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

Abstract

PurposeTo 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.MethodsDiscrete-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.ResultsPatients (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.ConclusionImprovement 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.

Quantifying the treatment goals of people recently diagnosed with schizophrenia using best&ndash;worst scaling

“…The finding in this study that reduced disease symptoms and functional impacts were most important, whereas reduced risk of treatment side effects, specifically weight gain, sexual problems, fatigue, and restlessness, were least important, is consistent with that from a previous stated preference survey in an older group of individuals with schizophrenia (mean age =41 years) that used a discrete choice experiment (DCE) methodology. 35 In addition, consistent with the finding in this study that people with LAI experience more often preferred LAI over oral medication, the patients in the DCE study, who were participants in a LAI trial, had a higher preference for a LAI over oral medication. 35 Another study, involving qualitative interviews, also found that preference was higher for LAI among those with LAI experience.…”

Role of 3-monthly long-acting injectable paliperidone in the maintenance of schizophrenia

“… 60 The second RCT aimed to demonstrate non-inferiority of PP3M compared with PP1M in terms of relapse rates, changes in Positive and Negative Syndrome Scale (PANSS) scores, Clinical Global Impression-Severity (CGI-S) score and Personal and Social Performance (PSP) score. 61 Savitz et al, 62 Katz et al, 63 Chirila et al, 64 and Gopal et al 65 studied outcome measures within the samples or sub-samples of the 2 previously described RCTs. In details, Savitz et al 62 analyzed data derived from the previously mentioned non-inferiority RCT comparing PP3M with PP1M treatment; to investigate symptomatic and functional remission in the DB phase of this RCT, Katz et al 63 investigated native English-speaking trial participants’ and English-speaking investigators’ judgments about paliperidone formulations and adherence; Chirila et al 64 compared occupational status and health care resource use between treatment groups (PP3M vs placebo and PP3M vs PP1M), using data from the whole samples of the 2 RCTs and Gopal et al 65 evaluated caregiver burden in the 2 RCTs.…”

“… 61 Savitz et al, 62 Katz et al, 63 Chirila et al, 64 and Gopal et al 65 studied outcome measures within the samples or sub-samples of the 2 previously described RCTs. In details, Savitz et al 62 analyzed data derived from the previously mentioned non-inferiority RCT comparing PP3M with PP1M treatment; to investigate symptomatic and functional remission in the DB phase of this RCT, Katz et al 63 investigated native English-speaking trial participants’ and English-speaking investigators’ judgments about paliperidone formulations and adherence; Chirila et al 64 compared occupational status and health care resource use between treatment groups (PP3M vs placebo and PP3M vs PP1M), using data from the whole samples of the 2 RCTs and Gopal et al 65 evaluated caregiver burden in the 2 RCTs. Weiden et al 66 made a post-hoc analysis comparing median time to relapse across the treatment withdrawal arms of 3 different RCTs (Kramer et al, 67 Hough et al, 68 and Berwaerts et al 60 ), which compares the 3 formulations of paliperidone with placebo.…”

“…Katz et al 63 analyzed preferences between oral antipsychotic treatments, PP1M and PP3M with a survey performed by English native speaking and English-speaking physicians who participated in the 2 RCTs 60 , 61 as previously described.…”

“I live, I don't work, but I live a very normal life”—A qualitative interview study of Scandinavian user experiences of schizophrenia, antipsychotic medication, and personal recovery processes

“…An American study has surveyed doctors and service users by asking them to rate the importance of efficacy, safety, and formulation for monthly, 3‐monthly, or oral administration. Both doctors and service users pointed toward the reduction of positive symptoms as the most important target, and both groups preferred LAIs over oral treatment . An Australian study has rated patient satisfaction with PP3M among service users as well as psychiatrists based on questionnaires.…”