Summary Background In the phase 3 CheckMate 025 study, previously treated patients with advanced renal cell carcinoma (aRCC) randomised to nivolumab had an overall survival (OS) benefit versus everolimus. We compared health-related quality of life (HRQoL) between treatment arms and explored the relationship with OS. Methods In this open-label study (NCT01668784) in 146 oncology centres in 24 countries, patients with aRCC were randomised (1:1; block size of 4) to receive nivolumab 3 mg/kg by 60-minute intravenous infusion every 2 weeks or everolimus 10 mg tablet orally once daily. The study was stopped early at the planned interim analysis in July 2015 as the study met its primary endpoint. A protocol amendment permitted patients in the everolimus group to cross over to nivolumab treatment. All patients not on active study therapy are being followed for survival. At the interim analysis, HRQoL was assessed using the Functional Assessment of Cancer Therapy–Kidney Symptom Index–Disease Related Symptoms (FKSI-DRS) and European Quality of Life (EuroQol)-5 Dimensions (EQ-5D) questionnaires. FKSI-DRS completion rate was calculated using number of patients with at least one baseline assessment and at least one post-baseline assessment. FKSI-DRS completion was defined as completion of five or more items; otherwise data were treated as missing. FKSI-DRS symptom index score was prorated for missing items. No adjustments were made for EQ-5D missing data. Descriptive statistics and multivariate analyses, including mixed-effects model repeated-measures (MMRM) were used. Analyses were powered according to the original study protocol. A correlation between baseline HRQoL and OS was performed. Findings Patients were randomised from October 2012 through March 2014. HRQoL data were collected at baseline for 362 (88%) of 410 (nivolumab) and 344 (84%) of 411 (everolimus) randomised patients. The mean difference (95% CI) in FKSI-DRS score between nivolumab and everolimus arms was 1·6 (1·4–1·9, p<0·001) with descriptive statistics and 1·7 (1·2–2·1, p<0·001) with MMRM analysis. More patients experienced clinically meaningful HRQoL improvement with nivolumab versus everolimus (200 [55%] of 361 vs 126 [37%] of 343, respectively; p<0·001). Median (95% CI) time to improvement in HRQoL was shorter in patients treated with nivolumab (4·7 [3·7–7·5] months) versus everolimus (not reached [range not estimable]). A positive correlation between OS and FKSI-DRS (r=0·27; p≤0·001), EQ-5D utility (r=0·24, p≤0·001), and EQ-5D VAS (r=0·26, p≤0·001) baseline scores across both arms was observed. Interpretation Nivolumab treatment was associated with HRQoL improvement compared with everolimus in previously treated patients with aRCC. Funding Bristol-Myers Squibb. Dr. Motzer received support through the NIH/NCI Cancer Center Support Grant P30 CA008748.

DEEDevelopmental and epileptic encephalopathy HRQoLHealth-related quality of life AIM To assess the relevance and generalizability across countries of concepts of the impact of Dravet syndrome beyond seizures, as recognized by families.

these studies, 26 used proportion of days covered, 23 used medication possession ratio, and 72 used self-reported questionnaires (e.g., the Morisky Scale) to assess MMA. About 50% of the studies included more than one method for measuring MMA, and different variations of medication possession ratio and proportion of days covered were used for measuring MMA. Conclusions: There appears to be no standardized method to measure MMA. With an increasing prevalence of polypharmacy, more efforts should be directed toward constructing robust measures suitable to evaluate adherence to complex regimens. Future research to understand the validity and reliability of MMA measures and their effects on objective clinical outcomes is also needed.

This study showed the wider potential impact of DS to extend beyond that of seizures, demonstrating that there is a need for additional patient- and caregiver-relevant concepts to be measured in clinical trials to fully identify the value of therapeutic interventions.

