Paving the way for patient centricity in real-world evidence (RWE): Qualitative interviews to identify considerations for wider implementation of patient-reported outcomes in RWE generation.

Objectives: Real-world evidence (RWE) generation can be enhanced by including patient-reported outcomes (PROs). Methods for collecting and using PRO data in the real-world setting are currently underdeveloped and there is no international guidance specific to its use in this context. This study explored stakeholders' perspectives and needs for using PROs in RWE generation. Barriers, facilitators, and opportunities for wider use of PROs in real-world studies were also investigated. Methods: Online semi-structured interviews were conducted with international stakeholders: patients, patient advocates, regulators, payers, clinicians, academic researchers, and industry experts. Interviews were recorded, transcribed verbatim and analysed using NVivo 20. Thematic analysis was conducted based on the updated Consolidated Framework for Implementation Research (CFIR). Results: Twenty-three interviews were conducted. Participants confirmed that the use of PROs in RWE generation is not yet well established. Participants expressed a mixed level of confidence in the value of PROs collected in a real-world setting. Operational challenges associated with collecting routine PRO data to inform care delivery at the individual level (e.g., setting up infrastructure) need to be addressed. Methodological and other challenges (e.g., financing research) associated with collecting prospective de novo data in a real-world setting should be considered to facilitate PRO utilisation in real-world studies. Conclusions: Several opportunities and challenges were identified regarding the broader use of PROs in RWE research. Joint efforts from different stakeholders are needed to maximise PRO implementation, with consideration given to each stakeholders' specific needs (e.g., by developing good practices).

Survival after acute episodes of immune-mediated thrombotic thrombocytopenic purpura (iTTP) - cognitive functioning and health-related quality of life impact: a descriptive cross-sectional survey of adults living with iTTP in the United Kingdom.

OBJECTIVES: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare life-threatening thrombotic microangiopathy affecting adults with unpredictable disease onset and acute presentation. This study aimed to describe the health-related quality of life (HRQoL), cognitive functioning and work productivity of survivors following acute episode(s) of iTTP in the United Kingdom (UK). METHODS: An online survey was developed in collaboration with the TTP Network. Descriptive statistics were calculated for the health questionnaire Short Form Survey-36 Version 2 (SF-36v2), the Hospital Anxiety and Depression Score (HADS), the PROMIS Cognitive Function Abilities Subset - Short Form 6a (PROMIS CFAS - SF6a), and the Work Productivity and Activity Index: Specific Health Problem (WPAI-SHP), along with several iTTP-specific bespoke questions. RESULTS: Fifty participants were recruited between July-November 2019. The mean (standard deviation [SD]) standardized SF-36v2 physical and mental component scores were 42.16 (9.59) and 33.61 (12.34), lower than population norms. The mean (SD) standardized PROMIS CFAS - SF6a score was 39.69 (7.86), lower than population norms. HADS mean (SD) scores of 12.18 (3.14) and 11.78 (2.36) indicated moderate levels of anxiety and depression, respectively. Of those employed (58%), approximately 42.73% of participants reported work productivity loss due to their iTTP. Participants also reported experiencing flashbacks, fatigue interference in family, social and intimate life, and fears of relapse. DISCUSSION AND CONCLUSION: Regardless of recency of the last acute episode, participant scores signified impairments in all domains. Remission from an acute episode of disease does not signify the conclusion of care, but rather the requirement for long-term healthcare particularly focused on psychological support.

Validation of the German version of the Family Reported Outcome Measure (FROM-16) to assess the impact of disease on the partner or family member.

BACKGROUND: The Family Reported Outcome Measure (FROM-16) assesses the impact of a patient's chronic illness on the quality of life (QoL) of the patient's partner or family members. The aim of the study was to translate, explore the structure of and validate the FROM-16. METHODS: The questionnaire was translated from English into German (forward, backward, four independent translators). Six interviews with family members were conducted to confirm the questionnaire for linguistic, conceptual, semantic and experiential equivalence and its practicability. The final German translation was tested for internal consistency, reproducibility and test validity. Criterion validity was tested by correlating the scores of the FROM-16 and the Global Health Scale (GHS). Principal component analysis, factor analysis, and confirmatory factor analysis was used to assess the questionnaire's structure and its domains. Reliability and reproducibility were tested computing the intraclass correlation coefficient (ICC) using one sample t-test for testing the hypothesis that the difference between the scores was not different from zero. RESULTS: Overall, 83 family members (61% female, median age: 61 years) completed the questionnaire at two different times (mean interval: 22 days). Internal consistency was good for the FROM-16 scores (Cronbach's α for total score = 0.86). In those with stable GHS, the ICC for the total score was 0.87 and the difference was not different from zero (p = 0.262) indicating reproducible results. A bi-factor model with a general factor including all items, and two sub-factors comprising the items from the original 2-factor construct had the best fit. CONCLUSIONS: The German FROM-16 has good reliability, test validity and practicability. It can be considered as an appropriate and generic tool to measure QoL of a patient's partner or family member. Due to the presence of several cross-loadings we do not recommend the reporting of the scores of the two domains proposed for the original version of FROM-16 when using the German version. Thus, in reporting the results emphasis should be put on the total score. TRIAL REGISTRATION: Retrospectively registered: DRKS00021070.

