Remote pulmonary rehabilitation for interstitial lung disease: developing the model using experience-based codesign.

BACKGROUND: Remote delivery may improve access to pulmonary rehabilitation (PR). Existing studies are largely limited to individuals with COPD, and the interventions have lacked codesign elements to reflect the needs and experiences of people with chronic respiratory disease, their carers/families and healthcare professionals. The aim of this study was, using experience-based codesign (EBCD), to collaborate with people with interstitial lung disease (ILD), their carers/families and healthcare professionals, to codesign a remote PR programme ready for testing in a future study. METHODS: EBCD comprises interviews, stakeholder workshops and codesign meetings. One-to-one videorecorded interviews with purposively selected people with ILD with experience of PR, their carers/families and healthcare professionals, were edited into a 20 min film. The film was shown at three audiorecorded stakeholder feedback events to identify key themes and touchpoints, and short-list key programme components. The programme was finalised at two further codesign workshops. RESULTS: Ten people with ILD, four carers/families and seven healthcare professionals were interviewed. Participants in the codesign workshops included service-user group: n=14 and healthcare professional group: n=11; joint event: n=21. Final refinements were made with small codesign teams, one comprising three people with ILD and one carer/family member, one with five healthcare professionals. The final codesigned model is a group based, supervised programme delivered by videoconference. Key elements of programme specific to ILD include recommendations to ensure participant safety in the context of desaturation risk, dedicated time for peer support and adaption of the education programme for ILD needs, including signposting to palliative care. CONCLUSION: In this EBCD project, a remote PR programme for people with ILD was codesigned by service-users, their carers/families and multidisciplinary healthcare professionals. Future research should explore the feasibility and acceptability of this intervention.

Five-Repetition Sit-to-Stand Test: Responsiveness and Minimal Important Difference in Idiopathic Pulmonary Fibrosis.

Rationale: Standing from a sitting position is an important activity of daily living. The five-repetition sit-to-stand test (5STS) is a simple physical performance test that measures the fastest time taken to stand five times from a chair with arms folded. It can be measured in most healthcare settings and at home, where traditional field walking tests may not be possible. The 5STS has been validated in community-dwelling older adults and people with chronic obstructive pulmonary disease, but data in idiopathic pulmonary fibrosis (IPF) are limited.Objectives: The aims of this cohort study were to establish the construct validity, responsiveness to pulmonary rehabilitation (PR), and minimal important difference (MID) of the 5STS in IPF.Methods: In 149 people with IPF, we compared the 5STS with measures of lung function, exercise capacity, quadriceps strength, breathlessness, and health-related quality of life. Responsiveness and effect sizes were determined by measuring the 5STS before and after PR. The MID was estimated using anchor- and distribution-based methods.Results: The 5STS correlated significantly with incremental shuttle walk test (ISW) (r = -0.55), isometric quadriceps maximum voluntary contraction (QMVC) (r = -0.45), Medical Research Council dyspnea scale score (r = 0.40), Chronic Respiratory Questionnaire-Total (r = -0.21), and King's Brief Interstitial Lung Disease Questionnaire-Total (r = -0.21) but not forced vital capacity percentage predicted or quadriceps one-repetition maximum (1RM). There was a significant but very weak correlation between change in 5STS and changes in Medical Research Council (r = 0.18), ISW (r = -0.21), and Chronic Respiratory Questionnaire-Total (r = -0.26) but no significant correlation with change in 1RM (r = -0.12) or QMVC (r = -0.18). 5STS time improved with PR (median [25th percentile, 75th percentile] change, -1.97 [-3.47, -0.62] s; P < 0.001). The effect size for the 5STS was 0.66 and higher than quadriceps 1RM, QMVC, and ISW. The mean (range) MID estimate was -1.93 (-1.85 to -2.10) seconds.Conclusions: In people with IPF, the 5STS is a valid physical performance measure that is responsive to exercise-based interventions and suitable for use in most healthcare settings.

Twenty-seven-gauge vitrectomy: a consecutive, single-centre case series with exclusive use over a 4-year period.

