Rafael Pinedo-Villanueva

Mapping the Oxford hip score onto the EQ-5D utility index.

PurposeTo assess different mapping methods for the estimation of a group’s mean EQ-5D score based on responses to the Oxford hip score (OHS) questionnaire.MethodsFour models were considered: a) linear regression using total OHS as a continuous regressor; b) linear regression employing responses to the twelve OHS questions as categorical predictors; c) two-part approach combining logistic and linear regression; and d) response mapping. The models were internally validated on the estimation data set, which included OHS and EQ-5D scores for total hip replacements, both before and six months after procedure for 1,759 operations. An external validation was also performed.ResultsAll models estimated the mean EQ-5D score within 0.005 of an observed health-state utility estimate, ordinary least squares (OLS) continuous being the most accurate and OLS categorical the most consistent. Age, gender and deprivation did not improve the models. More accurate estimations at the individual level were achieved for higher scores of observed OHS and EQ-5D.ConclusionBased on these results, when EQ-5D scores are not available, answers to the OHS questionnaire can be used to estimate a group’s mean EQ-5D with a high degree of accuracy.

Quantitative assessment of barriers to the clinical development and adoption of cellular therapies: A pilot study.

There has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. We hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products. To investigate this, we launched a pilot study to survey clinicians from five specialities and to determine what they believe to be the most significant barriers to cellular therapy clinical development and adoption. Our study shows that the main concerns among this group are cost-effectiveness, efficacy, reimbursement, and regulation. Addressing these concerns can best be achieved by ensuring that future clinical trials are conducted to adequately answer the questions of both regulators and the broader clinical community.

World Hip Trauma Evaluation (WHiTE): framework for embedded comprehensive cohort studies

Introduction Osteoporotic hip fractures present a significant global challenge to patients, clinicians and healthcare systems. It is estimated that hip fracture accounts for 1.4% of total social and healthcare costs in the established market economies. Methods and analysis The World Hip Trauma Evaluation (WHiTE) was set up to measure outcome in a comprehensive cohort of UK patients with hip fracture. All patients in the cohort are treated under a single comprehensive treatment pathway. A core outcome set, including health-related quality of life, is collected on all the patients. This protocol describes the current multicentre project that will be used as a vehicle to deliver a series of embedded observational studies. Ethics and dissemination Research Ethics Committee approval was granted (Rec reference 11/LO/0927, approved 18/8/2011) and each hospital trust provided National Health Service (NHS) approvals. Trial registration number The study is registered with National Institute of Health Research Portfolio (UKCRN ID 12351) and the ISRCTN registry (ISRCTN63982700).

Health-related quality of life and a cost-utility simulation of adults in the UK with osteogenesis imperfecta, X-linked hypophosphatemia and fibrous dysplasia.

BackgroundHealth-related quality of life of adults with osteogenesis imperfecta (OI), fibrous dysplasia (FD) and X-linked hypophosphatemia (XLH) remains poorly described. The aim of this study was to describe the HRQoL of adults with osteogenesis imperfecta, fibrous dysplasia and X-linked hypophophataemia and perform a cost-utility simulation to calculate the maximum cost that a health care system would be willing to pay for a hypothetical treatment of a rare bone disease.ResultsParticipants completed the EQ-5D-5 L questionnaire between September 2014 and March 2016. For the economic simulation, we considered a hypothetical treatment that would be applied to OI participants in the lower tertile of the health utility score.A total of 109 study participants fully completed the EQ-5D-5 L questionnaire (response rate 63%). Pain/discomfort was the most problematic domain for participants with all three diseases (FD 31%, XLH 25%, OI 16%).The economic simulation identified an expected treatment impact of +2.5 QALYs gained per person during the 10-year period, which led to a willing to pay of £14,355 annually for a health care system willing to pay up to £50,000 for each additional QALY gained by an intervention.ConclusionsThis is the first study to quantitatively measure and compare the HRQoL of adults with OI, FD and XLH and the first to use such data to conduct an economic simulation leading to healthcare system willingness-to-pay estimates for treatment of musculoskeletal rare diseases at various cost-effectiveness thresholds.

The implementation of novel collaborative structures for the identification and resolution of barriers to pluripotent stem cell translation.

