Quality Of Patient-reported Outcomes Research Articles

Severe impairment of patient-reported outcomes in patients with chronic hepatitis C virus infection seen in real-world practices across the world: Data from the global liver registry.

Cure of chronic hepatitis C (CHC) can lead to improvement of health-related quality of life and other patient-reported outcomes (PROs). While extensive PRO data for CHC patients who were enrolled in clinical trials are available, similar data for patients seen in real-world practices are scarce. Our aim was to assess PROs of CHC patients enrolled from real-world practices from different regions and to compare them with those enrolled in clinical trials. CHC patients seen in clinical practices and not receiving treatment were enrolled in the Global Liver Registry (GLR). Clinical and PRO (FACIT-F, CLDQ-HCV, WPAI) data were collected and compared with the baseline data from CHC patients enrolled in clinical trials. N=12,171 CHC patients were included (GLR n=3146, clinical trial subjects n=9025). Patients were from 30 countries from 6 out of 7 Global Burden of Disease (GBD) super-regions. Compared with clinical trial enrollees, patients from GLR were less commonly enrolled from High-Income GBD super-region, older, more commonly female, less employed, had more type 2 diabetes, anxiety and clinically overt fatigue but less cirrhosis (all p < 0.001). Out of 15 PRO domain and summary scores, 12 were lower in GLR patients than in subjects enrolled in clinical trials (p < 0.001). In multiple regression models, anxiety, depression, and fatigue were associated with significant PRO impairment in CHC patients (p < 0.05). After adjustment for the clinico-demographic confounders, the association of PRO scores of CHC patients with enrolment settings was no longer significant (all p > 0.05). In conclusion, hepatitis C patients seen in the real-world practices have PRO impairment driven by fatigue and psychiatric comorbidities.

Self-applied topical interventions for melasma: a systematic review and meta-analysis of data from randomized, investigator-blinded clinical trials.

Melasma is a common dermatological condition. Although its relevance as a skin condition is primarily of a cosmetic nature, it may affect the patient's wellbeing and quality of life. A broad range of treatment options is available, which makes it difficult to choose the most appropriate of those treatments. To summarize and critically appraise evidence from investigator-blinded randomized controlled trials (RCTs) on the efficacy and safety of self-applied topical interventions for melasma. We systematically searched MEDLINE and the Cochrane CENTRAL trials database for RCTs on topical, self-administered interventions for patients diagnosed with melasma. Eligibility was limited to RCTs that explicitly stated in their methods section (i) how they generated the random allocation sequence, and (ii) that the study outcome assessor was blinded to the participants' group allocation. Outcomes of interest included evaluator-assessed clinical scores (such as the Melasma Area and Severity Index), quality of life and patient-reported outcomes, as well as safety outcomes. The study findings were meta-analysed, pooling data from studies on the same comparisons, if this was possible. We assessed confidence in effect estimates using the GRADE approach. Our searches yielded 1078 hits. We included 36 studies reporting on 47 different comparisons of interventions. These included medical treatments such as 'triple combination cream' (TCC), over-the-counter cosmetic and herbal products, as well as sun creams covering different light spectra. Pooling data was possible for only two comparisons, topical tranexamic acid (TXA) vs. hydroquinone (HQ) and cysteamine vs. placebo. Direct comparisons were available for a variety of interventions; however, the reported outcomes varied greatly. Overall, our confidence in the effect estimates ranged from very low to high. Our findings indicate that TCC and its individual components HQ and tretinoin are effective in lightening melasma. Besides these established self-applied treatment options, we identified further medical treatments as well as promising cosmetic and herbal product treatment approaches. Furthermore, evidence suggests that using broad-spectrum sunscreen covering both the visible and ultraviolet-light spectrum enhances the treatment efficacy of HQ. However, with mostly small RCTs comparing treatments directly using a broad range of outcomes, further research is needed to draw conclusions about which treatment is most effective. What is already known about this topic? Melasma is a common dermatological disease. Although it is primarily a cosmetic condition, it can severely affect the patient's wellbeing and quality of life. Treatment options for melasma include a broad range of medical, cosmetic and herbal products. Given the large number of available interventions, it is difficult for clinicians and for patients to make informed decisions about which treatment to choose. What does this study add? We systematically assessed data from investigator-blinded randomized controlled trials of self-applied topical interventions. Our GRADE evaluations of confidence in the findings ranged from very low to high and may help clinicians and patients navigate treatment decisions. Besides the established self-applied medical treatment options, we identified promising cosmetic and herbal treatment approaches. Evidence suggests sunscreen covering the ultraviolet (UV)- and visible light spectra increases treatment efficacy compared with UV-only protection.

