Responsiveness and minimal important differences for patient reported outcomes

Abstract

Patient reported outcomes provide the patient's perspective on the effectiveness of treatment. The draft Food and Drug Administration guidance on patient reported outcomes for labeling and promotional claims raises a number of method and measurement issues that require further clarification, including methods of determining responsiveness and minimal important differences. For clinical trials, instruments need to be based on a clear conceptual framework, have evidence supporting content validity and acceptable psychometric qualities. The measures must also have evidence documenting responsiveness and interpretation guidelines (i.e., minimal important difference) to be most useful as effectiveness endpoints in clinical trials. The recommended approach is to estimate the minimal important difference based on several anchor-based methods, with relevant clinical or patient-based indicators, and to examine various distribution-based estimates (i.e., effect size, standardized response mean, standard error of measurement) as supportive information, and then to triangulate on a single value or small range of values for the MID. Confidence in a specific MID value evolves over time and is confirmed by additional research evidence, including clinical trial experience. The MID may vary by population and context, and no one MID will be valid for all study applications involving a PRO instrument. Responsiveness and MID must be demonstrated and documented for the particular study population, and these measurement characteristics are needed for PRO labeling and promotional claims.

The quality of spine surgery from the patient’s perspective: Part 2. Minimal clinically important difference for improvement and deterioration as measured with the Core Outcome Measures Index

“…The MCIDs reported here should be of assistance in planning clinical studies ''nested'' within spine surgery registries (e.g. [11]); however, as highlighted by others [12,18,20,21], it must be borne in mind that the MCID should not be considered as an exact, fixed value, but as an approximate threshold. The MCID can vary depending on the patient group and their initial scores, the treatment under investigation, the method used for its determination, and the choices made in optimizing for sensitivity or specificity [18,20,21].…”

“…[11]); however, as highlighted by others [12,18,20,21], it must be borne in mind that the MCID should not be considered as an exact, fixed value, but as an approximate threshold. The MCID can vary depending on the patient group and their initial scores, the treatment under investigation, the method used for its determination, and the choices made in optimizing for sensitivity or specificity [18,20,21]. The strategies used to assess an instrument's responsiveness always depend on some external criterion for rating ''improvement,'' and to perform ROC analyses this criterion must be dichotomous.…”

Quality of life of adolescents with end-stage renal disease and kidney transplant

“…Statistical power achieved with this small sample size was 75% to detect large differences between groups (i.e. 8 or more points on the CHIP-AE scores) [30,31], with an important decrement in statistical power to detect smaller differences. On the other hand, the high prevalence of kidney transplant recipients reflects the excellent Spanish transplantation framework.…”

A patient-reported outcome instrument to assess the impact of oropharyngeal mucositis on health-related quality of life: a longitudinal psychometric evaluation

“…In this validation study, we focused on responsiveness to changes in clinical status over time using an anchor-based approach [21]. There were statistically significant corresponding changes in scores for the OMQoL subscales among varying levels of changes in WHO OM scores.…”

“…The enrolled subjects were asked to complete the OMQoL and the Chinese version of the EORTC Quality of life Questionnaire-Core 30 [EORTC QLQ-C30 (Ch)] [4] in a random order at baseline and twice a week until 3 weeks completion of stomatotoxic chemotherapy or conditioning regimen for HSCT (D1, 4, 7, 10, 14, 17, 21, 24, and 28), as well as at baseline and then weekly until 3 weeks completion of head/neck irradiation (D1, 7,14,21,28,35,42,49,56,63,70). In each study time point, OM was measured using the WHO Mucositis Grading System [32].…”