HAS MY PATIENT RESPONDED TO TREATMENT? THE SELDOM ASKED QUESTION IN PERSONALIZED MEDICINE RESEARCH

Purpose:  

   Symptom report scales are still widely used in psychiatry to assess whether an individual patient has responded to treatment.  The minimum clinically important difference (MCID) is a benchmark used to design adequately powered trials that can capture clinically important changes in patient outcomes.  However, the MCID is a group average, its use for judging an individual patient response must be qualified.  A consensus has emerged that a larger MCID is appropriate for individual patients to account for the greater level of uncertainty.  However, we don’t know whether clinicians, either implicitly or explicitly, use a larger MCID when they are assessing an individual patient’s response to treatment, or whether knowledge of the patient’s “responsiveness” genotype affects this judgement (reflecting the notion of genetic exceptionalism).

Method:  

   We developed a series of twenty six patient vignettes illustrating two treatments showing an individual patient’s pre and post treatment score on a widely used symptom report scale within psychiatry.  This Positive Symptoms Subscale of the “PANSS” assessment tool is widely used in the management of major psychosis, in parallel group treatment trials an MCID of 15 points is commonly employed. Each vignette specified whether or not the patient had a genetic biomarker which indicated that they possessed a “hyper responsiveness” trait for the treatment.  In judging the vignettes, psychiatrists (n=53) decided whether they considered that the patient had responded to treatment.  Participants were also informed about the side effects of the treatment, and had to decide upon which of two treatments they would recommend.

Result:   

   On average, psychiatrists accepted an average change score of 11 before consistently classifying a patient as “responder” to treatment, i.e. a change score that is less than the group average MCID indicating that they were underestimating the imprecision in an individual’s response.  Thus clinicians are at risk of classifying patients as responders when this may not be the case, perhaps unnecessarily prolonging the exposure to treatment side effects.  The presence of the “hyper-responsiveness” genotype made no difference to the change score required before classifying a patient as a “responder” to treatment.  

Conclusion:   

   Our results have implications for the practice of stratified medicine and psychiatrists should be made aware that a larger MCID should be used when assessing an individual patient’s response to treatment.