A Delphi Consensus on Patient Reported Outcomes for Registries and Trials Including Patients with Intermittent Claudication: Recommendations and Reporting Standard

This study aimed to develop a core set of patient reported outcome quality indicators (QIs) for the treatment of patients with intermittent claudication (IC), that allow a broad international implementation across different vascular registries and within trials. A rigorous modified two stage Delphi technique was used to promote consensus building on patient reported outcome QIs among an expert panel consisting of international vascular specialists, patient representatives, and registry members of the VASCUNET and the International Consortium of Vascular Registries. Potential QIs identified through an extensive literature search or additionally proposed by the panel were validated by the experts in a preliminary survey and included for evaluation. Consensus was reached if ≥ 80% of participants agreed that an item was both clinically relevant and practical. Participation rates in two Delphi rounds were 66% (31 participants of 47 invited) and 90% (54 of 60), respectively. Initially, 145 patient reported outcome QIs were documented. Following the two Delphi rounds, 18 quality indicators remained, all of which reached consensus regarding clinical relevance. The VascuQoL questionnaire (VascuQoL-6), currently the most common patient reported outcome measurement (PROM) used within vascular registries, includes a total of six items. Five of these six items also matched with high rated indicators identified in the Delphi study. Consequently, the panel recommends the use of the VascuQoL-6 survey as a preferred core PROM QI set as well as an optional extension of 12 additional patient reported QIs that were also identified in this study. The current recommendation based on the Delphi consensus building approach, strengthens the international harmonisation of registry data collection in relation to patient reported outcome quality. Continuous and standardised quality assurance will ensure that registry data may be used for future quality benchmarking studies and, ultimately, positively impact the overall quality of care provided to patients with peripheral arterial occlusive disease.

Integrated traditional Chinese medicine intervention for delaying HIV morbidity: study protocol for a multicentre randomised controlled trial

BackgroundAcquired immune deficiency syndrome is caused by humans and is high worldwide. Active antiretroviral therapy emerged in the late 1990s and is effective against AIDS. However, despite the extensive research on AIDS, there is still no vaccine or cure. The benefits of traditional Chinese medicine (TCM) for AIDS are increasingly recognised, especially by patients with asymptomatic HIV infection.Methods/designThe proposed trial will enrol 216 eligible patients who will be randomised into treatment and control groups. After 72 weeks of intervention, the efficacy and safety of TCM for patients with AIDS will be assessed. The variables that will be measured include clinical symptoms, TCM syndromes, viral load, immunological indicators, inflammatory factors, quality of life, patient-reported outcomes and safety assessment.DiscussionThe study aim to compare the effectiveness and safety of TCM for asymptomatic AIDS and explore its potential underlying mechanism. Additionally, the findings will provide a reference for the use of TCM to delay the onset and control the progression of HIV/AIDS.Trial registrationChinese Clinical Trial Registry ChiCTR1800018365. Registered on 13 September 2018

Health-related quality of life analysis in ovarian cancer clinical trials involving PARP inhibitors: a critical methodological perspective.

