Original Title: Efectividad clínica del cribado neonatal de la hiperplasia suprarrenal congénita clásica por déficit de 21-OH. Actualización y análisis de los programas autonómicos

Authors' objectives: To update the evidence on the clinical effectiveness of neonatal screening for CAH due to 21-hydroxylase deficiency; to reassess the degree of compliance with national requirements for implementing screening programmes agreed in the “Framework Document on Population Screening” to serve as a basis for decision making on their inclusion in the neonatal screening programme in the common basic service portfolio of the Spanish National Health System.

Authors' results and conclusions: The systematic search retrieved 426 references, of which 29 were included because they met the previously defined selection criteria: 13 referring to screening programmes and 16 referring to disease characteristics. Through the manual review of the literature, the general internet search and regular updates up to April 2020, two additional studies, two economic evaluation reports and a screening programme were found, making a total of 32 studies included. Through the manual search on official government websites, the results of 11 screening programmes were located, of which 5 were included, making a total of 18 studies and screening programmes included. All selected studies and screening programmes were population-based cohort studies with prospective data collection, six of which were carried out in Europe. The quality of the studies was evaluated according to the QUADAS-2 tool for diagnostic validity studies, generally obtaining a low risk of bias and a high applicability. For the section on epidemiology and disease characteristics, 2 clinical practice guidelines and 6 systematic reviews were included, 4 with meta-analysis, all of high quality, evaluated with the AGREE II and AMSTAR-2 instruments, respectively. To assess efficiency, an economic evaluation report by the Evaluation Service of the Canary Islands Health System (SESCS) and a Canadian costeffectiveness study were included, and to assess social aspects, quality of life and the experiences and perceptions of patients, families and caregivers, two systematic reviews, an integrative review and a descriptive study were included. By disseminating the survey to patient associations and scientific societies, the direct participation of one patient representative and 4 family members/caregivers was achieved.

Authors' recommendations: – The evidence for the effectiveness of neonatal screening programmes of classic CAH assessed in this review is of moderate quality, and is based on population-based cohort studies with prospective data collection, systematic reviews with meta-analyses and clinical practice guidelines. – In classic CAH screening there is considerable heterogeneity in the screening algorithms in terms of cut-off stratification, recall criteria, reanalysis and/or referral to diagnostic confirmation, as well as in the protocols used (one or two-stage). – The test performance of single-stage screening programmes is limited, but is improved by adjusting positivity thresholds according to gestational age and/or birth weight and using the LC-MS/MS as a second-tier. The two-stage protocol reduces the false positive results and improves the positive predictive value. – It is estimated that in the absence of screening, about half of the cases may go undiagnosed or experience a diagnostic delay, especially in male newborns. – The updating of the evidence solves the existing doubts on 6 of the 9 essential requirements of implementation with uncertainty in the previous evaluation. Among these, the effectiveness of early treatment in improving the prognosis of the disease and the benefit in reducing morbidity stand out. However, the new evidence does not clarify the previous uncertainties about the benefit in terms of mortality, the validity of the test or the achievement of the expected benefit of the programme due to the short latency period requiring a rapid response time (especially in salt-wasting forms). – It is necessary to agree on an appropriate and specific screening algorithm and protocol that maximises the test performance and improves the comparability of the results, as well as to have a multidisciplinary clinical follow-up unit specialised in this illness. – It is recommended to establish specific indicators on health outcomes, and to define optimal and acceptable levels of some process indicators, such as the percentage of false positives. All this information will help to measure the achievement of the established quality objectives and the decision-making process.

Authors' methods: a systematic review of the scientific literature. A previous HTA report carried out in 2013 by Avalia-t was used as a starting point and the different search strategies were updated, taking into account the time limit used (2014 - present). The searches were carried out in the main biomedical databases: MedLine, Embase, Cochrane Library, HTA, DARE, INAHTA, CADTH, GIN, and Tripdatabse, among others, and the searches were regularly updated. The process was completed with a manual review of the bibliography of the articles included, and with a general internet search on the official websites of screening programmes, organisations and/or scientific societies. The titles and abstracts of the articles resulting from the search were reviewed by two researchers independently and blindly according to previously established selection criteria and resolving any discrepancies by consensus. The analysis also included data from the Spanish autonomous regions that include classic CAH screening in their additional screening programmes. This information was provided by the Screening Programmes Unit of the Spanish Ministry of Health. In order to incorporate the patients’ perspective and to determine the degree of acceptability, a data survey was designed that included specific aspects aimed at understanding the impact of the disease on the patient, family members and caregivers, and the experiences and expectations related to the screening process.

Project Status: Completed

Year Published: 2021

URL for published report: https://acis.sergas.es/cartafol/avalia-t201902-Cribado-HSC

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Spain

Organisation Name: Scientific Advice Unit, avalia-t; The Galician Health Knowledge Agency (ACIS)

Contact Address: Conselleria de Sanidade, Xunta de Galicia, San Lazaro s/n 15781 Santiago de Compostela, Spain. Tel: 34 981 541831; Fax: 34 981 542854;

Contact Name: avalia-t@sergas.es

Contact Email: avalia-t@sergas.es

Copyright: Galician Agency for Health Technology Assessment (AVALIA-T)