GRADE Concept 7: Issues and Insights Linking Guideline Recommendations to Trustworthy Essential Medicine Lists.

OBJECTIVES: Guidelines and essential medicine lists (EMLs) bear similarities and differences in the process that lead to decisions. Access to essential medicines is central to achieve universal health coverage. The World Health Organization (WHO) EML has guided prioritization of essential medicines globally for nearly 50 years, and national EMLs (NEMLs) exist in over 130 countries. Guideline and EML decisions, at WHO or national levels, are not always coordinated and aligned. We sought to explore challenges, and potential solutions, for decision-making to support trustworthy medicine selection for EMLs from a Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Working Group perspective. We primarily focus on the WHO EML; however, our findings may be applicable to NEML decisions as well. STUDY DESIGN AND SETTING: We identified key challenges in connecting the EML to health guidelines by involving a broad group of stakeholders and assessing case studies including real applications to the WHO EML, South Africa NEML, and a multiple sclerosis guideline connected to a WHO EML application for multiple sclerosis treatments. To address challenges, we utilized the results of a survey and feedback from the stakeholders, and iteratively met as a project group. We drafted a conceptual framework of challenges and potential solutions. We presented a summary of the results for feedback to all attendees of the GRADE Working Group meetings in November 2022 (approximately 120 people) and in May 2023 (approximately 100 people) before finalizing the framework. RESULTS: We prioritized issues and insights/solutions that addressed the connections between the EML and health guidelines. Our suggested solutions include early planning alignment of guideline groups and EMLs, considering shared participation to strengthen linkage, further clarity on price/cost considerations, and using explicit shared criteria to make guideline and EML decisions. We also provide recommendations to strengthen the connection between WHO EML and NEMLs including through contextualization methods. CONCLUSION: This GRADE concept article, jointly developed by key stakeholders from the guidelines and EMLs field, identified key conceptual issues and potential solutions to support the continued advancement of trustworthy EMLs. Adopting structured decision criteria that can be linked to guideline recommendations bears the potential to advance health equity and gaps in availability of essential medicines within and between countries.

Cancer Medicines: What Is Essential and Affordable in India?

PURPOSE: The WHO essential medicines list (EML) guides selection of drugs for national formularies. Here, we evaluate which medicines are considered highest priority by Indian oncologists and the extent to which they are available in routine practice. METHODS: This is a secondary analysis of an electronic survey developed by the WHO EML Cancer Medicine Working Group. The survey was distributed globally using a hierarchical snowball method to physicians who prescribe systemic anticancer therapy. The survey captured the 10 medicines oncologists considered highest priority for population health and their availability in routine practice. RESULTS: The global study cohort included 948 respondents from 82 countries; 98 were from India and 67 were from other low- and middle-income countries. Compared with other low- and middle-income countries, the Indian cohort was more likely to be medical oncologist (70% v 31%, P < .001) and work exclusively in the private health system (52% v 17%, P < .001). 14/20 most commonly selected medicines were conventional cytotoxic drugs. Universal access to these medicines was reported by a minority of oncologists; risks of significant out-of-pocket expenditures for each medicine were reported by 19%-58% of oncologists. Risk of catastrophic expenditure was reported by 58%-67% of oncologists for rituximab and trastuzumab. Risks of financial toxicity were substantially higher within the private health system compared with the public system. CONCLUSION: Most high-priority cancer medicines identified by Indian oncologists are generic chemotherapy agents that provide substantial improvements in survival and are already included in WHO EML. Access to these treatments remains limited by major financial burdens experienced by patients. This is particularly acute within the private health system. Strategies are urgently needed to ensure that high-quality cancer care is affordable and accessible to all patients in India.

The ecosystem of health decision making: from fragmentation to synergy.