The poly (ADP-ribose) polymerase inhibitors (PARPi) have yielded significant clinical benefits as maintenance therapy in women with newly diagnosed and relapsed platinum-sensitive advanced ovarian cancer. These drugs were approved based on progression-free survival, the primary endpoint of their respective pivotal trials. Health-related quality of life (HRQoL) and/or patient-reported outcomes were included in these trials as a secondary exploratory endpoint. Nevertheless, many weaknesses in the analysis of HRQoL across these trials can be noticed. Heterogeneity and suboptimal HRQoL analysis in oncology trials contribute to misconceptions about this endpoint among oncologists and prevent quality of life as being an endpoint used for approvals. In this article, we discuss these HRQoL results from a methodological perspective and propose some solutions for improvement that could be used by regulatory and academic institutions running ovarian cancers trials. Notably, we suggest to measure and analyze HRQoL data after disease progression, to focus dedicated papers on the statistical analyses of HRQoL recommended by the SISAQOL consortium (linear mixed model for repeated measures and time-to-event approaches) and to communicate on available guidelines to ensure compliance with best international practices regarding the measurement and analysis of HRQoL.

The impact of delayed wound healing on patient-reported outcomes after breast cancer surgery

Postoperative complications after breast cancer surgery may be associated with decreased quality of life. It remains unclear whether oncoplastic breast-conserving surgery or mastectomy with reconstruction lead to more postoperative complications than conventional breast surgery (CBS). As delayed wound healing (DWH) is one of the most frequent minor complications, we sought to investigate the significance of DWH for patient-reported outcomes after oncoplastic, reconstructive, and CBS. Our study is a retrospective cohort study of consecutive patients with stage I-II breast cancer who underwent oncoplastic or CBS performed by three breast surgeons at a single tertiary referral hospital from June 2011 until May 2019. Patient-reported outcomes were evaluated postoperatively using the BREAST-Q questionnaire. Comparisons were made between patients with and without DWH. A total of 229 patients who met the inclusion criteria and 28 (12%) of them developed DWH, 27/158 (17%) in the oncoplastic breast-conserving surgery and reconstruction group and 1/71 (1%) in the CBS group. The mean time from surgery to BREAST-Q assessment was comparable in both groups (29 months in the DWH vs. 33 months in the normal wound healing group). No statistically significant difference for any BREAST-Q scale was detected between patients with and without DWH. This includes physical (p=0.183), psychosocial (p=0.489), sexual well-being (p=0.895), and satisfaction with breasts (p=0.068). Our study confirms that oncoplastic breast-conserving surgery and mastectomy with reconstruction lead to significantly more DWH than CBS. However, neither quality of life nor patient-reported outcomes following state-of-the-art reconstructive or oncoplastic breast-conserving surgery at a specialized center seem to be compromised.

A prospective, randomized trial of patient-reported outcome measures to drive management decisions in hematology and oncology

BackgroundClinicians have limited time during patient encounters which can result in patients' concerns not being addressed. This study's objective was to test whether an electronic patient-reported outcome quality of life tool (PROQOL) in which patients identify their primary concern during clinic visits improves cancer patient quality of life (QOL). Patients and methodsThis single center non-blinded prospective clinical trial randomized patients (2:1) to PROQOL versus usual care (UC). Two patient cohorts were enrolled: those with hematologic malignancies (multiple myeloma [MM] or light chain amyloidosis [AL]) and solid tumors (head and neck [H/N] or gynecologic [GYN] malignancies). Primary endpoint was patient-reported QOL at 12 months measured by a single-item Linear Analog Self-Assessment. Value to patients and impact on clinician workflow was measured using a “was it worth it” survey. The study was powered to detect a 0.5 standard deviation difference between groups. ResultsOverall 383 patients were enrolled, 171 with MM, 62 AL, 113 GYN, and 37 H/N between July 2016 and April 2018, with 12-month follow-up. There were 171 (44.6%) male patients and median age was 62 years (range 31–87). The most often selected concern was physical health (30.9%), and second was cancer diagnosis and treatment (29.1%). Mean QOL was 7.12 for PROQOL and 6.98 for UC (0–10 scale) at 12 months, with no between-group difference overall (p = 0.56) or within hematologic or solid tumor cohorts, respectively. Among patients, 74% thought the PROQOL tool was worthwhile, 86% would choose PROQOL again, and 81% would recommend it to others. Among clinicians, 95% responded that PROQOL was worthwhile and did not think that PROQOL negatively impacted their workflow. ConclusionsAlthough we did not demonstrate a QOL difference between PROQOL and UC groups; the PROQOL tool held considerable value in identifying patients' main concerns over time and was worthwhile for patients and clinicians.