Increased global connectivity has catalyzed technological development in almost all industries, in part through the facilitation of novel collaborative structures. Notably, open innovation and crowd-sourcing-of expertise and/or funding-has tremendous potential to increase the efficiency with which biomedical ecosystems interact to deliver safe, efficacious and affordable therapies to patients. Consequently, such practices offer tremendous potential in advancing development of cellular therapies. In this vein, the CASMI Translational Stem Cell Consortium (CTSCC) was formed to unite global thought-leaders, producing academically rigorous and commercially practicable solutions to a range of challenges in pluripotent stem cell translation. Critically, the CTSCC research agenda is defined through continuous consultation with its international funding and research partners. Herein, initial findings for all research focus areas are presented to inform global product development strategies, and to stimulate continued industry interaction around biomanufacturing, strategic partnerships, standards, regulation and intellectual property and clinical adoption.

Choosing Between Unicompartmental and Total Knee Replacement: What Can Economic Evaluations Tell Us? A Systematic Review

Background and objectivePatients with anteromedial arthritis who require a knee replacement could receive either a unicompartmental knee replacement (UKR) or a total knee replacement (TKR). This review has been undertaken to identify economic evaluations comparing UKR and TKR, evaluate the approaches that were taken in the studies, assess the quality of reporting of these evaluations, and consider what they can tell us about the relative value for money of the procedures.MethodsA search of MEDLINE, EMBASE and the Centre for Reviews and Dissemination National Health Service Economic Evaluation Database was undertaken in January 2016 to identify relevant studies. Study characteristics were described, the quality of reporting and methods assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist, and study findings summarised.ResultsTwelve studies satisfied the inclusion criteria. Five were within-study analyses, while another was based on a literature review. The remaining six studies were model-based analyses. All studies were informed by observational data. While methodological approaches varied, studies generally had either limited follow-up, did not fully account for baseline differences in patient characteristics or relied on previous research that did not. The quality of reporting was generally adequate across studies, except for considerations of the settings to which evaluations applied and the generalisability of the results to other decision-making contexts. In the short-term, UKR was generally associated with better health outcomes and lower costs than TKR. Initial cost savings associated with UKR seem to persist over patients’ lifetimes even after accounting for higher rates of revision. For older patients, initial health improvements also appear to be maintained, making UKR the dominant treatment choice. However, for younger patients findings for health outcomes and overall cost effectiveness are mixed, with the difference in health outcomes depending on the lifetime risk of revision and patient outcomes following revision.ConclusionsUKR appears to be less costly than TKR. For older patients, UKR is also expected to lead to better health outcomes, making it the dominant choice; however, for younger patients health outcomes are more uncertain. Future research should better account for baseline differences in patient characteristics and consider how the relative value of UKR and TKR varies depending on patient and surgical factors.

An Unsupervised Learning Model for Pattern Recognition in Routinely Collected Healthcare Data

This study examines a large routinely collected healthcare database containing patient-level self-reported outcomes following knee replacement surgery. A model based on unsupervised machine learning methods, including k-means and hierarchical clustering, is proposed to detect patterns of pain experienced by patients and to derive subgroups of patients with different outcomes based on their pain characteristics. Results showed the presence of between two and four different sub-groups of patients based on their pain characteristics. Challenges associated with unsupervised learning using real-world data are described and an approach for evaluating models in the presence of unlabelled data using internal and external cluster evaluation techniques is presented, that can be extended to other unsupervised learning applications within healthcare and beyond. To our knowledge, this is the first study proposing an unsupervised learning model for characterising painbased patient subgroups using the UK NHS PROMs database.

Trends and determinants of length of stay and hospital reimbursement following knee and hip replacement: evidence from linked primary care and NHS hospital records from 1997 to 2014.

