How to address the challenges of evaluating treatment benefits-risks in rare diseases? A convergent mixed methods approach applied within a Merkel cell carcinoma phase 2 clinical trial

Abstract

BackgroundDemonstrating treatment benefits within clinical trials in the context of rare diseases is often methodologically and practically challenging. Mixed methods research offers an approach to overcome these challenges by combining quantitative and qualitative data, thus providing a better understanding of the research question. A convergent mixed methods design in the context of Merkel cell carcinoma, a rare skin cancer, was used during the JAVELIN Merkel 200 trial (NCT02155647).MethodsNine patients receiving avelumab in the JAVELIN Merkel 200 trial were interviewed at baseline prior to receiving study treatment, and at 13 weeks and 25 weeks after first avelumab administration. Key concepts of interest identified from the baseline interviews were physical functioning, fatigue/energy, and pain. Patient perceptions of the overall change in their cancer-related health status since starting study treatment were also recorded. During qualitative analysis, at each time-point, each concept of interest was assigned a category describing the trend in change (e.g. newly emerged, no change/stable, improved, worsened, ceased/disappeared). In parallel, patients’ tumour status was determined by the clinical overall response status as per the clinical trial protocol.ResultsA high concordance between patient-reported qualitative data and assessed tumour response was observed. All eight patients who clinically improved had perceived a subjective improvement in their disease since the beginning of the study; the single patient whose disease worsened had a perceived deterioration. Patient perceived benefit in physical functioning, fatigue/energy and pain was subsequent to the measured change in clinical status as assessed by tumour response. This suggests that patient-reported assessment should be examined over the long term in order to optimally capture meaningful treatment effect.ConclusionEmbedding qualitative research in clinical trials to complement the quantitative data is an innovative approach to characterise meaningful treatment effect. This application of mixed methods research has the potential to overcome the hurdles associated with clinical outcomes assessment in rare diseases.

Patient Experiences with Avelumab in Treatment-Naïve Metastatic Merkel Cell Carcinoma: Longitudinal Qualitative Interview Findings from JAVELIN Merkel 200, a Registrational Clinical Trial

“…This study in patient with treatment-naïve mMCC should be considered as complementary to the previously published study among chemotherapy refractory patients with mMCC [17][18][19].…”

“…The present article reports the findings from the qualitative interviews conducted with a large international sample of treatment-naïve patients with mMCC receiving avelumab as first-line treatment and aims to complement previous findings in patients with mMCC receiving avelumab as secondor later-line treatment [17][18][19].…”

“…Data from the collected qualitative interviews alongside the trial were used to support its psychometric validation [34]. A mixed-method research approach using the qualitative interview data together with the questionnaire quantitative data and clinical data to provide a wholistic perspective on patient experience has been previously published using part A data [17]. Potential future work using this part B data could be conducted applying such a mixed-method research approach to triangulate qualitative findings and quantitative findings and draw further insights on patient experience with avelumab.…”

“…Findings from interviews conducted with patients with mMCC receiving avelumab as second-or laterline treatment (part A) have previously been reported [17][18][19]. Briefly, those patients, mostly from the USA, described MCC as painless and symptomless.…”

Comparing Physician and Patient Perspectives on Prophylactic Treatment with BAY 94-9027 for Severe Haemophilia A: A Post Hoc Analysis

“…The absence of improvement in the Haemo-QoL-A between the two assessments could have been the result of high scores at baseline, limiting the ability to capture significant improvement. This study emphasizes the added value of physician and patient interviews in clinical trials, in particular in rare diseases, to complement patient-reported outcome or clinical quantitative data and to gain additional insight into trial data, support interpretation of other quantitative assessments and endpoints to discuss meaningfulness of change [21][22][23][24].…”