Clinicians, patients, policy makers, funders, programme managers, regulators, and science communities invest considerable amounts of time and energy in influencing or making decisions at various levels, using systematic reviews, health technology assessments, guideline recommendations, coverage decisions, selection of essential medicines and diagnostics, quality assurance and improvement schemes, and policy and evidence briefs. The criteria and methods that these actors use in their work differ (eg, the role economic analysis has in decision making), but these methods frequently overlap and exist together. Under the aegis of WHO, we have brought together representatives of different areas to reconcile how the evidence that influences decisions is used across multiple health system decision levels. We describe the overlap and differences in decision-making criteria between different actors in the health sector to provide bridging opportunities through a unifying broad framework that we call theory of everything. Although decision-making activities respond to system needs, processes are often poorly coordinated, both globally and on a country level. A decision made in isolation from other decisions on the same topic could cause misleading, unnecessary, or conflicted inputs to the health system and, therefore, confusion and resource waste.

Access to cancer medicines deemed essential by oncologists in 82 countries: an international, cross-sectional survey.

BACKGROUND: The WHO Essential Medicines List (EML) identifies priority medicines that are most important to public health. Over time, the EML has included an increasing number of cancer medicines. We aimed to investigate whether the cancer medicines in the EML are aligned with the priority medicines of frontline oncologists worldwide, and the extent to which these medicines are accessible in routine clinical practice. METHODS: This international, cross-sectional survey was developed by investigators from a range of clinical practice settings across low-income to high-income countries, including members of the WHO Essential Medicines Cancer Working Group. A 28-question electronic survey was developed and disseminated to a global network of oncologists in 89 countries and regions by use of a hierarchical snowball method; each primary contact distributed the survey through their national and regional oncology associations or personal networks. The survey was open from Oct 15 to Dec 7, 2020. Fully qualified physicians who prescribe systemic anticancer therapy to adults were eligible to participate in the survey. The primary question asked respondents to select the ten cancer medicines that would provide the greatest public health benefit to their country; subsequent questions explored availability and cost of cancer medicines. Descriptive statistics were used to compare access to medicines between low-income and lower-middle-income countries, upper-middle-income countries, and high-income countries. FINDINGS: 87 country-level contacts and two regional networks were invited to participate in the survey; 46 (52%) accepted the invitation and distributed the survey. 1697 respondents opened the survey link; 423 were excluded as they did not answer the primary study question and 326 were excluded because of ineligibility. 948 eligible oncologists from 82 countries completed the survey (165 [17%] in low-income and lower-middle-income countries, 165 [17%] in upper-middle-income countries, and 618 [65%] in high-income countries). The most commonly selected medicines were doxorubicin (by 499 [53%] of 948 respondents), cisplatin (by 470 [50%]), paclitaxel (by 423 [45%]), pembrolizumab (by 414 [44%]), trastuzumab (by 402 [42%]), carboplatin (by 390 [41%]), and 5-fluorouracil (by 386 [41%]). Of the 20 most frequently selected high-priority cancer medicines, 19 (95%) are currently on the WHO EML; 12 (60%) were cytotoxic agents and 13 (65%) were granted US Food and Drug Administration regulatory approval before 2000. The proportion of respondents indicating universal availability of each top 20 medication was 9-54% in low-income and lower-middle-income countries, 13-90% in upper-middle-income countries, and 68-94% in high-income countries. The risk of catastrophic expenditure (spending >40% of total consumption net of spending on food) was more common in low-income and lower-middle-income countries, with 13-68% of respondents indicating a substantial risk of catastrophic expenditures for each of the top 20 medications in lower-middle-income countries versus 2-41% of respondents in upper-middle-income countries and 0-9% in high-income countries. INTERPRETATION: These data demonstrate major barriers in access to core cancer medicines worldwide. These findings challenge the feasibility of adding additional expensive cancer medicines to the EML. There is an urgent need for global and country-level policy action to ensure patients with cancer globally have access to high priority medicines. FUNDING: None.

Global access to affordable direct oral anticoagulants.