Breast Reconstruction: Impact of the Procedure on Quality of Life

English Breast cancer and the surgical procedures associated with it have a major impact on the quality of life of affected patients. Research shows that the loss of the breast and the associated change in body image have a major impact on the female self-image for many women. This has a strong negative impact on the quality of life of those affected. With modern clinical outcome research including treatment results from the patient's perspective in the form of patient-reported outcome measures (PROMs), the satisfaction and quality of life of those affected can be measured, analysed and compared. This review examines the extent to which breast reconstruction improves the quality of life for many women and how the different reconstruction methods vary in their impact on quality of life and satisfaction. In addition, the review discusses the importance of standardised recording and analysis of PROMs in combination with objective clinical data and their integration into the treatment process, and it demonstrates implementation options. Such systematic recording of PROMs enables the creation of databases and registers, the evaluation of which provides information that can be used for scientific and clinical purposes. Based on these research results, prognostic models can be created and treatment results can be examined in comparative studies facilitating clinical decision-making and quality controls.

Quality of patient-reported and proxy-reported outcomes for children with impairment of the lower extremity: systematic review protocol

IntroductionAs patient-reported outcome measures (PROMs) have become of significant importance in evaluation of care and clinical research, adequately selecting the appropriate instrument is an integral part of paediatric orthopaedic research...

Quality of Life and Other Patient-Reported Outcomes Across the Life Span Among People With Fontan Palliation.

Traditional congenital heart disease (CHD) outcomes include mortality (survival to adulthood and life expectancy) as well as cardiac and noncardiac morbidity. Strategies to identify and manage sequelae have primarily focused on objective data obtained though invasive and noninvasive diagnostic approaches. In contrast, patient-reported outcomes (PROs) provide subjective information, using standardized measures, about patients' health and well-being as reported directly by patients, without interpretation, interference, or assumptions made by clinicians or others. Selection of PRO measures entails thoughtful consideration of who the individuals being surveyed are, why assessment is occurring (eg, what are the domains of interest; clinical vs research), and what processes are in place for acquisition, administration, interpretation, and response. In this review, we focus on 3 domains of PROs for pediatric and adult patients with Fontan physiology: physical health status, psychological functioning, and quality of life. Infants, children, adolescents, and adults with CHD face a spectrum of challenges that might influence PROs across the life span. In general, patients with Fontan palliation tend to have lower physical health status, experience more psychological distress, and have equivalent or reduced quality of life compared with healthy peers. Herein, we provide an overview of PROs among people with Fontan circulation as a group, yet simultaneously emphasize that the optimal way to understand the experiences of any individual patient is to ask and listen. We also offer clinical and research initiatives to improve the adoption and utility of PROs in CHD settings, which show commitment to capturing, understanding, and responding to the patient voice.

PCR67 Association of Walking Distance with Quality of Life and Other Patient-Reported Outcomes in Pompe Disease

Timed walking tests in clinical studies of certain rare muscular disorders are important efficacy measures appraised in health technology assessments (HTA). We explored whether the six-minute walk distance (6MWD) was associated with various patient-reported outcomes (PROs), including quality of life, in Pompe Disease (PD) – a rare muscular disorder.