BACKGROUND: To assess the safety and effectiveness of the exclusive use of 27-gauge instruments for all vitreoretinal diseases requiring vitrectomy. METHODS: In this retrospective study, 1020 consecutive surgeries were performed on 958 eyes of 848 patients using 27-gauge instruments from March 2017 to June 2021. Patients with a minimum follow-up of 3 months were included. Surgical case-mix, best-corrected visual acuity (BCVA), intraocular pressure (IOP), intra- and post-operative complications, and surgery times were recorded. RESULTS: The study patients were followed up for averagely 11 months. Of the 1020 vitrectomies, 958 were primary procedures. Of the 148 retinal detachment (RD) cases, 138 (93%) required a single vitrectomy. Primary macular hole closure was achieved in 143 of 145 (99%) cases. The average surgical times were 55 and 38 min for RD surgeries and for all other indications, respectively. BCVA improved significantly at the final visit (20/49) compared with the pre-operative visit (20/78) (p < 0.01). IOP was similar at the pre-operative (14.8mmHg) and final (14.3mmHg) visits. Complications recorded include transient hypotony in 39 eyes, iatrogenic retinal breaks in 2 eyes, and a vitreous bleed in 1 other eye. CONCLUSION: This study revealed that 27-gauge vitrectomy instruments can be used for a wide range of indications, with exclusive use in certain settings. The outcomes were similar to other gauges, including for rhegmatogenous retinal detachment, with minimal complications.

Community Pharmacists' Knowledge and Perceptions of Buprenorphine for Patients with Opioid Use Disorder.

OBJECTIVES: The aims of the study are to evaluate community pharmacists' knowledge and perceptions regarding buprenorphine for opioid use disorder and their willingness to dispense buprenorphine and to identify opportunities for education. METHODS: An electronic survey of Michigan pharmacists (n = 11,123) assessed demographics, training, buprenorphine knowledge, dispensing, perceptions of stigma, diversion, and confidence in patient/provider interactions. Composite scores for knowledge, stigma, diversion, and confidence were calculated. Cross-tabulations and logistic regressions examined associations. RESULTS: There were 775 surveys returned (response 7%, n = 11,123) with 390 community pharmacists completing the survey. Twenty-five percent practiced in a rural area. Common practice sites were chain or independent pharmacies (30% each). Ninety-seven percent had buprenorphine training, 50% from Accredited Continuing Pharmacy Education. Eighty percent reported that their pharmacy dispensed buprenorphine with 90% of rural pharmacists compared with 71% urban responding yes. Composite knowledge scores did not differ between urban or rural location ( P > 0.05). Predictors of willingness to dispense buprenorphine were urban location (odds ratio, OR, 0.55; 95% confidence interval [CI], 0.34-0.91; P = 0.01), independent pharmacy (OR, 0.53; 95% CI, 0.30-0.94; P = 0.03), Accredited Continuing Pharmacy Education training (OR, 0.54; 95% CI, 0.34-0.87; P = 0.01), low stigma/diversion (OR, 0.51; 95% CI, 0.37-0.70; P = 0.00), and confidence in patient/provider interactions (OR, 0.14; 95% CI, 0.10-0.19; P = 0.00). CONCLUSIONS: Most survey pharmacists practice at pharmacies that dispense buprenorphine for opioid use disorder, with a larger proportion from rural pharmacies reporting availability. Pharmacists at independent pharmacies in urban locations have increased willingness to dispense buprenorphine, with urban pharmacists having lower perceptions of diversion compared with rural. Differences in buprenorphine availability, pharmacist willingness to dispense, and perceptions are opportunities for education. Limitations include one state, response bias, self-assessed competencies, and small samples.

Prevalence of swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19: the PHOSP-COVID analysis.