Poor control of cardiovascular disease accounts for a substantial proportion of the disease burden in developing countries, but often essential anticoagulant medicines for preventing strokes and embolisms are not widely available. In 2019, direct oral anticoagulants were added to the World Health Organization's WHO Model list of essential medicines. The aims of this paper are to summarize the benefits of direct oral anticoagulants for patients with cardiovascular disease and to discuss ways of increasing their usage internationally. Although the cost of direct oral anticoagulants has provoked debate, the affordability of introducing these drugs into clinical practice could be increased by: price negotiation; pooled procurement; competitive tendering; the use of patent pools; and expanded use of generics. In 2017, only 14 of 137 countries that had adopted national essential medicines lists included a direct oral anticoagulant on their lists. This number could increase rapidly if problems with availability and affordability can be tackled. Once the types of patient likely to benefit from direct oral anticoagulants have been clearly defined in clinical practice guidelines, coverage can be more accurately determined and associated costs can be better managed. Government action is required to ensure that direct oral anticoagulants are covered by national budgets because the absence of reimbursement remains an impediment to achieving universal coverage. Tackling cardiovascular disease with the aid of direct oral anticoagulants is an essential component of efforts to achieve the World Health Organization's target of reducing premature deaths due to noncommunicable disease by 25% by 2025.

L'absence de lutte efficace contre les maladies cardiovasculaires contribue grandement à la charge de morbidité pesant sur les pays en développement. Pourtant, les anticoagulants essentiels permettant d'éviter les accidents vasculaires cérébraux et les embolies sont souvent difficiles à obtenir. En 2019, les anticoagulants oraux directs ont été ajoutés à la Liste modèle des médicaments essentiels publiée par l'Organisation mondiale de la Santé. Le présent document vise à résumer les avantages des anticoagulants oraux directs pour les patients souffrant d'une maladie cardiovasculaire, et à évoquer les moyens d'encourager leur utilisation au niveau international. Bien que le coût des anticoagulants oraux directs ait fait débat, intégrer ces médicaments dans la pratique clinique les rendrait plus abordables grâce à diverses méthodes: négociation des prix; achats groupés; appels d'offres concurrentiels; communautés de brevets; et recours accru aux alternatives génériques. En 2017, seulement 14 des 137 pays ayant adopté des listes nationales de médicaments essentiels y avaient inclus des anticoagulants oraux directs. Ce chiffre pourrait augmenter rapidement si les problèmes de disponibilité et d'accessibilité peuvent être résolus. Dès que les profils des patients susceptibles d'être traités par des anticoagulants oraux directs sont clairement établis dans les directives de pratique clinique, la couverture peut être définie avec plus de précision et les dépenses correspondantes, mieux gérées. Les gouvernements doivent s'assurer que ces médicaments sont bien pris en compte dans les budgets nationaux, car l'absence de remboursement demeure un obstacle à la couverture maladie universelle. La lutte contre les maladies cardiovasculaires à l'aide des anticoagulants oraux directs est un élément essentiel des efforts destinés à atteindre l'objectif de l'OMS: faire baisser de 25% d'ici 2025 les décès prématurés dus aux maladies non transmissibles de 25% d'ici 2025.

El mal control de las enfermedades cardiovasculares representa una proporción importante de la carga de enfermedades en los países en desarrollo, y a menudo los medicamentos anticoagulantes esenciales para prevenir los accidentes cerebrovasculares y las embolias no son fácilmente accesibles. En 2019, los anticoagulantes orales directos se añadieron a la lista modelo de medicamentos esenciales de la Organización Mundial de la Salud. Los objetivos del presente artículo son resumir los beneficios de los anticoagulantes orales directos para los pacientes con enfermedades cardiovasculares y discutir las formas de aumentar su uso a nivel internacional. Aunque el coste de los anticoagulantes orales directos ha suscitado debate, la asequibilidad de introducir estos medicamentos en la práctica clínica podría aumentarse al: negociar precios; hacer adquisiciones conjuntas; hacer licitaciones competitivas; utilizar consorcios de patentes; y ampliar el uso de genéricos. En 2017, solo 14 de los 137 países que habían adoptado listas nacionales de medicamentos esenciales incluían un anticoagulante oral directo en sus listas. Este número podría aumentar rápidamente si se pueden abordar los problemas de disponibilidad y asequibilidad. Cuando los tipos de pacientes que pueden beneficiarse de los anticoagulantes orales directos se hayan definido claramente en las directrices de la práctica clínica, la cobertura podrá determinarse con mayor precisión y los costes asociados podrán gestionarse mejor. Es necesario que los gobiernos actúen para garantizar que los anticoagulantes orales directos estén cubiertos por los presupuestos nacionales, ya que la ausencia de reembolso sigue siendo un impedimento para lograr la cobertura universal. La lucha contra las enfermedades cardiovasculares con la ayuda de los anticoagulantes orales directos es un componente esencial de los esfuerzos por alcanzar el objetivo de la OMS de reducir las muertes prematuras debidas a enfermedades no transmisibles en un 25 % para 2025.

