Introducing re-weighted range voting in clinical practice guideline prioritization: Development and testing of the re-weighted priority-setting (REPS) tool.

We aimed to develop and test a tool based on the re-weighted range voting mechanism to prioritize items (i.e. key questions) in a priority-setting assessment for clinical practice guidelines. The secondary aim was to provide methodological context of the tool. We iteratively developed the tool and used qualitative methods (i.e. think-aloud and semi-structured interviews) to test the tool's usability and make adjustments accordingly. An observational approach was used to test the tool's outcome satisfaction in a real-world priority-setting assessment within a rare-disease guideline of a European Reference Network and under four different conditions in the tool. Four guideline methodologists tested the usability of the tool. The real-world testing was performed with a guideline panel consisting of a core working group, five expertise working groups, and a working group with patient representatives. Thirty-one panel members assigned scores in the priority-setting assessment. Seventeen panel members rated the priority-setting outcome, and sixteen panel members rated the outputs generated under the four conditions. Upon initial use, guideline methodologists found the tool to be quite overwhelming. However, with some initial effort they were able to easily identify the tool's structure. Based on observations and feedback, the tool was further refined and user guidance was developed. Guideline panel members expressed (high) satisfaction with the priority-setting outcome. They particularly preferred the condition when using mean subgroup scores as input or employing aggressive penalties in the weighting method to determine the outputs. The tool generates a ranked list of items and offers flexibility for different choices in priority-setting assessments as long as its input format requirements are met. Although it is not a consensus method, the tool assists in narrowing down a set of priority items. Additional steps in the priority-setting assessment can lead to a consensus being reached regarding the final outcome.

Improving care for rare genetic neurodevelopmental disorders: A systematic review and critical appraisal of clinical practice guidelines using AGREE II.

PURPOSE: Rare genetic neurodevelopmental disorders associated with intellectual disability require lifelong multidisciplinary care. Clinical practice guidelines may support healthcare professionals in their daily practice, but guideline development for rare conditions can be challenging. In this systematic review, the characteristics and methodological quality of internationally published recommendations for this population are described to provide an overview of current guidelines and inform future efforts of European Reference Network ITHACA (Intellectual disability, TeleHealth, Autism, and Congenital Anomalies). METHODS: MEDLINE, Embase, and Orphanet were systematically searched to identify guidelines for conditions classified as "rare genetic intellectual disability" (ORPHA:183757). Methodological quality was assessed using the Appraisal of Guidelines, Research, and Evaluation II tool. RESULTS: Seventy internationally published guidelines, addressing the diagnosis and/or management of 28 conditions, were included. The methodological rigor of development was highly variable with limited reporting of literature searches and consensus methods. Stakeholder involvement and editorial independence varied as well. Implementation was rarely addressed. CONCLUSION: Comprehensive, high-quality guidelines are lacking for many rare genetic neurodevelopmental disorders. Use and transparent reporting of sound development methodologies, active involvement of affected individuals and families, robust conflict of interest procedures, and attention to implementation are vital for enhancing the impact of clinical practice recommendations.

[How often do medical guidelines refer to articles written in Dutch?] / Hoe vaak verwijzen richtlijnen naar artikelen in hetNTvG?

OBJECTIVE: For Dutch medical guidelines, Dutch research articles published in the NTvG (NederlandsTijdschriftvoorGeneeskunde) and other medical journals are not searched systematically and are only used sporadically. Using these publications in the process of guideline development can be useful for recommendations regarding the Dutch context of care. In this research, we have investigated how often and in which parts of Dutch guidelines articles published in NTvG are used. DESIGN: We specifically investigated how often articles published in NTvG are mentioned in Dutch medical guidelines published on www.richtlijnendatabase.nl, that were developed in 2019, 2020 and 2021. METHOD: In all parts of new or revised Dutch medical guidelines published in these years on www.richtlijnendatabase.nl, we searched for references of articles published in NTvG. RESULTS: The results show that in 3% of all Dutch medical guidelines a reference to an article published in NTvG is made. These references were made in the literature summaries (21% of the references), the reflections on the literature for the Dutch context of care (48% of the references), or in other areas such as the introduction (10% of the references) or appendices (21% of the references). CONCLUSION: Articles published in NTvG may be relevant for making recommendations in Dutch medical guidelines, as these publications usually reflect the Dutch care context, and may do more so than research published in international journals. The results of this research show that the number of Dutch guidelines where these articles are used is limited. Dutch research articles may be a source of information that is yet to be tapped into.