OBJECTIVE: Identify prevalence of self-reported swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19. DESIGN: Multicentre prospective observational cohort study using questionnaire data at visit 1 (2-7 months post discharge) and visit 2 (10-14 months post discharge) from hospitalised patients in the UK. Lasso logistic regression analysis was undertaken to identify associations. SETTING: 64 UK acute hospital Trusts. PARTICIPANTS: Adults aged >18 years, discharged from an admissions unit or ward at a UK hospital with COVID-19. MAIN OUTCOME MEASURES: Self-reported swallow, communication, voice and cognitive compromise. RESULTS: Compromised swallowing post intensive care unit (post-ICU) admission was reported in 20% (188/955); 60% with swallow problems received invasive mechanical ventilation and were more likely to have undergone proning (p=0.039). Voice problems were reported in 34% (319/946) post-ICU admission who were more likely to have received invasive (p<0.001) or non-invasive ventilation (p=0.001) and to have been proned (p<0.001). Communication compromise was reported in 23% (527/2275) univariable analysis identified associations with younger age (p<0.001), female sex (p<0.001), social deprivation (p<0.001) and being a healthcare worker (p=0.010). Cognitive issues were reported by 70% (1598/2275), consistent at both visits, at visit 1 respondents were more likely to have higher baseline comorbidities and at visit 2 were associated with greater social deprivation (p<0.001). CONCLUSION: Swallow, communication, voice and cognitive problems were prevalent post hospitalisation for COVID-19, alongside whole system compromise including reduced mobility and overall health scores. Research and testing of rehabilitation interventions are required at pace to explore these issues.

Meditative movement for breathlessness in advanced COPD or cancer: a systematic review and meta-analysis.

The effect of meditative movement, which includes yoga, tai chi and qi gong, on breathlessness in advanced disease is unknown. This systematic review aims to comprehensively assess the evidence on the effect of meditative movement on breathlessness (primary outcome), health-related quality of life, exercise capacity, functional performance and psychological symptoms (secondary outcomes) in advanced disease. 11 English and Chinese language databases were searched for relevant trials. Risk of bias was assessed using the Cochrane tool. Standardised mean differences (SMDs) with 95% confidence intervals were computed. 17 trials with 1125 participants (n=815 COPD, n=310 cancer), all with unclear or high risk of bias, were included. Pooled estimates (14 studies, n=671) showed no statistically significant difference in breathlessness between meditative movement and control interventions (SMD (95% CI) 0.10 (-0.15-0.34); Chi2=30.11; I2=57%; p=0.45), irrespective of comparator, intervention or disease category. Similar results were observed for health-related quality of life and exercise capacity. It was not possible to perform a meta-analysis for functional performance and psychological symptoms. In conclusion, in people with advanced COPD or cancer, meditative movement does not improve breathlessness, health-related quality of life or exercise capacity. Methodological limitations lead to low levels of certainty in the results.

Mood disorder in idiopathic pulmonary fibrosis: response to pulmonary rehabilitation.

Background: Pulmonary rehabilitation improves mood disorder in COPD, but there are limited data in idiopathic pulmonary fibrosis (IPF). The aims of this cohort study were to investigate whether pulmonary rehabilitation reduces mood disorder in IPF, and estimate the minimal important difference (MID) of the Hospital Anxiety and Depression Scale (HADS). Methods: HADS and core pulmonary rehabilitation outcomes were measured in 166 participants before and after an 8-week, in-person, outpatient pulmonary rehabilitation programme. Anchor- and distribution-based methods were used to calculate the MID of HADS-Anxiety (A) and HADS-Depression (D). Results: Suggestive or probable anxiety and depression (HADS ≥8) were present in 35% and 37% of participants, respectively, at baseline, and this reduced significantly following pulmonary rehabilitation (post-pulmonary rehabilitation: HADS-A 23%, HADS-D 26%). Overall, there was a significant reduction in HADS-D (mean change -1.1, 95% CI -1.6- -0.5), but not HADS-A (-0.6, -1.3-0.15) with pulmonary rehabilitation. Subgroup analysis of those with HADS ≥8 revealed significant improvements in HADS domains (mean change: HADS-A -4.5, 95% CI -5.7- -3.4; median change: HADS-D -4.0, interquartile range -6.0- -1.0). The mean (range) MID estimates for HADS-A and HADS-D were -2 (-2.3- -1.7) and -1.2 (-1.9- -0.5), respectively. Conclusion: In people with IPF and suggestive or probable mood disorder, pulmonary rehabilitation reduces anxiety and depression.