Reimbursement models to tackle market failures for antimicrobials: Approaches taken in France, Germany, Sweden, the United Kingdom, and the United States.

INTRODUCTION: The pipeline of new antibacterials remains limited. Reasons include low research investments, limited commercial prospects, and scientific challenges. To complement existing initiatives such as research grants, governments are exploring policy options for providing new market incentives to drug developers. MATERIALS AND METHODS: Reimbursement interventions for antibacterials in France, Germany, Sweden, US, and UK were reviewed and analysed by the authors. RESULTS: In France, Germany, and the US, implemented interventions centre on providing exceptions in cost-containment mechanisms to allow higher prices for certain antibacterials. In the US, also, certain antibacterials are granted additional years of protection from generic competition (exclusivity) and faster regulatory review. The UK is piloting a model that will negotiate contracts with manufacturers to pay a fixed annual fee for ongoing supply of as many units as needed. Sweden is piloting a model that will offer manufacturers of selected antibacterials contracts that would guarantee a minimum annual revenue. A similar model of guaranteed minimal annual revenues is under consideration in the US (PASTEUR Act). CONCLUSIONS: The UK and Sweden are piloting entirely novel procurement and reimbursement models. Existing interventions in the US, France, and Germany represent important, but relatively minor interventions. More countries should explore the use of novel models and international coordination will be important for 'pull' incentives to be effective. If adopted, the PASTEUR legislation in the US would constitute a significant 'pull' incentive.

Diagnostic test accuracy of an automated device as a screening tool for fall risk assessment in community-residing elderly: A STARD compliant study.

We aimed to determine the accuracy and failure of OAK device, an automated screening, for the assessment of fall risk in a prospective cohort of healthy adults aged over 65 years. The algorithm for fall risk assessment of the centers for disease control and prevention (CDC) was used as reference standard. Of the 183 individuals recruited, the CDC algorithm classified 80 as being at moderate/high risk and 103 at low risk of falling. OAK device failure incidence was 4.9% (confidence interval [CI] upper limit 7.7%), below the preset threshold for futility-early termination of the study (i.e., not above 15%). The OAK device showed a sensitivity of 84% and a specificity of 67% (receiver operating characteristic [ROC] area 82%; 95% confidence interval [CI] 76-88%), not reaching the preplanned target sensitivity (not lower than 85%). Diagnostic accuracy was not far from the sensitivity levels similar to those obtained with other fall risk assessment. However, some limitations can be considered.ClinicalTrials.gov identifier: NCT02655796.

Comparison of essential medicines lists in 137 countries.

OBJECTIVE: To compare the medicines included in national essential medicines lists with the World Health Organization's (WHO's) Model list of essential medicines, and assess the extent to which countries' characteristics, such as WHO region, size and health care expenditure, account for the differences. METHODS: We searched the WHO's Essential Medicines and Health Products Information Portal for national essential medicines lists. We compared each national list of essential medicines with both the 2017 WHO model list and other national lists. We used linear regression to determine whether differences were dependent on WHO Region, population size, life expectancy, infant mortality, gross domestic product and health-care expenditure. FINDINGS: We identified 137 national lists of essential medicines that collectively included 2068 unique medicines. Each national list contained between 44 and 983 medicines (median 310: interquartile range, IQR: 269 to 422). The number of differences between each country's essential medicines list and WHO's model list ranged from 93 to 815 (median: 296; IQR: 265 to 381). Linear regression showed that only WHO region and health-care expenditure were significantly associated with the number of differences (adjusted R2 : 0.33; P < 0.05). Most medicines (1248; 60%) were listed by no more than 10% (14) of countries. CONCLUSION: The substantial differences between national lists of essential medicines are only partly explained by differences in country characteristics and thus may not be related to different priority needs. This information helps to identify opportunities to improve essential medicines lists.

