Target Product Profiles for medical tests: a systematic review of current methods.

BACKGROUND: A Target Product Profile (TPP) outlines the necessary characteristics of an innovative product to address an unmet clinical need. TPPs could be used to better guide manufacturers in the development of 'fit for purpose' tests, thus increasing the likelihood that novel tests will progress from bench to bedside. However, there is currently no guidance on how to produce a TPP specifically for medical tests. METHODS: A systematic review was conducted to summarise the methods currently used to develop TPPs for medical tests, the sources used to inform these recommendations and the test characteristics for which targets are made. Database and website searches were conducted in November 2018. TPPs written in English for any medical test were included. Based on an existing framework, test characteristics were clustered into commonly recognised themes. RESULTS: Forty-four TPPs were identified, all of which focused on diagnostic tests for infectious diseases. Three core decision-making phases for developing TPPs were identified: scoping, drafting and consensus-building. Consultations with experts and the literature mostly informed the scoping and drafting of TPPs. All TPPs provided information on unmet clinical need and desirable analytical performance, and the majority specified clinical validity characteristics. Few TPPs described specifications for clinical utility, and none included cost-effectiveness. CONCLUSIONS: We have identified a commonly used framework that could be beneficial for anyone interested in drafting a TPP for a medical test. Currently, key outcomes such as utility and cost-effectiveness are largely overlooked within TPPs though and we foresee this as an area for further improvement.

Critical Appraisal of International Clinical Practice Guidelines in Kidney Transplantation Using the Appraisal of Guidelines for Research and Education II Tool: A Systematic Review.

BACKGROUND: Although clinical practice guidelines (CPGs) are used for the development of local protocols in kidney transplantation (Ktx), the quality of their methodology is variable. This systematic review aimed to critically appraise international CPGs in all aspects of Ktx using the Appraisal of Guidelines for Research and Evaluation II tool. METHODS: Clinical Practice Guidelines in Ktx and donation published between 2010 and 2017 were identified from MEDLINE, Embase, National Guideline Clearinghouse, National Health Service and National Institute for Health and Care Excellence Evidence Searches, and the websites of transplant societies. Using Appraisal of Guidelines for Research and Evaluation II, 3 appraisers assessed the quality of CPGs. Interrater reliability was measured using the intraclass correlation coefficient (ICC). RESULTS: Searches identified 3168 records, and 115 CPGs were included. The highest scoring Appraisal of Guidelines for Research and Evaluation II domain was "scope and purpose" (80%; range, 30%-100%), followed by "clarity of presentation" (77%; range, 43%-98%), "editorial independence" (52%; range, 0%-94%), "rigor of development" (47%; range 6%-97%) and "stakeholder involvement" (41%; range, 11%-85%). The poorest scoring domain was "applicability" (31%; range, 3%-74%). Most CPGs were recommended for future use either with (63%) or without (18%) modifications. A small number (14%) were not recommended for future use or reviewers (5%) did not agree on recommending the CPG. The overall mean CPG quality score was 4 of 7 (range, 2-7). The mean ICC of 0.74 indicated substantial agreement between reviewers. CONCLUSIONS: The quality of international CPGs in Ktx was variable, and most CPGs lacked key aspects of methodological robustness and transparency. Improvements in methodology, patient involvement, and strategies for implementation are required.

Do clinical trials reflect reality? A systematic review of inclusion/exclusion criteria in trials of renal transplant immunosuppression.

Renal transplant recipients and donors are becoming increasingly more marginal, with more expanded criteria (ECD) and donation after circulatory death (DCD) donors and older recipients. Despite this, high-risk donors and recipients are often excluded from clinical trials, leading to uncertainty about the generalizability of findings. We extracted data regarding inclusion/exclusion criteria from 174 trials of immunosuppression in renal transplant recipients published over a 5-year period and compared criteria with those specified in published trial registries. Frequently reported donor exclusion criteria were age (16.1%), donor type and cold ischaemic time (22.4%). Common recipient exclusion criteria included upper age limit (38.5%), high panel reactive antibody (PRA) (42.5%) and previous transplantation (39.7%). Inclusion/exclusion criteria recorded in trial registries matched those reported in the manuscript in only 6 (7.8%) trials. Of registered trials, 51 (66.2%) trials included additional criteria in the manuscript, 51 (66.2%) were missing criteria in the manuscript specified in the protocol, and in 19 (24.7%) key criteria changed from the protocol to the manuscript. Our findings suggest many recent immunosuppression trials have restrictive inclusion criteria which may not be reflective of current renal transplant populations. Discrepancies between trial protocols and published reports raise the possibility of selection bias.