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IntroductionTuberculosis (TB) is a leading cause of morbidity and mortality in South Africa. Clinical parameters are important objective outcomes in TB; however they often are not directly correlated with subjective well-being of the patient, but can be assessed using patient-reported outcome (PRO) measures. Health-related quality of life (HRQOL) is a specific PRO generally multi-dimensional in nature and includes physical, mental and social health domains. The inclusion of HRQOL PROs in trials and clinical practice can provide additional information beyondclinical and microbiological parameters. Furthermore, HRQOL may be associated with medication adherence. This review focuses on patient-reported HRQOL and its association with medication adherence in TB patients in South Africa.MethodsA comprehensive search strategy was developed focusing on the impact of TB on patient-reported HRQOL,the existence of a conceptual framework of TB-specific HRQOL, determinants of medication adherence and the association of HRQOL with medication adherence. Data were extracted from all identified articles and additionaldata extraction was performed by two independent reviewers with special focus on longitudinal studies in order to understand changes of HRQOL and adherence over time. Research gaps were identified with regard to patient-reported HRQOL and medication adherence.ResultsA total of 66 articles met the eligibility criteria. Ten HRQOL studies and one adherence study used a longitudinal design, none of these in South Africa. A variety of different generic and disease-specific HRQOL measures were identified in the articles. In South Africa four HRQOL and five adherence studies (non-longitudinal) were published. Similar factors (socio-demographic, socio-economic, disease-related, therapy-related and psycho-social aspects) affect HRQOL and adherence. Although standard TB treatment improved all health domains, psychological well-being and social functioning remained impaired in microbiologically cured patients after treatment.ConclusionWhile evidence of TB impact on HRQOL and medication adherence and their association exists, it is verylimited for the South African situation. No valid and reliable TB-specific HRQOL measures were identified in this systematicreview. An assessment of HRQOL in TB patients in South Africa is required as this may assist with improving current disease management programmes, medication adherence and national treatment guidelines.Electronic supplementary materialThe online version of this article (doi:10.1186/s12955-016-0442-6) contains supplementary material, which is available to authorized users.

BackgroundThe evaluation of patient-reported health-related quality of life (HRQOL) in pulmonary tuberculosis (TB) contributes to a comprehensive understanding of the burden associated with this disease. The aim of this study was to assess the overall impact of TB on the health status and on single health domains identified in the WHO definition of health, including physical, mental and social health aspects.MethodsFour instruments for HRQOL evaluation were applied in a longitudinal multicentre study during six-month standard TB treatment in South Africa. These included the generic SF-12 and EQ-5D-5L, the disease-specific St. George´s Respiratory Questionnaire (SGRQ) and the condition-specific Hospital Anxiety and Depression Scale (HADS). Statistical analysis included significance testing, univariable and multivariable analysis, and repeated measures ANOVA. Change over time in the physical component score (PCS) of SF-12 was defined as primary endpoint. A target sample size of 96 patients was estimated.ResultsHRQOL of the study participants was impaired in all physical, mental and psycho-social health domains at treatment start. HRQOL improved significantly and in a clinically meaningful manner during the course of standard TB treatment, over the period of the study. The greatest improvement (95%) was observed in mental health. Younger patients with higher education and who were employed had a better HRQOL.DiscussionThis study demonstrates the need for an integrative understanding of TB with HRQOL as core element to inform gaps in current TB management. Improvements in the management of TB following an integrative patient-centred approach will contribute towards meeting the United Nations Sustainable Development Goal 3 (SDG3) target and will support the End TB strategy of the WHO.

The transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) evolves over time and it can be challenging for physicians to identify progression early. Typically, SPMS is diagnosed retrospectively with a significant delay, based on a history of gradual worsening, independent of relapses, following an initial relapsing-remitting disease course. As such, SPMS is often associated with a considerable period of diagnostic uncertainty. This study aimed to explore and characterize key symptoms and impacts associated with transitioning from RRMS to SPMS and inform the content for a tool to support evaluation of early subtle signs suggestive of progressive disease. Methods: The qualitative study involved 60-min, face-to-face, concept elicitation (CE) interviews with 32 patients with MS (US = 16 and Germany = 16); and 30-min, telephone, CE interviews with 16 neurologists (US = 8 and Germany = 8). Multivariate analysis on data from a real-world observational study of 3294 MS patients assessed the differences between early-RRMS and early-SPMS, and identified factors that were significant drivers of this difference. These studies informed selection of the key variables to be included in a pilot tool. Sixteen physicians used the pilot tool, presented as a paper questionnaire, with a sample of patients whom they suspected were progressing to SPMS (n ≥ 5). Following this, the physicians participated in a 30-min cognitive debriefing (CD) interview to evaluate the relevance and usefulness of the tool. Qualitative analysis of all anonymized, verbatim transcripts was performed using thematic analysis. Results: Patients and physicians reported signs that indicated progression to SPMS including gradual worsening of symptoms, lack of clear recovery, increased severity and presence of new symptoms. No specific symptoms definitively indicated progression to SPMS, however a number of potential symptoms associated with progression were identified by SPMS patients and physicians, including worsening ambulation, cognition, balance, muscle weakness, visual symptoms, bladder symptoms and fatigue. Quality of life domains reported to be more severely impacted in SPMS than MS in general included: physical activity, work, daily activities, emotional and social functioning. Multivariate analysis of the observational study data identified several variables strongly associated with progression to SPMS including, requirement of assistance in daily living, presence of motor symptoms, presence of ataxia/coordination symptoms, and unemployment. Physicians reported that items included in the tool were easy to understand and relevant. Physicians also reported that there is an unmet need for a tool to help identify signs of SPMS progression and so the tool would be useful in clinical practice. Conclusions: This was the first stage of development of a novel, validated, physician-completed tool to support