GRADE equity guidelines 4: considering health equity in GRADE guideline development: evidence to decision process.

OBJECTIVES: The aim of this paper is to provide detailed guidance on how to incorporate health equity within the GRADE (Grading Recommendations Assessment and Development Evidence) evidence to decision process. STUDY DESIGN AND SETTING: We developed this guidance based on the GRADE evidence to decision framework, iteratively reviewing and modifying draft documents, in person discussion of project group members and input from other GRADE members. RESULTS: Considering the impact on health equity may be required, both in general guidelines and guidelines that focus on disadvantaged populations. We suggest two approaches to incorporate equity considerations: (1) assessing the potential impact of interventions on equity and (2) incorporating equity considerations when judging or weighing each of the evidence to decision criteria. We provide guidance and include illustrative examples. CONCLUSION: Guideline panels should consider the impact of recommendations on health equity with attention to remote and underserviced settings and disadvantaged populations. Guideline panels may wish to incorporate equity judgments across the evidence to decision framework. This is the fourth and final paper in a series about considering equity in the GRADE guideline development process. This series is coming from the GRADE equity subgroup.

Agreements between Industry and Academia on Publication Rights: A Retrospective Study of Protocols and Publications of Randomized Clinical Trials.

BACKGROUND: Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees. METHODS AND FINDINGS: We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner's right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements. CONCLUSIONS: Publication agreements constraining academic authors' independence are common. Journal articles seldom report on publication agreements, and, if they do, statements can be discrepant with the trial protocol.

Improving Power and Sample Size Calculation in Rehabilitation Trial Reports: A Methodological Assessment.

OBJECTIVE: To systematically assess the reporting of sample size calculation in randomized controlled trials (RCTs) on rehabilitation interventions for mechanical low back pain. DATA SOURCES: The Cochrane Database of Systematic Reviews was searched through February 2015. STUDY SELECTION: We conducted an electronic database search for RCTs published from January 1, 1968 to February 28, 2015 and included in the Cochrane Systematic Reviews. DATA EXTRACTION: Two investigators independently used an ad hoc 6-item checklist derived from the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement recommendations to extract data on sample size calculation. The primary outcome was the proportion of RCTs that reported sample size calculation; the secondary outcome was the completeness of sample size analysis reporting. We also evaluated improvement in reporting of sample size calculation over time. DATA SYNTHESIS: Sample size calculation was reported in 80 (36.0%) of the 222 eligible RCTs included in 14 Cochrane Systematic Reviews. Only 13 (16.3%) of these RCT reports gave a complete description, and about half reported ≥4 of the 6 elements of sample size calculation (median, 4; interquartile range, 3-5). Completeness of reporting of sample size calculation improved from 1968 to 2013; since 2005, the number of RCTs reporting sample size calculation has increased compared with the number of RCTs not reporting it. CONCLUSIONS: Despite improvement, reporting of sample size calculation and power analysis remains inadequate, limiting the reader's ability to assess the quality and accuracy of rehabilitation studies.

[Decisional framework for varicella vaccine: challenges in the face of opportunity]. / Modello decisionale per l'adozione del vaccino antivaricella: una sfida di fattibilità.