Rare disease registries: potential applications towards impact on development of new drug treatments.

BACKGROUND: Low prevalence, lack of knowledge about the disease course, and phenotype heterogeneity hamper the development of drugs for rare diseases. Rare disease registries (RDRs) can be helpful by playing a role in understanding the course of the disease, and providing information necessary for clinical trial design, if designed and maintained properly. We describe the potential applications of a RDR and what type of information should be incorporated to support the design of clinical trials in the process of drug development, based on a broad inventory of registry experience. We evaluated two existing RDRs in more detail to check the completeness of these RDRs for trial design. RESULTS: Before and during the application for regulatory approval a RDR can improve the efficiency and quality in clinical trial design by informing the sample size calculation and expected disease course. In exceptional circumstances information from RDRs has been used as historical controls for a one-armed clinical trial, and high quality RDRs may be used for registry-based randomized controlled trials. In the post marketing phase of (conditional) drug approval a disease-specific RDR is likely to provide more relevant information than a product-specific registry. CONCLUSIONS: A RDR can be very helpful to improve the efficiency and quality of clinical trial design in several ways. To enable the applicability and optimal use of a RDR longitudinal data collection is indispensable, and specific data collection, prepared for repeated measurement, is needed. The developed checklist can help to define the appropriate variables to include. Attention should be paid to the inclusion of patient-relevant outcome measures in the RDR from the start. More research and experience is needed on the possibilities and limitations of combining RDR information with clinical trial data to maximize the availability of relevant evidence for regulatory decisions in rare diseases.

A systematic review to investigate the measurement properties of goal attainment scaling, towards use in drug trials.

BACKGROUND: One of the main challenges for drug evaluation in rare diseases is the often heterogeneous course of these diseases. Traditional outcome measures may not be applicable for all patients, when they are in different stages of their disease. For instance, in Duchenne Muscular Dystrophy, the Six Minute Walk Test is often used to evaluate potential new treatments, whereas this outcome is irrelevant for patients who are already in a wheelchair. A measurement instrument such as Goal Attainment Scaling (GAS) can evaluate the effect of an intervention on an individual basis, and may be able to include patients even when they are in different stages of their disease. It allows patients to set individual goals, together with their treating professional. However, the validity of GAS as a measurement instrument in drug studies has never been systematically reviewed. Therefore, we have performed a systematic review to answer two questions: 1. Has GAS been used as a measurement instrument in drug studies? 2: What is known of the validity, responsiveness and inter- and intra-rater reliability of GAS, particularly in drug trials? METHODS: We set up a sensitive search that yielded 3818 abstracts. After careful screening, data-extraction was executed for 58 selected articles. RESULTS: Of the 58 selected articles, 38 articles described drug studies where GAS was used as an outcome measure, and 20 articles described measurement properties of GAS in other settings. The results show that validity, responsiveness and reliability of GAS in drug studies have hardly been investigated. The quality of the reporting of validity in studies in which GAS was used to evaluate a non-drug intervention also leaves much room for improvement. CONCLUSIONS: We conclude that there is insufficient information to assess the validity of GAS, due to the poor quality of the validity studies. Therefore, we think that GAS needs further validation in drug studies, especially since GAS can be a potential solution when a small heterogeneous patient group is all there is to test a promising new drug. TRIAL REGISTRATION: The protocol has been registered in the PROSPERO international prospective register for systematic reviews, with registration number CRD42014010619. http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014010619 .