The burden of non-alcoholic steatohepatitis: A systematic review of health-related quality of life and patient-reported outcomes

Background & AimsNon-alcoholic steatohepatitis (NASH) is associated with increased mortality and a high clinical burden. NASH adversely impacts patients’ health-related quality of life (HRQoL), but published data on the humanistic burden of disease are limited. This review aimed to summarise and critically evaluate studies reporting HRQoL or patient-reported outcomes (PROs) in populations with NASH and identify key gaps for further research.MethodsMedline, EMBASE, the Cochrane Library and PsycINFO were searched for English-language publications published from 2010 to 2021 that reported HRQoL/PRO outcomes of a population or subpopulation with NASH.ResultsTwenty-five publications covering 23 unique studies were identified. Overall, the data showed a substantial impact of NASH on HRQoL, particularly in terms of physical functioning and fatigue, with deterioration of physical and mental health as NASH progresses. Prevalent symptoms, including fatigue, abdominal pain, anxiety/depression, cognition problems, and poor sleep quality, adversely impact patients’ ability to work and perform activities of daily living and the quality of relationships. However, some patients fail to attribute symptoms to their disease because of a lack of patient awareness and education. NASH is associated with high rates of comorbidities such as obesity and type 2 diabetes, which contribute to reduced HRQoL. Studies were heterogeneous in terms of diagnostic methods, population, outcomes, follow-up time, and measures of HRQoL/utility. Most studies were rated ‘moderate’ at quality assessment, and all evaluable studies had inadequate control of confounders.ConclusionsNASH is associated with a significant HRQoL burden that begins early in the disease course and increases with disease progression. More robust studies are needed to better understand the humanistic burden of NASH, with adequate adjustment for confounders that could influence outcomes.Lay summaryNon-alcoholic steatohepatitis (NASH) has a significant impact on quality of life, with individuals experiencing worse physical and mental health compared with the general population. NASH and its symptoms, which include tiredness, stomach pain, anxiety, depression, poor focus and memory, and impaired sleep, affect individuals’ relationships and ability to work and perform day-to-day tasks. However, not all patients are aware that their symptoms may be related to NASH. Patients would benefit from more education on their disease, and the importance of good social networks for patient health and well-being should be reinforced. More studies are needed to better understand the patient burden of NASH.

Randomized controlled trial (RCT) of symptom screening with targeted early palliative care (STEP) versus usual care in patients with advanced cancer.

e24084 Background: To direct limited specialized palliative care resources to patients in greatest need, we developed STEP (Symptom screening with Targeted Early Palliative care). STEP entails symptom screening (ESAS-r) at each oncology clinic visit and triggered alerts (for moderate-high physical and psychological symptoms) to a nurse who calls the patient to offer a palliative care clinic (PCC) visit. We conducted a phase III RCT to assess the impact of STEP versus usual care on quality of life and other patient-reported outcomes (PROs). Methods: Adults with advanced cancer were recruited from medical oncology clinics at the Princess Margaret Cancer Centre, Toronto, Canada. Consenting patients with oncologist-assessed ECOG 0-2 and estimated survival of 6-36 months were enrolled and block randomized (stratified by tumour site and symptom severity) to STEP or usual care. Participants completed measures of quality of life (FACT-G7), depression (PHQ-9), symptom control (ESASr-CS), and satisfaction with care (FAMCARE-P16) at baseline, 2, 4 and 6 months. The primary outcome was FACT-G7 at 6 months, with a planned sample size of 261/arm. Results: From 8/2019 to 3/2020, 69 patients were enrolled: 33 randomized to STEP and 36 to usual care. The trial was then halted permanently due to the COVID-19 pandemic, owing to substantial changes to elements of STEP (shift to virtual symptom screening and palliative care) and usual care (shift to virtual oncology care). Median age was 64 years (range 25-87) and 62% (43/69) were women; study arms were balanced at baseline except gender, with more women randomized to STEP. Within the STEP arm, 20 (61%) participants triggered a nurse’s call to offer a PCC visit, of whom 13 attended the clinic at least once. All outcomes tended to be better in the STEP arm compared to usual care, particularly depression and satisfaction with care at 6 months; however, results were not statistically significant (Table). Conclusions: STEP holds promise for improving quality of life and other PROs in patients with advanced cancer and effectively directing early palliative care towards those who need it most. In response to the pandemic, an online version of STEP has been developed and a further trial is in progress. Clinical trial information: NCT03987906. [Table: see text]

Current Status and Future Perspective on the Management of Lymph Node-Positive Prostate Cancer after Radical Prostatectomy.