Health-related quality of life and work productivity in UK patients with HER2-positive breast cancer: a cross-sectional study evaluating the relationships between disease and treatment stage.

BACKGROUND: The impact of different disease stages and treatment for human epidermal growth factor 2 positive (HER2-positive) breast cancer (BC) on work productivity and health-related quality of life (HRQoL) is poorly understood. METHODS: This was a UK cross-sectional study of 299 adult patients with HER2-positive early or metastatic BC (NCT03099200). Productivity was assessed using the work productivity and activity impairment scale; HRQoL was measured using EuroQol-5 Dimensions-5 levels (EQ-5D-5L), and Functional Assessment of Cancer Therapy Breast (FACT-G and -B) instruments. Three balanced patient groups were recruited: (1) early BC on treatment post-surgery, (2) early BC after completion of adjuvant treatment, (3) during metastatic BC treatment. Between-group comparisons were performed using an analysis of variance. RESULTS: Group 1 comprised 89 patients, Group 2, 108 and Group 3, 102. Age, ethnicity and comorbidities were similar across groups. Patients in Group 3 reported more often being unable to work (significant Bonferroni adjusted p < 0.003). Proportions of employed patients were 50.6%, 50.9% and 27.5% in Groups 1, 2 and 3, respectively. For patients in part-time employment, the number of hours worked was significantly higher in Group 2 patients versus Group 3 (p = 0.002). Group 2 also had significantly lower levels of work absenteeism and overall work impairment compared with Group 1 (p < 0.001). Patients in Group 3 reported worse health utility scores (p ≤ 0.002), moderate or worse problems in the EQ-5D-5L self-care and usual activity domains (p ≤ 0.001), and lower HRQoL as assessed by FACT summary scores (p < 0.001 for FACT-B and -G) than Groups 1 and 2. Poorer HRQoL was significantly associated with higher work impairment (p < 0.001), with the strongest relationships being observed between activity impairment and HRQoL (Pearson's r: 0.67). CONCLUSIONS: Metastatic disease and treatment of HER2-positive BC adversely impacted on work productivity and HRQoL. The results of this study support the idea that being able to delay or prevent the metastatic recurrence of BC, for example by extending the time patients are in remission or at early stage of BC, has wider benefits in terms of patient productivity and HRQoL.

Evaluating patient preference and satisfaction for human immunodeficiency virus therapy in France.

OBJECTIVES: The objectives were 1) to elicit relative preferences for attributes of antiretroviral therapies (ART) in people living with HIV (PLWH) and 2) to explore satisfaction and adherence with current ART. PATIENTS AND METHODS: We conducted a multicenter cross-sectional study, consecutively enrolling PLWH receiving an ART. The quantitative part estimated the strength of preference for different attributes using an online discrete choice experiment (DCE). DCE data were analyzed using a mixed logit regression model. Qualitative data were collected through individual interviews. A preliminary coding framework was developed which was then further refined and applied during thematic analysis of factors influencing satisfaction and adherence. RESULTS: A total of 101 PLWH took part in the quantitative part and 31 in the qualitative part. Over 90% had an undetectable viral load. Quantitative data revealed a strong preference for a treatment with limited drug-drug interactions, diarrhea and long-term health problems (P<0.0001), and that did not need to be taken on an empty stomach (P<0.0001). Patients also preferred to avoid problems associated with treatment failure (P<0.0001) or one that left them with a higher viral load after the first weeks of treatment (P=0.044). Differences in CD4 cell count, and pills that must be taken with food were not significant drivers of treatment choice. The strength of these attributes was reflected in the qualitative data, highlighting the importance patients place on treatment efficacy, and also suggesting that some of these attributes may impact adherence. Many factors influencing adherence and satisfaction with treatment were identified, including pill size, worry about sexual transmission and impact on social life. CONCLUSION: Most of the attributes included in this survey were important to participants when choosing an ART, in particular those related to quality of life, and these should be taken into account in order to optimize adherence and satisfaction.

A discrete choice experiment to determine UK patient preference for attributes of disease modifying treatments in Multiple Sclerosis.

AIMS: The recent licensing of Disease Modifying Treatments (DMTs) for Multiple Sclerosis (MS) has increased available treatment options. The aim of this study was to explore MS patients' preference for the different attributes of DMTs in the UK. MATERIALS AND METHODS: Attributes (treatment characteristics) for inclusion in the discrete choice experiment (DCE) were determined through published literature and interviews with 12 people with MS. Seven attributes were selected. Participants were presented with three hypothetical treatment options sampled from included attributes and asked for their most/least preferred options. The influence of patient characteristics and demographics on patient preference was also investigated. RESULTS: The DCE was completed by 350 people with MS (81% female, mean age = 39). Results showed that method of taking medication was the strongest determinant of preference (27%; relative importance out of 100%), followed by relapse free rate (21%) and symptom progression (14%). Risk of fatigue (8%) and type of monitoring (6%) were the weakest determinants of preference. Once-daily oral treatment was preferred over all other methods of administration. Participant characteristics did not influence data on strength of preference. LIMITATIONS: This study assumed adequate participant understanding of the discrete choice experiment task, and recruitment targeted those with access to the internet. CONCLUSIONS: These results, derived from people with MS in the UK, should be used to inform individual discussions with patients about DMT choices.