Defining ‘Response’ in Antipsychotic Drug Trials: Recommendations for the Use of Scale-Derived Cutoffs

Abstract

Scale-derived cutoff points are frequently used to define 'response' in antipsychotic drug trials. This procedure is useful, because responder rates can be understood more intuitively than a difference in means of rating scales. As various definitions of response have been used, we examined original participant data to assess whether the choice of the Brief Psychiatric Rating Scale-based response cutoff had an impact on the results of seven (n ¼ 1870) antipsychotic drug trials in schizophrenia. We also analyzed whether the chronicity of the illness has an impact on the question of which cutoff is most sensitive in detecting differences between drugs. The results in terms of p-values and response rate differences varied substantially in dependence on the cutoff chosen. The use of response rate ratios attenuated the variability. In contrast to a widely held belief, low response cutoffs were not more sensitive in detecting differences between drugs than higher cutoffs. In more chronic, less responsive participants, there was a trend for higher cutoffs to be less sensitive in detecting differences between drugs than lower ones. The results of clinical trials depend considerably on the response cutoff chosen. Therefore, the cutoff should never be chosen post hoc, a large range of cutoffs should be presented and the a priori choice of the primary cutoff should be based on clinical relevance. The use of ratios rather than differences attenuates the variability. Cutoffs need to be calculated on the basis of 0-6 rather than on 1-7 scoring systems. We suggest a table presenting responder rates in 25 percent steps covering the whole range up to 100% reduction from baseline, which could be displayed together with recently presented criteria for remission.

Cognitive therapy for people with schizophrenia spectrum disorders not taking antipsychotic drugs: a single-blind randomised controlled trial

“…observed cases) achieving a 25%, 50%, 75% and 100% improvement/deterioration on adjusted PANSS total scores 32 at both 9 months and 18 months (Table 4), as has been recommended for trials using the PANSS 33 . Examining the proportion of participants achieving good clinical outcomes in each condition (defined using an improvement of >50% in adjusted PANSS total scores), we found that, at 9 months 7/22 from CT (31.8%) and 3/23 from TAU (13.0%) had achieved good clinical outcomes, and at 18 months 7/17 from CT (41.2%) and 3/17 from TAU (17.6%) had achieved good clinical outcomes.…”

Augmentation of Antipsychotics with Electroconvulsive Therapy in Treatment-Resistant Schizophrenia Patients with Dominant Negative Symptoms: A Pilot Study of Effectiveness

“…The percentage change of scores was calculated according to Leucht et al [15], based on the principle that a patient with no psychopathological symptoms scores 1 in all PANSS scale items. The formula for calculating change was as follows: [(P t2 - N) - (P t1 - N)/(P t1 - N)]·100, where P t1 is the PANSS subscale score at the beginning of the study, P t2 is that at the end of the study and N = the number of PANSS subscale items.…”

Remisión sintomática y recuperación funcional en pacientes que padecen esquizofrenia

“…8,[44][45][46] La "respuesta al tratamiento" ha sido definida como "una mejoría significativa en la psicopatología del paciente, a pesar de que aún esté sintomático al final del tratamiento". 43 Para medir la respuesta al tratamiento, pueden ser considerados una gran variedad de puntos de corte: 20%, 30%, 40% o 50%, utilizando las medias al inicio y al final del tratamiento para calcular el porcentaje de la reducción de los síntomas.…”

“…El uso de esta fórmula ha sido recomendado para clínicos e investigadores que estén tratando a pacientes con esquizofrenia. 43,45 Debido a la gran cantidad de estudios encontrados, en el cuadro 2 se presenta un resumen de las principales investigaciones sobre remisión sintomática. De acuerdo a diversas revisiones recientes, los porcentajes de remisión se ubican entre: 20-60%; 39 30-70%; 48 17-88%.…”