Simple SummarypN1 after RP with PLND represents one of the most unfavorable prognostic factors for disease recurrence and cancer-specific mortality in prostate cancer. Treatment intensification may reduce risks of recurrence and cancer-specific mortality, but it may increase adverse events and impair quality of life. However, optimal management for pN1 patients remains unclear. Nevertheless, few randomized control trials for pN1 are under investigation, and then more research is needed to establish an optimal therapeutic strategy for patients with pN1. This review summarizes current evidence on the treatments available for men with pN1, summarizes RCTs that included pN1 prostate cancer, and also discusses future perspectives.Pathological lymph node involvement (pN1) after a pelvic lymph node dissection represents one of the most unfavorable prognostic factors for disease recurrence and cancer-specific mortality in prostate cancer. However, optimal management for pN1 patients remains unclear. Thus, the guideline from the European Association of Urology recommends discussing three following management options with pN1 patients after an extended pelvic lymph node dissection, based on nodal involvement characteristics: (i) offer adjuvant androgen-deprivation therapy, (ii) offer adjuvant androgen-deprivation therapy with additional radiotherapy and (iii) offer observation (expectant management) to a patient with ≤2 nodes and a prostate-specific antigen <0.1 ng/mL. Treatment intensification may reduce risks of recurrence and cancer-specific mortality, but it may increase adverse events and impair quality of life. Few randomized control trials for pN1 are under investigation. In addition, there are limited reports on the quality of life and patient-reported outcomes in patients with pN1. Therefore, more research is needed to establish an optimal therapeutic strategy for patients with pN1. This review summarizes current evidence on the treatments available for men with pN1, summarizes randomized control trials that included pN1 prostate cancer, and discusses future perspectives.

Relating person-centredness to quality-of-life assessments and patient-reported outcomes in healthcare: A critical theoretical discussion.

Engagement with the historical and theoretical underpinnings of measuring quality of life (QoL) and patient‐reported outcomes (PROs) in healthcare is important. Ideas and values that shape such practices—and in the endgame, people's lives—might otherwise remain unexamined, be taken for granted or even essentialized. Our aim is to explicate and theoretically discuss the philosophical tenets underlying the practices of QoL assessment and PRO measurement in relation to the notion of person‐centredness. First, we engage with the late‐modern history of the concept of QoL and the act of assessing and measuring it. Working with the historical method of genealogy, we describe the development of both QoL assessments and PRO measures (PROMs) within healthcare by accounting for the contextual conditions for their possibility. In this way, the historical and philosophical underpinnings of these measurement practices are highlighted. We move on to analyse theoretical and philosophical underpinnings regarding the use of PROMs and QoL assessments in clinical practice, as demonstrated in review studies thereof. Finally, we offer a critical analysis regarding the state of theory in the literature and conclude that, although improved person‐centredness is an implied driver of QoL assessments and PROMs in clinical practice, enhanced theoretical underpinning of the development of QoL assessments is called for.

Real-world burden of systemic lupus erythematosus in the USA: a comparative cohort study from the Medical Expenditure Panel Survey (MEPS) 2016–2018

ObjectiveSLE is a chronic, multiorgan, autoimmune disease; however, current prevalence estimates are dated and often from non-generalisable patient populations, and quality of life and patient-reported outcomes in the real-world SLE...

School-age outcomes in patients with unilateral coronal synostosis: comparison of fronto-orbital advancement and endoscopic strip craniectomy.

