BackgroundIn cooperation with the Core Outcome Measures in Effectiveness Trials (COMET) initiative, the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) initiative aimed to develop a guideline on how to select outcome measurement instruments for outcomes (i.e., constructs or domains) included in a “Core Outcome Set” (COS). A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease or trial population.MethodsInformed by a literature review to identify potentially relevant tasks on outcome measurement instrument selection, a Delphi study was performed among a panel of international experts, representing diverse stakeholders. In three consecutive rounds, panelists were asked to rate the importance of different tasks in the selection of outcome measurement instruments, to justify their choices, and to add other relevant tasks. Consensus was defined as being achieved when 70 % or more of the panelists agreed and when fewer than 15 % of the panelists disagreed.ResultsOf the 481 invited experts, 120 agreed to participate of whom 95 (79 %) completed the first Delphi questionnaire. We reached consensus on four main steps in the selection of outcome measurement instruments for COS: Step 1, conceptual considerations; Step 2, finding existing outcome measurement instruments, by means of a systematic review and/or a literature search; Step 3, quality assessment of outcome measurement instruments, by means of the evaluation of the measurement properties and feasibility aspects of outcome measurement instruments; and Step 4, generic recommendations on the selection of outcome measurement instruments for outcomes included in a COS (consensus ranged from 70 to 99 %).ConclusionsThis study resulted in a consensus-based guideline on the methods for selecting outcome measurement instruments for outcomes included in a COS. This guideline can be used by COS developers in defining how to measure core outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1555-2) contains supplementary material, which is available to authorized users.

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BackgroundThe Core Outcome Measures in Effectiveness Trials (COMET) initiative aims to facilitate the development and application of ‘core outcome sets’ (COS). A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease or trial population. The overall aim of the Core Outcome Measurement Instrument Selection (COMIS) project is to develop a guideline on how to select outcome measurement instruments for outcomes included in a COS. As part of this project, we describe our current efforts to achieve a consensus on the methods for selecting outcome measurement instruments for outcomes to be included in a COS.Methods/DesignA Delphi study is being performed by a panel of international experts representing diverse stakeholders with the intention that this will result in a guideline for outcome measurement instrument selection. Informed by a literature review, a Delphi questionnaire was developed to identify potentially relevant tasks on instrument selection. The Delphi study takes place in a series of rounds. In the first round, panelists were asked to rate the importance of different tasks in the selection of outcome measurement instruments. They were encouraged to justify their choices and to add other relevant tasks. Consensus was reached if at least 70% of the panelists considered a task ‘highly recommended’ or ‘desirable’ and if no opposing arguments were provided. These tasks will be included in the guideline. Tasks that at least 50% of the panelists considered ‘not relevant’ will be excluded from the guideline. Tasks that were indeterminate will be taken to the second round. All responses of the first round are currently being aggregated and will be fed back to panelists in the second round. A third round will only be performed if the results of the second round require it.DiscussionSince the Delphi method allows a large group of international experts to participate, we consider it to be the preferred consensus-based method for our study. Based upon this consultation process, a guideline will be developed on instrument selection for outcomes to be included in a COS.

Dominant mutations in the skeletal muscle ryanodine receptor (RYR1) gene are well-recognized causes of both malignant hyperthermia susceptibility (MHS) and central core disease (CCD). More recently, recessive RYR1 mutations have been described in few congenital myopathy patients with variable pathology, including multi-minicores. Although a clinical overlap between patients with dominant and recessive RYR1 mutations exists, in most cases with recessive mutations the pattern of muscle weakness is remarkably different from that observed in dominant CCD. In order to characterize the spectrum of congenital myopathies associated with RYR1 mutations, we have investigated a cohort of 44 patients from 28 families with clinical and/or histopathological features suggestive of RYR1 involvement. We have identified 25 RYR1 mutations, 9 of them novel, including 12 dominant and 13 recessive mutations. With only one exception, dominant mutations were associated with a CCD phenotype, prominent cores and predominantly occurred in the RYR1 C-terminal exons 101 and 102. In contrast, the 13 recessive RYR1 mutations were distributed evenly along the entire RYR1 gene and were associated with a wide range of clinico-pathological phenotypes. Protein expression studies in nine cases suggested a correlation between specific mutations, RyR1 protein levels and resulting phenotype: in particular, whilst patients with dominant or recessive mutations associated with typical CCD phenotypes appeared to have normal RyR1 expression, individuals with more generalized weakness, multi-minicores and external ophthalmoplegia had a pronounced depletion of the RyR1 protein. The phenomenon of protein depletion was observed in some patients compound heterozygous for recessive mutations at the genomic level and silenced another allele in skeletal muscle, providing additional information on the mechanism of disease in these patients. Our data represent the most extensive study of RYR1-related myopathies and indicate complex genotype-phenotype correlations associated with mutations differentially affecting assembly and function of the RyR1 calcium release channel.