Change in gait speed and adverse outcomes in patients with idiopathic pulmonary fibrosis: A prospective cohort study.

BACKGROUND AND OBJECTIVE: Gait speed is associated with survival in individuals with idiopathic pulmonary fibrosis (IPF). The extent to which four-metre gait speed (4MGS) decline predicts adverse outcome in IPF remains unclear. We aimed to examine longitudinal 4MGS change and identify a cut-point associated with adverse outcome. METHODS: In a prospective cohort study, we recruited 132 individuals newly diagnosed with IPF and measured 4MGS change over 6 months. Death/first hospitalization at 6 months were composite outcome events. Complete data (paired 4MGS plus index event) were available in 85 participants; missing 4MGS data were addressed using multiple imputation. Receiver-Operating Curve plots identified a 4MGS change cut-point. Cox proportional-hazard regression assessed the relationship between 4MGS change and time to event. RESULTS: 4MGS declined over 6 months (mean [95% CI] change: -0.05 [-0.09 to -0.01] m/s; p = 0.02). A decline of 0.07 m/s or more in 4MGS over 6 months had better discrimination for the index event than change in 6-minute walk distance, forced vital capacity, Composite Physiologic Index or Gender Age Physiology index. Kaplan-Meier curves demonstrated a significant difference in time to event between 4MGS groups (substantial decline: >-0.07 m/s versus minor decline/improvers: ≤-0.07 m/s; p = 0.007). Those with substantial decline had an increased risk of hospitalization/death (adjusted hazard ratio [95% CI] 4.61 [1.23-15.83]). Similar results were observed in multiple imputation analysis. CONCLUSION: In newly diagnosed IPF, a substantial 4MGS decline over 6 months is associated with shorter time to hospitalization/death at 6 months. 4MGS change has potential as a surrogate endpoint for interventions aimed at modifying hospitalization/death.

Exploration of Novel Scaffolds Targeting Cytochrome b of Pyricularia oryzae.

The fulfilment of the European "Farm to Fork" strategy requires a drastic reduction in the use of "at risk" synthetic pesticides; this exposes vulnerable agricultural sectors-among which is the European risiculture-to the lack of efficient means for the management of devastating diseases, thus endangering food security. Therefore, novel scaffolds need to be identified for the synthesis of new and more environmentally friendly fungicides. In the present work, we employed our previously developed 3D model of P. oryzae cytochrome bc1 (cyt bc1) complex to perform a high-throughput virtual screening of two commercially available compound libraries. Three chemotypes were selected, from which a small collection of differently substituted analogues was designed and synthesized. The compounds were tested as inhibitors of the cyt bc1 enzyme function and the mycelium growth of both strobilurin-sensitive (WT) and -resistant (RES) P. oryzae strains. This pipeline has permitted the identification of thirteen compounds active against the RES cyt bc1 and five compounds that inhibited the WT cyt bc1 function while inhibiting the fungal mycelia only minimally. Serendipitously, among the studied compounds we identified a new chemotype that is able to efficiently inhibit the mycelium growth of WT and RES strains by ca. 60%, without inhibiting the cyt bc1 enzymatic function, suggesting a different mechanism of action.

Frailty and Mortality Risk in COPD: A Cohort Study Comparing the Fried Frailty Phenotype and Short Physical Performance Battery.

