Current practices in patient-reported outcome (PRO) data collection in clinical trials:a cross-sectional survey of UK trial staff and management

Objectives Patient-reported outcome measures (PROMs) collected in clinical trials should be administered in a standardised way across sites and routinely screened for avoidable missing data in order to maximise data quality/minimise risk of bias. Recent qualitative findings, however, have raised concerns about the consistency of PROM administration in UK trials. The purpose of this study was to determine the generalisability of these findings across the wider community of trial personnel. Design Online cross-sectional survey. Setting Participants were recruited from 55 UK Clinical Research Collaboration Registered Clinical Trials Units and 19 Comprehensive Local Research Networks. Participants Research nurses, data managers/coordinators, trial managers and chief/principal investigators involved in clinical trials collecting PROMs. Analysis We undertook descriptive analyses of the quantitative data and directed thematic analysis of free-text comments. Factors associated with the management of missing PRO data were explored using logistic regression. Results Survey data from 767 respondents supported the generalisability of qualitative study findings, suggesting inconsistencies in PROM administration with regard to: the level of assistance given to trial participants; the timing of PROM completion in relation to the clinical consultation; and the management of missing data. Having ≥10 years experience in a research role was significantly associated with the appropriate management of missing PROM data (OR 2.26 (95% CI 1.06 to 4.82), p=0.035). There was a consensus that more PROM guidance was needed in future trials and agreement between professional groups about the necessary components. Conclusions There are inconsistencies in the way PROMs are administered by trial staff. Such inconsistencies may reduce the quality of data and have the potential to introduce bias. There is a need for improved guidance in future trials that support trial personnel in conducting optimal PROM data collection to inform patient care

Inconsistencies in quality of life data collection in clinical trials: a potential source of bias? Interviews with research nurses and trialists

BACKGROUND:Patient-reported outcomes (PROs), such as health-related quality of life (HRQL) are increasingly used to evaluate treatment effectiveness in clinical trials, are valued by patients, and may inform important decisions in the clinical setting. It is of concern, therefore, that preliminary evidence, gained from group discussions at UK-wide Medical Research Council (MRC) quality of life training days, suggests there are inconsistent standards of HRQL data collection in trials and appropriate training and education is often lacking. Our objective was to investigate these reports, to determine if they represented isolated experiences, or were indicative of a potentially wider problem. METHODS AND FINDINGS:We undertook a qualitative study, conducting 26 semi-structured interviews with research nurses, data managers, trial coordinators and research facilitators involved in the collection and entry of HRQL data in clinical trials, across one primary care NHS trust, two secondary care NHS trusts and two clinical trials units in the UK. We used conventional content analysis to analyze and interpret our data. Our study participants reported (1) inconsistent standards in HRQL measurement, both between, and within, trials, which appeared to risk the introduction of bias; (2), difficulties in dealing with HRQL data that raised concern for the well-being of the trial participant, which in some instances led to the delivery of non-protocol driven co-interventions, (3), a frequent lack of HRQL protocol content and appropriate training and education of trial staff, and (4) that HRQL data collection could be associated with emotional and/or ethical burden. CONCLUSIONS:Our findings suggest there are inconsistencies in the standards of HRQL data collection in some trials resulting from a general lack of HRQL-specific protocol content, training and education. These inconsistencies could lead to biased HRQL trial results. Future research should aim to develop HRQL guidelines and training programmes aimed at supporting researchers to carry out high quality data collection

Patient reported outcomes (PROs) in clinical trials: is 'in-trial' guidance lacking? a systematic review.

BACKGROUND: Patient reported outcomes (PROs) are increasingly assessed in clinical trials, and guidelines are available to inform the design and reporting of such trials. However, researchers involved in PRO data collection report that specific guidance on 'in-trial' activity (recruitment, data collection and data inputting) and the management of 'concerning' PRO data (i.e., data which raises concern for the well-being of the trial participant) appears to be lacking. The purpose of this review was to determine the extent and nature of published guidelines addressing these areas. METHODS AND FINDINGS: Systematic review of 1,362 articles identified 18 eligible papers containing 'in-trial' guidelines. Two independent authors undertook a qualitative content analysis of the selected papers. Guidelines presented in each of the articles were coded according to an a priori defined coding frame, which demonstrated reliability (pooled Kappa 0.86-0.97), and validity (<2% residual category coding). The majority of guidelines present were concerned with 'pre-trial' activities (72%), for example, outcome measure selection and study design issues, or 'post-trial' activities (16%) such as data analysis, reporting and interpretation. 'In-trial' guidelines represented 9.2% of all guidance across the papers reviewed, with content primarily focused on compliance, quality control, proxy assessment and reporting of data collection. There were no guidelines surrounding the management of concerning PRO data. CONCLUSIONS: The findings highlight there are minimal in-trial guidelines in publication regarding PRO data collection and management in clinical trials. No guidance appears to exist for researchers involved with the handling of concerning PRO data. Guidelines are needed, which support researchers to manage all PRO data appropriately and which facilitate unbiased data collection