Outcomes research on unilateral coronal synostosis is mostly limited to the early postoperative period. This study examines facial asymmetry, desire for revision, and patient-reported outcomes at school age in children who received either endoscopic strip craniectomy with helmet therapy or fronto-orbital advancement (open repair). Patients with repaired unilateral coronal synostosis born between 2000 and 2017, with 3D photographs taken when they were between 3.5 and 8 years of age, were eligible for study inclusion. Three pairs of bilateral linear measurements and two angular measurements were taken. Parent- and physician-reported desire for revision and patient-reported outcomes (Patient-Reported Outcomes Measurement Information System cognitive function and Quality of Life in Neurological Disorders stigma scores) were collected from patient charts. Thirty-five patients qualified, including 25 with open repair and 10 with endoscopic repair. The median patient ages at repair were 3 months and 8 months in the endoscopic and open groups, respectively. The average ages at final 3D photography were 5.8 years and 5.5 years in the endoscopic and open groups, respectively. Digital anthropometry revealed no significant differences in measures of facial asymmetry between the repair groups (p ≥ 0.211). Midface depth (tragion to subnasale) was significantly less symmetric at school age than other linear measures (F(2,102) = 9.14, p < 0.001). Forehead asymmetry was significantly associated with parent- and physician-reported desire for revision (p ≤ 0.006). No significant associations were found between physical asymmetry and patient-reported stigma or cognitive function (p > 0.046, Holm-Bonferroni correction). Children who underwent open or endoscopic repair for unilateral coronal synostosis have comparable facial symmetry at school age, but midface depth remains highly asymmetrical in both groups. Forehead asymmetry at school age correlates with parent- and physician-reported desire for revision.

P275 Association of the improvement of synovitis and enthesitis with quality of life/patient reported outcomes in patients with psoriatic arthritis treated with ixekizumab

