Les objectifs de cette thèse étaient de produire des connaissances nouvelles sur les méthodologies d’évaluation de l’optimalité des soins avec l’exemple des délais diagnostiques et des infections bactériennes sévères de l’enfant (IBS). Nous avons mis en évidence, dans deux revues systématiques de la littérature, que les points méthodologiques potentiellement associés à des risques de biais et d’obstacles à la transportabilité des résultats étaient rarement rapportés dans les études primaires sur les délais diagnostiques ou rarement évalués par les auteurs de méta-analyses. Nous avons donc construit et validé internationalement une reporting guideline pour aider les scientifiques à prendre en compte ces points méthodologiques critiques. Nous avons montré par une enquête confidentielle avec comité d’experts en population que : (i) les prises en charge étaient suboptimales pour 76% des enfants décédés d’IBS, (ii) un retard au recours médical, une sous-évaluation de la gravité ou un retard à l’antibiothérapie étaient retrouvés dans la prise en charge de respectivement 20%, 20% et 24% des enfants atteints d’IBS, (iii) les soins suboptimaux étaient indépendamment et fortement associés au risque de décès et (iv) les soins suboptimaux étaient plus fréquents chez les enfants de moins d’un an ou lorsque qu’ils n’étaient pas administrés par un médecin spécifiquement formé. La minimisation des biais dans la sélection des participants et la mesure de l’optimalité et la prise en compte de facteurs de confusion comme la sévérité intrinsèque de la maladie sont des éléments clefs de l’évaluation de l’optimalité des soins afin de produire des messages cliniques correctifs valides. / The aim of this thesis was to product new knowledge about the methodology on how to assess the optimality of care with the examples of time to diagnosis and serious bacterial infection (SBI). In two systematic reviews, we found that the key methodological points potentially related to risks of bias or threats to transportability were rarely reported in the primary studies and rarely evaluated by authors of systematic reviews. Then, we developed and internationally validated a reporting guideline to help scientists to better take into consideration these critical methodological points. In a population-based confidential inquiry, we found that: (i) care was suboptimal in 76% of the initial management of children who died from SBI, (ii) delayed first medical contact, undervaluation of severity or delayed antibiotic administration were detected in the management of 20%, 20% and 24% of children admitted to intensive care for a SBI, respectively, (iii) the total number of suboptimal cares delivered during the management was independently associated with death, and (iv) suboptimal cares were more frequent in children younger than one year old and if the care was delivered by a non specialist physician. Minimizing the risks of bias both in the selection process of the study population and in the assessment of the optimality of care, and taking into account confounding factors such as the intrinsic severity of the disease are keys elements to ensure a reliable evaluation of optimality of care in order to produce effective corrective clinical messages.

Increasing time trends in the recorded incidence of childhood cancer have been reported in many different settings. The extent to which these trends reflect real changes in incidence, rather than improvements in methods for diagnosis and registration, is controversial. Using data from the National Registry of Childhood Tumours (NRCT), this thesis investigates time trends in cancer diagnosed under age 15 in residents of Britain during 1966-2005 (54650 cases), and considers potential sources of artefact in detail. Several different methods are used to estimate completeness of NRCT registration. The history of methods for diagnosis and registration of childhood cancers in Britain is described, and predictions are made for effects on recorded incidence. For each of the 12 main diagnostic groups, Poisson regression is used to fit continuous time trends and ‘step’ models to the annual age-sex-standardised rates by year of birth and year of diagnosis. Age-specific rates by period, and quinquennial standardised rates for diagnostic subgroups, are shown graphically. For three broad groups (leukaemia, CNS tumours and other cancer), geographical variation is compared by period of diagnosis. The results of these analyses are discussed in relation to the predicted artefacts. The evidence for a positive association between affluence and recorded incidence of childhood leukaemia is briefly reviewed. A special form of diagnostic artefact, the ‘fatal infection’ hypothesis, is proposed as an explanation of both this association and the leukaemia time trend. This hypothesis is examined in a novel test based on clinical data. The recorded incidence of childhood cancer in Britain increased in each of 12 diagnostic groups during 1966-2005 (from 0.5% per year for bone cancer to 2.5% for hepatic cancer, with 0.7% for leukaemia). Evidence presented here suggests that these increases are probably artefacts of diagnosis and registration. The potential implications for epidemiological studies of childhood cancer should be considered.