Outcomes important to patients with non-infectious posterior segment-involving uveitis:a qualitative study

Objective: Uveitis, a group of disorders characterised by intraocular inflammation, causes 10–15% of total blindness in the developed world. The most sight-threatening forms of non-infectious uveitis are those affecting the posterior segment of the eye, collectively known as posterior-segment involving uveitis (PSIU). Numerous different clinical outcomes have been used in trials evaluating treatments for PSIU but these may not represent patients’ and carers’ concerns. Therefore, the aims of this study were to understand the impact of PSIU on adult patients’ and carers’ lives, and to explore what outcomes of treatment are important to them.Methods: Four focus group discussions were undertaken to understand the perspectives of adult patients (n=18) and carers (n=10) with PSIU. Participants were grouped according to whether or not their uveitis was complicated by the sight-threatening condition uveitic macular oedema (UMO). Discussions were audio recorded, transcribed and analysed using the framework analytical approach. Outcomes were identified and grouped into outcome domains. Results: Eleven core domains were identified as important to patients and carers undergoing treatment for PSIU comprising: (1) visual function, (2) symptoms, (3) functional ability, (4) impact on relationships, (5) financial impact, (6) psychological morbidity and emotional well-being (7) psychosocial adjustment to uveitis, (8) doctor/patient/interprofessional relationships and access to health care, (9) treatment burden, (10) treatment side effects, (11) disease control.Conclusion: The domains identified represent patients and carers experience and perspectives and can be used to reflect on outcomes assessed in PSIU. They will directly inform the development of a core outcome set for PSIU clinical trials.Ethical approval: Ethical approval was obtained from the United Kingdom National Research Ethics Service (Reference 17-WM-0111).<br/

Woven Endobridge (WEB) Device as a Re-treatment Strategy after Unsuccessful Surgical Clipping

BACKGROUND: Surgical clipping of intracranial aneurysms is typically robust and durable. However, residual aneurysmal components may be seen after clipping. Furthermore, there may be occasional aneurysmal recurrence. These factors are both clinically relevant because subarachnoid hemorrhage after clipping is a rare but important event. The rationale for any treatment is to substantially decrease the future risk of hemorrhage. Small series have shown coiling as a retreatment strategy after unsuccessful clipping, but none has explored the feasibility of Woven Endobridge (WEB) implantation. CASE DESCRIPTION: We examined the feasibility of WEB implantation as second-line treatment for wide-necked residual aneurysms after unsuccessful clipping. We also recorded the safety and efficacy in this small series of 6 patients. To determine safety, we measured the modified Rankin Scale score before and after the procedure, and at 2 later time points (mean follow-up, 5 months and 15 months). To determine efficacy, we obtained radiographic aneurysm occlusion outcomes (including WEB Occlusion Scale) at these 2 time points. Four middle cerebral artery and 2 anterior communicating artery complex aneurysms were treated with WEB implantation, showing feasibility in 6/6 cases (100%). Follow-up at 15 months showed no change from preprocedural modified Rankin Scale score and there were no other complications. There was adequate occlusion in 5/6 cases (83%). CONCLUSIONS: WEB implantation provided a feasible option in this challenging retreatment scenario. This is a small series and prospective data are required to make outcome inferences for this population. Nonetheless, we observed no complications and high adequate occlusion rates

Large Propulsion Demands Increase Locomotor Adaptation at the Expense of Step Length Symmetry

There is an interest to identify factors facilitating locomotor adaptation induced by split-belt walking (i.e., legs moving at different speeds) because of its clinical potential. We hypothesized that augmenting braking forces, rather than propulsion forces, experienced at the feet would increase locomotor adaptation during and after split-belt walking. To test this, forces were modulated during split-belt walking with distinct slopes: incline (larger propulsion than braking), decline (larger braking than propulsion), and flat (similar propulsion and braking). Step length asymmetry was compared between groups because it is a clinically relevant measure robustly adapted on split-belt treadmills. Unexpectedly, the group with larger propulsion demands (i.e., the incline group) changed their gait the most during adaptation, reached their final adapted state more quickly, and had larger after-effects when the split-belt perturbation was removed. We also found that subjects who experienced larger disruptions of propulsion forces in early adaptation exhibited greater after-effects, which further highlights the catalytic role of propulsion forces on locomotor adaptation. The relevance of mechanical demands on shaping our movements was also indicated by the steady state split-belt behavior, during which each group recovered their baseline leg orientation to meet leg-specific force demands at the expense of step length symmetry. Notably, the flat group was nearly symmetric, whereas the incline and decline group overshot and undershot step length symmetry, respectively. Taken together, our results indicate that forces propelling the body facilitate gait changes during and after split-belt walking. Therefore, the particular propulsion demands to walk on a split-belt treadmill might explain the gait symmetry improvements in hemiparetic gait following split-belt training