Evaluating Quality of Decision-Making Processes in Medicines' Development, Regulatory Review, and Health Technology Assessment : A Systematic Review of the Literature.

Introduction: Although pharmaceutical companies, regulatory authorities, and health technology assessment (HTA) agencies have been increasingly using decision-making frameworks, it is not certain whether these enable better quality decision making. This could be addressed by formally evaluating the quality of decision-making process within those organizations. The aim of this literature review was to identify current techniques (tools, questionnaires, surveys, and studies) for measuring the quality of the decision-making process across the three stakeholders. Methods: Using MEDLINE, Web of Knowledge, and other Internet-based search engines, a literature review was performed to systematically identify techniques for assessing quality of decision making in medicines development, regulatory review, and HTA. A structured search was applied using key words and a secondary review was carried out. In addition, the measurement properties of each technique were assessed and compared. Ten Quality Decision-Making Practices (QDMPs) developed previously were then used as a framework for the evaluation of techniques identified in the review. Due to the variation in studies identified, meta-analysis was inappropriate. Results: This review identified 13 techniques, where 7 were developed specifically to assess decision making in medicines' development, regulatory review, or HTA; 2 examined corporate decision making, and 4 general decision making. Regarding how closely each technique conformed to the 10 QDMPs, the 13 techniques assessed a median of 6 QDMPs, with a mode of 3 QDMPs. Only 2 techniques evaluated all 10 QDMPs, namely the Organizational IQ and the Quality of Decision Making Orientation Scheme (QoDoS), of which only one technique, QoDoS could be applied to assess decision making of both individuals and organizations, and it possessed generalizability to capture issues relevant to companies as well as regulatory authorities. Conclusion: This review confirmed a general paucity of research in this area, particularly regarding the development and systematic application of techniques for evaluating quality decision making, with no consensus around a gold standard. This review has identified QoDoS as the most promising available technique for assessing decision making in the lifecycle of medicines and the next steps would be to further test its validity, sensitivity, and reliability.Peer reviewedFinal Published versio

The use of multiple sclerosis condition-specific measures to inform health policy decision-making: mapping from the MSWS-12 to the EQ-5D

The final version of this paper has been published in Multiple Sclerosis, 18 (6), June 2012 by SAGE Publications Ltd, All rights reserved. © It is available at: http:// msj.sagepub.com/Walking impairment has a major influence on the quality of life of people with multiple sclerosis (MS). The Multiple Sclerosis Walking Scale (MSWS-12) assesses the impact of MS on walking ability from the patient's perspective, but in its current form, is not amenable for use in many policy decision-making settings

What is the evidence for the effectiveness, appropriateness and feasibility of group clinics for patients with chronic conditions? A systematic review