Abstract Background/Aims Psoriatic arthritis (PsA) is an inflammatory rheumatic disease with manifestations including synovitis and enthesitis. During extensive study programs, IXE has shown a treatment effect across domains affected by PsA. Ixekizumab (IXE) is an IL17A inhibitor approved for the treatment of active PsA and axial SpA. We sought to determine whether there is any association between the improvement of synovitis with that of enthesitis from baseline (BL) through week (wk) 52 in patients (pts) with PsA treated with IXE. Additionally, the association between the improvement of synovitis and enthesitis on health-related quality of life and patient-reported outcomes was investigated. Methods Data from SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295) and SPIRIT-H2H (NCT03151551) were analysed. These were randomized, phase 3 trials involving pts with active PsA either biologic DMARD-naïve (P1, H2H) or TNF-inhibitor-experienced (P2). We examined the patient population randomised to IXE-treatment (80 mg of ixekizumab every 4 weeks [IXEQ4W]), that had both synovitis and enthesitis at BL. For each study, a standardisation procedure was applied to each study data in order to overcome the differences in score range between LEI and SJC. The Pearson correlation coefficient between improvement from BL in enthesitis and synovitis was calculated at each time point. The mean improvement in the SF-36 Physical Component Summary score [PCS], the Patient’s Global Assessment of Disease Activity [Pt GA], and the EuroQOL five dimensions [EQ5D]-visual analogue [VAS] score) was calculated over time for pts who reached or did not reach resolution of both enthesitis and synovitis at wk 52. Missing data were imputed with modified Baseline Carried Out Forward (mBOCF) for continuous outcomes. Non-responder imputation was used for pts with missing resolution of enthesitis or synovitis. Results At BL, 68 (63% of patients treated with IXEQ4W in the ITT population), 68 (56%) and 159 (56%) pts from P1, P2 and H2H respectively, had both synovitis and enthesitis. In all 3 trials, the standardized mean change from baseline in synovitis and enthesitis showed a similar pattern over time. When statistically significant, Pearson correlation coefficient values ranged from 0.16 to 0.40, indicating a positive association between mean improvement in synovitis and enthesitis. We observed an improvement of SF-36 over the 52 wks regardless of the resolution of synovitis or enthesitis. The most pronounced improvement was shown by pts achieving resolution of both synovitis and enthesitis, followed by the pts achieving one or the other. Conclusion Across the SPIRIT trials, treatment with IXE led to the significant improvement in synovitis and enthesitis with a positive association between the improvement of both. Furthermore, pts that resolved both measures at wk 52 experienced an earlier and greater improvement in the SF-36 Physical Component Scale. Disclosure D. McGonagle: Corporate appointments; D. McGonagle has undertaken research and/or educational program activity with: AbbVie, Celgene, Johnson &amp; Johnson, Merck Sharp &amp; Dohme, Pfizer, and UCB Pharma. L. Kristensen: Consultancies; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, and UCB Pharma. Member of speakers’ bureau; AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, and UCB Pharma. Grants/research support; Biogen, Janssen Cilag, and UCB Pharma. M. Rudwaleit: Consultancies; AbbVie, Bristol Myers Squibb, Celgene, Chugai Pharmaceutical/Roche, Eli Lilly and Company, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, and UCB Pharma. H. Kameda: Consultancies; AbbVie, Asahi Kasei Pharma, Astellas, Bristol Myers Squibb, Chugai Pharmaceutical, Eisai, Eli Lilly and Company, Janssen, Mitsubishi Tanabe Pharma, Novartis, Sanofi, and Takeda. Member of speakers’ bureau; AbbVie, Asahi Kasei Pharma, Astellas, Bristol Myers Squibb, Chugai Pharmaceutical, Eisai, Eli Lilly and Company, Janssen, Mitsubishi Tanabe Pharma, Novartis, Sanofi, and Takeda. T. Holzkaemper: Shareholder/stock ownership; Eli Lilly and Company. C. El Baou: Other; C. El Baou is an independent contractor working for: Eli Lilly and Company. J. Smolen: Consultancies; AbbVie, Amgen, AstraZeneca, Astro Pharma, Bristol Myers Squibb, Celgene, Celltrion, Chugai Pharmaceutical, Eli Lilly and Company. Grants/research support; Gilead Sciences, GlaxoSmithKline, ILTOO Pharma, Janssen, MedImmune, Merck Sharp &amp; Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, and UCB Pharma.

A Phase II trial of Higher RadiOtherapy Dose In The Eradication of early rectal cancer (APHRODITE): protocol for a multicentre, open-label randomised controlled trial

IntroductionThe standard of care for patients with localised rectal cancer is radical surgery, often combined with preoperative neoadjuvant (chemo)radiotherapy. While oncologically effective, this treatment strategy is associated with operative mortality...

Reducing research wastage by starting off on the right foot: optimally framing the research question.

Strongly framed research questions are clear as to the population (P), the exposures or interventions (E/I), comparison groups (C), outcomes (O), time when relevant (T), and what the investigator wants to know. A solid framework sets up the measurement model, analysis, and anticipated results. The purpose of this study was to estimate the extent to which research questions in journals that focused on patient-reported outcome measures (PROM) and quality of life (QOL) are clear. All 440 research articles published in four PROM journals in 2020. excluding reviews, psychometric, and qualitative papers, were reviewed. Research questions were classified as: (i) adequately framed (ii) poorly framed; or (iii) unframed based on clarity criteria. Examples from each journal were presented and reframed to match results in the article. Of 440 articles, 195 (44.3%) were classified as adequately framed; 230 (52.2%) as poorly framed; and 15 (3.4%) as unframed. There was heterogeneity across journals (Chi-square: 20.8; 6 df; p = 0.002). Only 29% were framed according to what the investigators wanted to know; 72% were framed like a "to do" list; and 6% were framed as a research agenda. Almost half of the questions were poorly framed or unframed a practice that could contribute to research wastage. Even "adequately framed" questions rarely stated what they wanted to know a priori, increasing the risk of biased reporting. Researchers, reviewers, and editors should encourage the use established frameworks for research questions.