INTRODUCTION: Decision makers adopt interventions, including vaccines, which are most beneficial to populations. A transparent, unbiased, and comprehensive framework based on evidence-based criteria is a promising tool to guide decision-making on vaccine adoption: we developed a multi-dimensional framework conceived from the DECIDE - Evidence to decision Framework (EtD framework). We validated the framework by conducting a real data and evidence set collection on varicella vaccination and tested it with a multidisciplinary group. METHODS: The EtD framework presented evidence concerning the varicella vaccination organized in six dimensions: Burden of disease, Vaccine characteristics and impact of immunization program, Values and preferences, Resource use, Equity and Feasibility. Two reviewers completed each dimension with information about varicella vaccine. A multidisciplinary group of 42 participants were asked to evaluate the information in the framework, decide whether to introduce varicella vaccine in the national immunization program, assess the usefulness, and propose some impovements of the decision-making tool. RESULTS: From 33 responders (79%) out of 42, 61% supported the adoption of the varicella vaccine as part of the national immunization program. A half (50%) favored the monovalent vaccine while the other half chose the tetravalent vaccine. About 90% of responders found information in the EtD framework comprehensive, easy to understand, and presented in a way that helped make decisions. CONCLUSIONS: Complete and transparent information are welcome. The EtD identified a situation of important divergences between policy makers regarding the introduction and the choice of vaccine. In our case study, for example, a third of the multidisciplinary group did not recommend the adoption of varicella vaccine.

Development of Red Flags Index for Early Referral of Adults with Symptoms and Signs Suggestive of Crohn's Disease: An IOIBD Initiative.

BACKGROUND AND AIMS: Diagnostic delay is frequent in patients with Crohn's disease (CD). We developed a tool to predict early diagnosis. METHODS: A systematic literature review and 12 CD specialists identified 'Red Flags', i.e. symptoms or signs suggestive of CD. A 21-item questionnaire was administered to 36 healthy subjects, 80 patients with irritable bowel syndrome (non-CD group) and 85 patients with recently diagnosed (<18 months) CD. Patients with CD were asked to recall symptoms and signs they experienced during the 12 months before diagnosis. Multiple logistic regression analyses selected and weighted independent items to construct the Red Flags index. A receiver operating characteristic curve was used to assess the threshold that discriminated CD from non-CD. Association with the Red Flags index relative to this threshold was expressed as the odds ratios (OR). RESULTS: Two hundred and one subjects, CD and non-CD, answered the questionnaire. The multivariate analysis identified eight items independently associated with a diagnosis of CD. A minimum Red Flags index value of 8 was highly predictive of CD diagnosis with sensitivity and specificity bootstrap estimates of 0.94 (95% confidence interval 0.88-0.99) and 0.94 (0.90-0.97), respectively. Positive and negative likelihood ratios were 15.1 (9.3-33.6) and 0.066 (0.013-0.125), respectively. The association between CD diagnosis and a Red Flags index value of ≥8 corresponds to an OR of 290 (p < 0.0001). CONCLUSIONS: The Red Flags index using early symptoms and signs has high predictive value for the diagnosis of CD. These results need prospective validation prior to introduction into clinical practice.

Exploring the practice of patient centered care: The role of ethnography and reflexivity.

Patient centered care (PCC) is an essential dimension of healthcare systems' mission worldwide and is recognized as an important condition for ensuring the quality of care. Nonetheless, it is also acknowledged that various care providers perceive patient centeredness differently and that there remain several unanswered questions about the aspects of healthcare delivery that are linked to an actual achievement of PCC. In the paper, we categorize the current research on PCC into two streams ("dyadic" and "organizational") and we discuss the strengths and weaknesses of each. Despite their important contributions to healthcare services research, these approaches to PCC do not fully capture the network of practices and relationships constituting patients and providers' experiences within healthcare contexts. Therefore, we propose an alternative interpretation of PCC that integrates insights from "practice theories" and emphasizes the negotiated and local nature of patient centeredness, which is accomplished through the engagement of providers and patients in everyday care practices. To develop such interpretation, we propose a research approach combining ethnographic and reflexive methods. Ethnography can help achieve more nuanced descriptions of what PCC truly encapsulates in the care process by drawing attention to the social and material reality of healthcare contexts. Reflexivity can help disentangle and bring to surface the tacit knowledge spread in everyday care practices and transform it into actionable knowledge, a type of knowledge that may support services improvement toward PCC. We anticipate that such improvement is far from straightforward: an actual achievement of PCC may challenge the interests of different stakeholders and unsettle consolidated habits, hierarchies and power dynamics. This unsettlement, however, can also serve as a necessary condition for engaging in a participative process of internal development. We discuss the outcomes, limitations and benefits of our approach through a hospital case study.

Prevalence, characteristics, and publication of discontinued randomized trials.