Background Group clinics are a form of delivering specialist-led care in groups rather than in individual consultations. Objective To examine the evidence for the use of group clinics for patients with chronic health conditions. Design A systematic review of evidence from randomised controlled trials (RCTs) supplemented by qualitative studies, cost studies and UK initiatives. Data sources We searched MEDLINE, EMBASE, The Cochrane Library, Web of Science and Cumulative Index to Nursing and Allied Health Literature from 1999 to 2014. Systematic reviews and RCTs were eligible for inclusion. Additional searches were performed to identify qualitative studies, studies reporting costs and evidence specific to UK settings. Review methods Data were extracted for all included systematic reviews, RCTs and qualitative studies using a standardised form. Quality assessment was performed for systematic reviews, RCTs and qualitative studies. UK studies were included regardless of the quality or level of reporting. Tabulation of the extracted data informed a narrative synthesis. We did not attempt to synthesise quantitative data through formal meta-analysis. However, given the predominance of studies of group clinics for diabetes, using common biomedical outcomes, this subset was subject to quantitative analysis. Results Thirteen systematic reviews and 22 RCT studies met the inclusion criteria. These were supplemented by 12 qualitative papers (10 studies), four surveys and eight papers examining costs. Thirteen papers reported on 12 UK initiatives. With 82 papers covering 69 different studies, this constituted the most comprehensive coverage of the evidence base to date. Disease-specific outcomes – the large majority of RCTs examined group clinic approaches to diabetes. Other conditions included hypertension/heart failure and neuromuscular conditions. The most commonly measured outcomes for diabetes were glycated haemoglobin A1c (HbA1c), blood pressure and cholesterol. Group clinic approaches improved HbA1c and improved systolic blood pressure but did not improve low-density lipoprotein cholesterol. A significant effect was found for disease-specific quality of life in a few studies. No other outcome measure showed a consistent effect in favour of group clinics. Recent RCTs largely confirm previous findings. Health services outcomes – the evidence on costs and feasibility was equivocal. No rigorous evaluation of group clinics has been conducted in a UK setting. A good-quality qualitative study from the UK highlighted factors such as the physical space and a flexible appointment system as being important to patients. The views and attitudes of those who dislike group clinic provision are poorly represented. Little attention has been directed at the needs of people from ethnic minorities. The review team identified significant weaknesses in the included research. Potential selection bias limits the generalisability of the results. Many patients who could potentially be included do not consent to the group approach. Attendance is often interpreted liberally. Limitations This telescoped review, conducted within half the time period of a conventional systematic review, sought breadth in covering feasibility, appropriateness and meaningfulness in addition to effectiveness and cost-effectiveness and utilised several rapid-review methods. It focused on the contribution of recently published evidence from RCTs to the existing evidence base. It did not reanalyse trials covered in previous reviews. Following rapid review methods, we did not perform independent double data extraction and quality assessment. Conclusions Although there is consistent and promising evidence for an effect of group clinics for some biomedical measures, this effect does not extend across all outcomes. Much of the evidence was derived from the USA. It is important to engage with UK stakeholders to identify NHS considerations relating to the implementation of group clinic approaches. Future work The review team identified three research priorities: (1) more UK-centred evaluations using rigorous research designs and economic models with robust components; (2) clearer delineation of individual components within different models of group clinic delivery; and (3) clarification of the circumstances under which group clinics present an appropriate alternative to an individual consultation

Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for the treatment of rheumatoid arthritis not previously treated with disease-modifying antirheumatic drugs and after the failure of conventional disease-modifying antirheumatic drugs only: systematic review and economic evaluation.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increasing disability, reduced quality of life and substantial costs (as a result of both intervention acquisition and hospitalisation). The objective was to assess the clinical effectiveness and cost-effectiveness of seven biologic disease-modifying antirheumatic drugs (bDMARDs) compared with each other and conventional disease-modifying antirheumatic drugs (cDMARDs). The decision problem was divided into those patients who were cDMARD naive and those who were cDMARD experienced; whether a patient had severe or moderate to severe disease; and whether or not an individual could tolerate methotrexate (MTX). DATA SOURCES: The following databases were searched: MEDLINE from 1948 to July 2013; EMBASE from 1980 to July 2013; Cochrane Database of Systematic Reviews from 1996 to May 2013; Cochrane Central Register of Controlled Trials from 1898 to May 2013; Health Technology Assessment Database from 1995 to May 2013; Database of Abstracts of Reviews of Effects from 1995 to May 2013; Cumulative Index to Nursing and Allied Health Literature from 1982 to April 2013; and TOXLINE from 1840 to July 2013. Studies were eligible for inclusion if they evaluated the impact of a bDMARD used within licensed indications on an outcome of interest compared against an appropriate comparator in one of the stated population subgroups within a randomised controlled trial (RCT). Outcomes of interest included American College of Rheumatology (ACR) scores and European League Against Rheumatism (EULAR) response. Interrogation of Early Rheumatoid Arthritis Study (ERAS) data was undertaken to assess the Health Assessment Questionnaire (HAQ) progression while on cDMARDs. METHODS: Network meta-analyses (NMAs) were undertaken for patients who were cDMARD naive and for those who were cDMARD experienced. These were undertaken separately for EULAR and ACR data. Sensitivity analyses were undertaken to explore the impact of including RCTs with a small proportion of bDMARD experienced patients and where MTX exposure was deemed insufficient. A mathematical model was constructed to simulate the experiences of hypothetical patients. The model was based on EULAR response as this is commonly used in clinical practice in England. Observational databases, published literature and NMA results were used to populate the model. The outcome measure was cost per quality-adjusted life-year (QALY) gained. RESULTS: Sixty RCTs met the review inclusion criteria for clinical effectiveness, 38 of these trials provided ACR and/or EULAR response data for the NMA. Fourteen additional trials contributed data to sensitivity analyses. There was uncertainty in the relative effectiveness of the interventions. It was not clear whether or not formal ranking of interventions would result in clinically meaningful differences. Results from the analysis of ERAS data indicated that historical assumptions regarding HAQ progression had been pessimistic. The typical incremental cost per QALY of bDMARDs compared with cDMARDs alone for those with severe RA is > £40,000. This increases for those who cannot tolerate MTX (£50,000) and is > £60,000 per QALY when bDMARDs were used prior to cDMARDs. Values for individuals with moderate to severe RA were higher than those with severe RA. Results produced using EULAR and ACR data were similar. The key parameter that affected the results is the assumed HAQ progression while on cDMARDs. When historic assumptions were used typical incremental cost per QALY values fell to £38,000 for those with severe disease who could tolerate MTX. CONCLUSIONS: bDMARDs appear to have cost per QALY values greater than the thresholds stated by the National Institute for Health and Care Excellence for interventions to be cost-effective. Future research priorities include: the evaluation of the long-term HAQ trajectory while on cDMARDs; the relationship between HAQ direct medical costs; and whether or not bDMARDs could be stopped once a patient has achieved a stated target (e.g. remission). STUDY REGISTRATION: This study is registered as PROSPERO CRD42012003386. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Health economic modelling in Cystic Fibrosis:A systematic review