Background: Identifying frailty in people with chronic obstructive pulmonary disease (COPD) is deemed important, yet comparative characteristics of the most commonly used frailty measures in COPD are unknown. This study aimed to compare how the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB) characterise frailty in people with stable COPD, including prevalence of and overlap in identification of frailty, disease and health characteristics of those identified as living with frailty, and predictive value in relation to survival time. Methods: Cohort study of people with stable COPD attending outpatient clinics. Agreement between frailty classifications was described using Cohen's Kappa. Disease and health characteristics of frail versus not frail participants were compared using t-, Mann-Whitney U and Chi-Square tests. Predictive value for mortality was examined with multivariable Cox regression. Results: Of 714 participants, 421 (59%) were male, mean age 69.9 years (SD 9.7), mean survival time 2270 days (95% CI 2185-2355). Similar proportions were identified as frail using the FFP (26.2%) and SPPB (23.7%) measures; classifications as frail or not frail matched in 572 (80.1%) cases, showing moderate agreement (Kappa = 0.469, SE = 0.038, p < 0.001). Discrepancies seemed driven by FFP exhaustion and weight loss criteria and the SPPB balance component. People with frailty by either measure had worse exercise capacity, health-related quality of life, breathlessness, depression and dependence in activities of daily living. In multivariable analysis controlling for the Age Dyspnoea Obstruction index, sex, BMI, comorbidities and exercise capacity, both the FFP and SPPB had predictive value in relation to mortality (FFP aHR = 1.31 [95% CI 1.03-1.66]; SPPB aHR = 1.29 [95% CI 0.99-1.68]). Conclusion: In stable COPD, both the FFP and SPPB identify similar proportions of people living with/without frailty, the majority with matching classifications. Both measures can identify individuals with multidimensional health challenges and increased mortality risk and provide additional information alongside established prognostic variables.

The effect of COVID rehabilitation for ongoing symptoms Post HOSPitalisation with COVID-19 (PHOSP-R): protocol for a randomised parallel group controlled trial on behalf of the PHOSP consortium.

INTRODUCTION: Many adults hospitalised with COVID-19 have persistent symptoms such as fatigue, breathlessness and brain fog that limit day-to-day activities. These symptoms can last over 2 years. Whilst there is limited controlled studies on interventions that can support those with ongoing symptoms, there has been some promise in rehabilitation interventions in improving function and symptoms either using face-to-face or digital methods, but evidence remains limited and these studies often lack a control group. METHODS AND ANALYSIS: This is a nested single-blind, parallel group, randomised control trial with embedded qualitative evaluation comparing rehabilitation (face-to-face or digital) to usual care and conducted within the PHOSP-COVID study. The aim of this study is to determine the effectiveness of rehabilitation interventions on exercise capacity, quality of life and symptoms such as breathlessness and fatigue. The primary outcome is the Incremental Shuttle Walking Test following the eight week intervention phase. Secondary outcomes include measures of function, strength and subjective assessment of symptoms. Blood inflammatory markers and muscle biopsies are an exploratory outcome. The interventions last eight weeks and combine symptom-titrated exercise therapy, symptom management and education delivered either in a face-to-face setting or through a digital platform ( www.yourcovidrecovery.nhs.uk ). The proposed sample size is 159 participants, and data will be intention-to-treat analyses comparing rehabilitation (face-to-face or digital) to usual care. ETHICS AND DISSEMINATION: Ethical approval was gained as part of the PHOSP-COVID study by Yorkshire and the Humber Leeds West Research NHS Ethics Committee, and the study was prospectively registered on the ISRCTN trial registry (ISRCTN13293865). Results will be disseminated to stakeholders, including patients and members of the public, and published in appropriate journals. Strengths and limitations of this study • This protocol utilises two interventions to support those with ongoing symptoms of COVID-19 • This is a two-centre parallel-group randomised controlled trial • The protocol has been supported by patient and public involvement groups who identified treatments of symptoms and activity limitation as a top priority.

Pilot study of physiotherapist-led versus music therapist-led breathing control exercises for young adults living with breathing pattern disorder: a randomised controlled trial protocol.

INTRODUCTION: Breathing pattern disorder (BPD) is an abnormal breathing pattern associated with biochemical, biomechanical and psychophysiological changes. While physiotherapy is often offered, limited evidence-based therapies for BPD are available. Music therapy-based singing exercises have been shown to improve quality of life for individuals with respiratory conditions and may also be beneficial for individuals living with BPD. No study has previously compared these participatory interventions in the treatment of people living with BPD. METHODS AND ANALYSIS: This is a study protocol for an assessor blinded 1:1 randomised controlled trial and qualitative interview study. Forty participants aged 18-40 years who score at least 19 on the Nijmegen Questionnaire (NQ) and do not have any underlying respiratory conditions will be recruited. Participants will be randomised to receive either physiotherapy-led or music therapy-led breathing exercises for 6 weeks. The primary outcome will be between-group difference in NQ post-intervention. Semistructured interviews with a purposive sample of participants will be performed. Qualitative data will be analysed using thematic analysis to better understand participants' intervention and trial experiences. ETHICS AND DISSEMINATION: This study has received ethical approval by Brunel University London College of Health, Medicine and Life Science's Research Ethics Committee (32483-MHR-Mar/2022-38624-3). The anonymised completed dataset will be made available as an open-access file via Brunel University London Figshare and the manuscript containing anonymised patient data will be published in an open-access journal. TRIAL REGISTRATION NUMBER: This trial is registered on the Open Science Framework Registry (https://osf.io/u3ncw).

Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a multicentre study.

BACKGROUND: The number of individuals recovering from severe COVID-19 is increasing rapidly. However, little is known about physical behaviours that make up the 24-h cycle within these individuals. This study aimed to describe physical behaviours following hospital admission for COVID-19 at eight months post-discharge including associations with acute illness severity and ongoing symptoms. METHODS: One thousand seventy-seven patients with COVID-19 discharged from hospital between March and November 2020 were recruited. Using a 14-day wear protocol, wrist-worn accelerometers were sent to participants after a five-month follow-up assessment. Acute illness severity was assessed by the WHO clinical progression scale, and the severity of ongoing symptoms was assessed using four previously reported data-driven clinical recovery clusters. Two existing control populations of office workers and individuals with type 2 diabetes were comparators. RESULTS: Valid accelerometer data from 253 women and 462 men were included. Women engaged in a mean ± SD of 14.9 ± 14.7 min/day of moderate-to-vigorous physical activity (MVPA), with 12.1 ± 1.7 h/day spent inactive and 7.2 ± 1.1 h/day asleep. The values for men were 21.0 ± 22.3 and 12.6 ± 1.7 h /day and 6.9 ± 1.1 h/day, respectively. Over 60% of women and men did not have any days containing a 30-min bout of MVPA. Variability in sleep timing was approximately 2 h in men and women. More severe acute illness was associated with lower total activity and MVPA in recovery. The very severe recovery cluster was associated with fewer days/week containing continuous bouts of MVPA, longer total sleep time, and higher variability in sleep timing. Patients post-hospitalisation with COVID-19 had lower levels of physical activity, greater sleep variability, and lower sleep efficiency than a similarly aged cohort of office workers or those with type 2 diabetes. CONCLUSIONS: Those recovering from a hospital admission for COVID-19 have low levels of physical activity and disrupted patterns of sleep several months after discharge. Our comparative cohorts indicate that the long-term impact of COVID-19 on physical behaviours is significant.

SPACE FOR COPD delivered as a maintenance programme on pulmonary rehabilitation discharge: protocol of a randomised controlled trial evaluating the long-term effects on exercise tolerance and mental well-being.

INTRODUCTION: The benefits achieved during pulmonary rehabilitation (PR) are known to be sustained for 6-12 months after the initial programme. Several maintenance trials have been conducted but were heterogeneous in terms of duration, frequency and labour cost. There is no consensus on one best strategy. SPACE FOR COPD (Self-management Programme of Activity, Coping and Education for Chronic Obstructive Pulmonary Disease) is a home-based self-management programme, which has been shown previously to be effective in primary and secondary care settings and is to be tested here as a maintenance programme. The aim is to evaluate the efficacy of the SPACE FOR COPD programme (manual and group sessions), on exercise tolerance and mental well-being, compared with usual care following PR in patients with COPD. METHODS AND ANALYSIS: A prospective, multicentre, single-blinded randomised controlled trial requiring 116 participants with a clinical diagnosis of COPD who have finished PR within 4 weeks will be randomised 1:1 to either a usual care group or a SPACE FOR COPD programme group. The intervention comprises a home-based manual and 4, 2-hour group sessions adopting motivational interviewing techniques over 12 months. The primary outcome is endurance capacity measured by the Endurance Shuttle Walking Test at 12 months. Secondary outcomes are: maximal exercise capacity, health-related quality of life, mood, patient activation, physical activity, lung function and healthcare costs. The measures will be taken at baseline, 6 and 12 months. Patient interviews and staff focus groups will be conducted to explore barriers, facilitators and views about the intervention at the end of the study. A framework analysis will be used for the interpretation of qualitative data. ETHICS AND DISSEMINATION: The trial was granted ethical approval from Health Research Authority and Health and Care Research Wales (HCRW19/EM/0267 on 10 October 2019). Results will be made available to all stakeholders through a dissemination event, conferences and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ISRCTN30110012.