IMPORTANCE: The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear. OBJECTIVES: To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication. DESIGN AND SETTING: Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013. MAIN OUTCOMES AND MEASURES: Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys. RESULTS: After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% [95% CI, 22.3%-27.6%]). Only 96 of 253 discontinuations (37.9% [95% CI, 32.0%-44.3%]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9% [95% CI, 8.2%-12.0%]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio [OR], 0.25 [95% CI, 0.15-0.43]; P < .001) and a larger planned sample size in increments of 100 (-0.7%; OR, 0.96 [95% CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95% CI, 2.29-4.43]; P < .001). CONCLUSIONS AND RELEVANCE: In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials.

Survey of the reporting characteristics of systematic reviews in rehabilitation.

BACKGROUND: Systematic reviews (SRs) have become increasingly important for informing clinical practice; however, little is known about the reporting characteristics and the quality of the SRs relevant to the practice of rehabilitation health professionals. OBJECTIVE: The purpose of this study was to examine the reporting quality of a representative sample of published SRs on rehabilitation, focusing on the descriptive, reporting, and bias-related characteristics. METHODS: A cross-sectional study was conducted by searching MEDLINE for aggregative and configurative SRs indexed in 2011 that focused on rehabilitation as restorative of functional limitations. Two reviewers independently screened and selected the SRs and extracted data using a 38-item data collection form derived from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The data were analyzed descriptively. RESULTS: Eighty-eight SRs published in 59 journals were sampled. The median compliance with the PRISMA items was 17 (63%) out of 27 items (interquartile ratio=13-22 [48%-82%]). Two thirds of the SRs (n=66) focused on interventions for which efficacy is best addressed through a randomized controlled trial (RCT) design, and almost all of these SRs included RCTs (63/66 [95%]). More than two thirds of the SRs assessed the quality of primary studies (74/88 [84%]). Twenty-eight reviews (28/88 [32%]) meta-analyzed the results for at least one outcome. One half of the SRs reported positive statistically significant findings (46%), whereas a detrimental result was present only in one review. CONCLUSIONS: This sample of SRs in the rehabilitation field showed heterogeneous characteristics and a moderate quality of reporting. Poor control of potential source of bias might be improved if more widely agreed-upon evidence-based reporting guidelines will be actively endorsed and adhered to by authors and journals.

Patient empowerment as a component of health system reforms: rights, benefits and vested interests.

Different strategies have been developed across countries to foster citizens' and patients' involvement, from health policies to patients' active participation in decisions regarding their health. The spectrum varies from systems where patients lead the reform of health care services, to others where a paternalistic approach still limits patients' autonomy in decision-making. This paper describes: (1) different interventions for involving patients; (2) experiences to promote consumer evidence-based advocacy; and (3) barriers to consumer involvement in health system reforms, including vested interests in patients' associations. Citizens' involvement in health systems can vary substantially, but is gaining increasing weight.

Assessment of methodological quality of primary studies by systematic reviews: results of the metaquality cross sectional study.

OBJECTIVES: To describe how the methodological quality of primary studies is assessed in systematic reviews and whether the quality assessment is taken into account in the interpretation of results. DATA SOURCES: Cochrane systematic reviews and systematic reviews in paper based journals. STUDY SELECTION: 965 systematic reviews (809 Cochrane reviews and 156 paper based reviews) published between 1995 and 2002. DATA SYNTHESIS: The methodological quality of primary studies was assessed in 854 of the 965 systematic reviews (88.5%). This occurred more often in Cochrane reviews than in paper based reviews (93.9% v 60.3%, P < 0.0001). Overall, only 496 (51.4%) used the quality assessment in the analysis and interpretation of the results or in their discussion, with no significant differences between Cochrane reviews and paper based reviews (52% v 49%, P = 0.58). The tools and methods used for quality assessment varied widely. CONCLUSIONS: Cochrane reviews fared better than systematic reviews published in paper based journals in terms of assessment of methodological quality of primary studies, although they both largely failed to take it into account in the interpretation of results. Methods for assessment of methodological quality by systematic reviews are still in their infancy and there is substantial room for improvement.