Introduction: Cystic Fibrosis (CF) is a heritable chronic condition. Due to the genetic and progressive nature of CF, a number of interventions are available for the condition. In the United Kingdom (U.K.) average annual cost of CF treatment is between €49,000 to €76,000 (2012) per patient [1]. A review of health economic modelling studies is warranted to provide decision makers and researchers with an in depth understanding of modelling practices in CF and guidance for future research. Methods: Online searches were performed in the 5 databases, studies were included if they were: a) Model based economic evaluation for management of Cystic Fibrosis. Articles were restricted to English language only, but no restriction was applied on publication year. Results: Nine studies were reviewed, most were Markov cohort models. Models evaluated pharmaceutical interventions and drug adherence. Modelling structure was consistent across most articles and a range of sources were used to populate the models. Cost and utility data were based on different sources and elicitation methods respectively. The majority of models failed to incorporate significant health events which impact both cost and disease progression. Conclusion: In our review we observed a lack of, application of European Medicines Agency (EMA) guidelines for clinical trial endpoints, model structure justifications and lastly, health-related quality of life derived utility information around important clinical events. Future work around conceptual modelling of CF progression, utility valuation of significant health events and meeting EMA guidelines for trial reporting is encouraged

Evidence summaries: the evolution of a rapid review approach

<p>Abstract</p> <p>Background</p> <p>Rapid reviews have emerged as a streamlined approach to synthesizing evidence - typically for informing emergent decisions faced by decision makers in health care settings. Although there is growing use of rapid review 'methods', and proliferation of rapid review products, there is a dearth of published literature on rapid review methodology. This paper outlines our experience with rapidly producing, publishing and disseminating evidence summaries in the context of our Knowledge to Action (KTA) research program.</p> <p>Methods</p> <p>The KTA research program is a two-year project designed to develop and assess the impact of a regional knowledge infrastructure that supports evidence-informed decision making by regional managers and stakeholders. As part of this program, we have developed evidence summaries - our form of rapid review - which have come to be a flagship component of this project. Our eight-step approach for producing evidence summaries has been developed iteratively, based on evidence (where available), experience and knowledge user feedback. The aim of our evidence summary approach is to deliver quality evidence that is both timely and user-friendly.</p> <p>Results</p> <p>From November 2009 to March 2011 we have produced 11 evidence summaries on a diverse range of questions identified by our knowledge users. Topic areas have included questions of clinical effectiveness to questions on health systems and/or health services. Knowledge users have reported evidence summaries to be of high value in informing their decisions and initiatives. We continue to experiment with incorporating more of the established methods of systematic reviews, while maintaining our capacity to deliver a final product in a timely manner.</p> <p>Conclusions</p> <p>The evolution of the KTA rapid review evidence summaries has been a positive one. We have developed an approach that appears to be addressing a need by knowledge users for timely, user-friendly, and trustworthy evidence and have transparently reported these methods here for the wider rapid review and scientific community.</p