Objectives To measure changes in length of stay following total knee and hip replacement (TKR and THR) between 1997 and 2014 and estimate the impact on hospital reimbursement, all else being equal. Further, to assess the degree to which observed trends can be explained by improved efficiency or changes in patient profiles. Design Cross-sectional study using routinely collected data. Setting National Health Service primary care records from 1995 to 2014 in the Clinical Practice Research Datalink were linked to hospital inpatient data from 1997 to 2014 in Hospital Episode Statistics Admitted Patient Care. Participants Study participants had a diagnosis of osteoarthritis or rheumatoid arthritis. Interventions Primary TKR, primary THR, revision TKR and revision THR. Primary outcome measures Length of stay and hospital reimbursement. Results 10 260 primary TKR, 10 961 primary THR, 505 revision TKR and 633 revision THR were included. Expected length of stay fell from 16.0 days (95% CI 14.9 to 17.2) in 1997 to 5.4 (5.2 to 5.6) in 2014 for primary TKR and from 14.4 (13.7 to 15.0) to 5.6 (5.4 to 5.8) for primary THR, leading to savings of £1537 and £1412, respectively. Length of stay fell from 29.8 (17.5 to 50.5) to 11.0 (8.3 to 14.6) for revision TKR and from 18.3 (11.6 to 28.9) to 12.5 (9.3 to 16.8) for revision THR, but no significant reduction in reimbursement was estimated. The estimated effect of year of surgery remained similar when patient characteristics were included. Conclusions Length of stay for joint replacement fell substantially from 1997 to 2014. These reductions have translated into substantial savings. While patient characteristics affect length of stay and reimbursement, patient profiles have remained broadly stable over time. The observed reductions appear to be mostly explained by improved efficiency.

A quantitative, multi-national and multi-stakeholder assessment of barriers to the adoption of cell therapies

Cellular therapies, such as stem cell–based treatments, have been widely researched and numerous products and treatments have been developed. Despite this, there has been relatively limited use of these technologies in the healthcare sector. This study sought to investigate the perceived barriers to this more widespread adoption. An anonymous online questionnaire was developed, based on the findings of a pilot study. This was distributed to an audience of clinicians, researchers and commercial experts in 13 countries. The results were analysed for all respondents, and also sub-grouped by geographical region, and by profession of respondents. The results of the study showed that the most significant barrier was manufacturing, with other factors such as efficacy, regulation and cost-effectiveness being identified by the different groups. This study further demonstrates the need for these important issues to be addressed during the development of cellular therapies to enable more widespread adoption of these treatments.

Evidence for current recommendations concerning the management of foot health for people with chronic long-term conditions: a systematic review

BackgroundResearch focusing on management of foot health has become more evident over the past decade, especially related to chronic conditions such as diabetes. The level of methodological rigour across this body of work however is varied and outputs do not appear to have been developed or translated into clinical practice. The aim of this systematic review was to assess the latest guidelines, standards of care and current recommendations relative to people with chronic conditions to ascertain the level of supporting evidence concerning the management of foot health.MethodsA systematic search of electronic databases (Medline, Embase, Cinahl, Web of Science, SCOPUS and The Cochrane Library) for literature on recommendations for foot health management for people with chronic conditions was performed between 2000 and 2016 using predefined criteria. Data from the included publications was synthesised via template analysis, employing a thematic organisation and structure. The methodological quality of all included publications was appraised using the Appraisal for Research and Evaluation (AGREE II) instrument. A more in-depth analysis was carried out that specifically considered the levels of evidence that underpinned the strength of their recommendations concerning management of foot health.ResultsThe data collected revealed 166 publications in which the majority (102) were guidelines, standards of care or recommendations related to the treatment and management of diabetes. We noted a trend towards a systematic year on year increase in guidelines standards of care or recommendations related to the treatment and management of long term conditions other than diabetes over the past decade. The most common recommendation is for preventive care or assessments (e.g. vascular tests), followed by clinical interventions such as foot orthoses, foot ulcer care and foot health education. Methodological quality was spread across the range of AGREE II scores with 62 publications falling into the category of high quality (scores 6–7). The number of publications providing a recommendation in the context of a narrative but without an indication of the strength or quality of the underlying evidence was high (79 out of 166).ConclusionsIt is clear that evidence needs to be accelerated and in place to support the future of the Podiatry workforce. Whilst high level evidence for podiatry is currently low in quantity, the methodological quality is growing. Where levels of evidence have been given in in high quality guidelines, standards of care or recommendations, they also tend to be strong-moderate quality such that further strategically prioritised research, if performed, is likely to have an important impact in the field.