Co-creating with patients an impact framework across the medicine's life cycle: a qualitative study exploring patients' experiences of involvement in and perceptions of impact measures.

BACKGROUND: The biopharmaceutical industry is challenged with efficiently delivering medicines that patients truly value. This can be addressed by engaging patients and caregivers throughout a medicine's life cycle, ensuring that products meet the needs and expectations of those who take them. While isolated best practice examples of patient engagement exist, they remain relatively ad hoc and not fully embedded within Research & Development (R&D) practices. To encourage more patient engagement, the 'impact' of patient engagement projects (PEP) must be objectively measured and demonstrated. Some frameworks have been proposed; however, there is no evidence of widespread adoption, nor have patients' perspectives been robustly explored. The objective of this qualitative study was therefore to understand patients' perspectives of impact measurement that can be systematically applied within a biopharmaceutical company. METHODS: Semi-structured interviews were conducted with 13 patient organisation (PO) representatives exploring their experiences of engagement and reflections on 23 candidate patient engagement impact measures categorised into five groups: Medicines R&D Priorities; Clinical Trial Design; Regulatory & Market Access Submissions; Product Support & Information; and Disease Support & Information. Thematic analysis was undertaken and impact measures revised in line with interview participant feedback. Emerging themes and revisions to impact measures were validated at a joint workshop with 4 patient advisors representing 4 POs. RESULTS: The study revealed that PO representatives feel a deep sense of accomplishment and ownership when collaborating on PEPs with biopharmaceutical companies. They largely conceptualise 'impact' as positive, tangible and useful outcomes. The revisions made to the pre-defined patient engagement impact measures fell into three broad categories: (1) a requirement for greater context; (2) capturing the nature of patient influence; and (3) terminology changes. The greatest number of revisions concerned 'requiring greater context', for example, including additional descriptions, patient quotes, and satisfaction. CONCLUSIONS: This study sheds light on how patient advocates view 'impact'. Typically this means delivering 'value' important for them. Therefore, the authors of this paper created the term 'value-impact' to comprehensively characterise this conceptualisation, and propose a value-impact measurement plan, incorporating longitudinal data. Through this understanding and in light of other recently published work, wide-scale adoption and implementation of the measurement of value-impact across the biopharmaceutical industry can be realised.

Developing medicines involves multiple stages, all essential for pharmaceutical companies. However, this approach is becoming increasingly costly and patients are rarely involved in defining treatment outcomes. Patient insight is important for everyone involved in medicinal development and required by authorities reviewing new treatments. To identify best practices, the difference ('impact') made by engaging with patients must be measured continuously throughout the treatment development process. Possible impact measures have been proposed (for example, the PARADIGM initiative), but problems remain.This study aimed to work with patients and adapt standard measuring approaches that can be used to provide ongoing insight into the impact of patient engagement activities for companies and patients. Researchers interviewed 13 patient organisation (PO) representatives to explore their experiences of impact measures. Thematic analysis was conducted, and data used to adapt 23 potential impact measures in collaboration with patients.This study identified that PO representatives view impact as being positive, tangible, and useful outcomes, achieving a deep sense of accomplishment and ownership for those patients and representatives involved. The authors created the term 'value-impact' to describe how patients perceive such achievements. Furthermore, measures should be adapted to: 1) include greater context such as descriptions, patients quotes and satisfaction; 2) capture patient influence; and 3) use language that is understandable for all parties. Examples and suggestions for engagement at different stages and revised impact measures are presented in this report. It is our hope that this study will encourage more frequent and effective use of patient engagement strategies as medicines are developed.