Pharmacoeconomics of obesity in China: a scoping review

Background: With the growing rate of obesity and associated chronic conditions in China, there is a need to assess the health and economic burdens of obesity and examine the effectiveness of pharmaceutical, medical, and comprehensive weight-loss interventions. Areas covered: This article reviewed publications retrieved from PubMed and Google Scholar during 2010–2020 on pharmacoeconomic studies related to overweight and obesity in China. We identified five cost-of-illness studies and four cost-effectiveness analyses of weight-loss interventions, including bariatric surgeries and a comprehensive intervention program. Expert opinion: There is a lack of pharmacoeconomic analyses of obesity in China. Existing studies have often taken the health system perspective without accounting for productivity loss. Cohort studies and studies based on electronic health records or claims data are needed to provide the epidemiologic parameters required for homegrown economic evaluations of the health and economic burdens of obesity in China, as well as the cost-effectiveness of interventions to reduce obesity and its sequela

Developing a preference-based utility scoring algorithm for the Psoriasis Area Severity Index (PASI)

Introduction It is challenging to identify health state utilities associated with psoriasis because generic preference-based measures may not capture the impact of dermatological symptoms. The Psoriasis Area Severity Index (PASI) is one of the most commonly used psoriasis rating scales in clinical trials. The purpose of this study was to develop a utility scoring algorithm for the PASI. Methods Forty health states were developed based on PASI scores of 40 clinical trial patients. Health states were valued in time trade-off interviews with UK general population participants. Regression models were conducted to crosswalk from PASI scores to utilities (e.g., OLS linear, random effects, mean, robust, spline, quadratic). Results A total of 245 participants completed utility interviews (51.4% female; mean age =45.3y). Models predicting utility based on the four PASI location scores (head, upper limbs, trunk, lower limbs) had better fit/accuracy (e.g., R2, mean absolute error [MAE]) than models using the PASI total score. Head/upper limb scores were more strongly associated with utility than trunk/lower limb. The recommended model is the OLS linear model based on the four PASI location scores (R2 = 0.13; MAE =0.03). An alternative is recommended for situations when it is necessary to estimate utility based on the PASI total score. Conclusions The recommended scoring algorithm may be used to estimate utilities based on PASI scores of any treatment group with psoriasis. Because the PASI is commonly used in psoriasis clinical trials, this scoring algorithm greatly expands options for quantifying treatment outcomes in cost-effectiveness analyses of psoriasis therapies. Results indicate that psoriasis of the head/upper limbs could be more important than trunk/lower limbs, suggesting reconsideration of the standard PASI scoring approach

Effects of an evidence service on community-based AIDS service organizations' use of research evidence: A protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>To support the use of research evidence by community-based organizations (CBOs) we have developed 'Synthesized HIV/AIDS Research Evidence' (SHARE), which is an evidence service for those working in the HIV sector. SHARE consists of several components: an online searchable database of HIV-relevant systematic reviews (retrievable based on a taxonomy of topics related to HIV/AIDS and open text search); periodic email updates; access to user-friendly summaries; and peer relevance assessments. Our objective is to evaluate whether this 'full serve' evidence service increases the use of research evidence by CBOs as compared to a 'self-serve' evidence service.</p> <p>Methods/design</p> <p>We will conduct a two-arm randomized controlled trial (RCT), along with a follow-up qualitative process study to explore the findings in greater depth. All CBOs affiliated with Canadian AIDS Society (n = 120) will be invited to participate and will be randomized to receive either the 'full-serve' version of SHARE or the 'self-serve' version (a listing of relevant systematic reviews with links to records on PubMed and worksheets that help CBOs find and use research evidence) using a simple randomized design. All management and staff from each organization will be provided access to the version of SHARE that their organization is allocated to. The trial duration will be 10 months (two-month baseline period, six-month intervention period, and two month crossover period), the primary outcome measure will be the mean number of logins/month/organization (averaged across the number of users from each organization) between baseline and the end of the intervention period. The secondary outcome will be intention to use research evidence as measured by a survey administered to one key decision maker from each organization. For the qualitative study, one key organizational decision maker from 15 organizations in each trial arm (n = 30) will be purposively sampled. One-on-one semi-structured interviews will be conducted by telephone on their views about and their experiences with the evidence service they received, how helpful it was in their work, why it was helpful (or not helpful), what aspects were most and least helpful and why, and recommendations for next steps.</p> <p>Discussion</p> <p>To our knowledge, this will be the first RCT to evaluate the effects of an evidence service specifically designed to support CBOs in finding and using research evidence.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01257724">NCT01257724</a></p