophrenia; survey.

Figure 1

Preference weights for first series of choice questions for physicians. Notes: Each bar represents the improvement in utility associated with switching from the least preferred to the most preferred level of each attribute. The vertical bars surrounding each mean preference weight denote the 95% CI about the point estimate. Abbreviations: CI, confidence interval; EPS, extrapyramidal symptoms; N, number of respondents who answered the question.

Figure 2

Preference weights for first series of choice questions for patients. Notes: ^aUnusual beliefs, hearing voices, and not trusting people to no unusual beliefs; ^bdifficulty in speaking with others or showing emotions to speaks normally and has emotions; ^cdecreased interest in social activities to less interest in social activities. Each bar represents the improvement in utility associated with switching from the least preferred to the most preferred level of each attribute. The vertical bars surrounding each mean preference weight denote the 95% CI about the point estimate. Abbreviations: CI, confidence interval; EPS, extrapyramidal symptoms; N, number of respondents who answered the question.

Figure 3

Relative importance assigned by physicians in second series of choice questions. Note: The vertical bars surrounding each mean preference weight denote the 95% CI about the point estimate. Abbreviations: CI, confidence interval; EPS, extrapyramidal symptoms; N, number of respondents who answered the question.

Figure 4

Relative importance assigned by patients to second series of choice questions. Notes: A line plot is used here, rather than a bar plot, since the preference changes are not monotonic and cannot be represented by single bars. The vertical bars surrounding each mean preference weight denote the 95% CI about the point estimate. Abbreviations: CI, confidence interval; N, number of respondents who answered the question.