Real-world data and evidence in health technology assessment: When are they complementary, substitutes, or the only sources of data compared to clinical trials?

Within the life-cycle assessment of health technologies, real-world data (RWD) have until now been of secondary importance to clinical trial data. The availability of massive, better quality RWD, particularly with the emergence of connected devices, the improvement of methods for characterizing populations, make it possible to have a better insight into the effects of treatment, sometimes on a national scale the importance of RWD is likely to progress in the eyes of health technology assessors, going from being traditionally complementary to possibly replacing clinical trial data. This is the fundamental question that the round table, involving experts from the academic and/or hospital, institutional, and industrial worlds, set out to answer. This work served first to establish the current role of RWD in health technology assessment, by distinguishing the main purposes of RWD, the timing of the evaluation in relation to the life cycle of the technology, and then according to the party commissioning or receiving the outcomes of RWD-based studies. Secondly, the round table proposed six general recommendations for more intensive and decisive use of RWD in the assessment and decision-making process.

Requests for post-registration studies (PRS), patients follow-up in actual practice: Changes in the role of databases.

Early market access of health products is associated with a larger number of requests for information by the health authorities. Compared with these expectations, the growing expansion of health databases represents an opportunity for responding to questions raised by the authorities. The computerised nature of the health system provides numerous sources of data, and first and foremost medical/administrative databases such as the French National Inter-Scheme Health Insurance Information System (SNIIRAM) database. These databases, although developed for other purposes, have already been used for many years with regard to post-registration studies (PRS). The use thereof will continue to increase with the recent creation of the French National Health Data System (SNDS [2016 health system reform law]). At the same time, other databases are available in France, offering an illustration of "product use under actual practice conditions" by patients and health professionals (cohorts, specific registries, data warehouses, etc.). Based on a preliminary analysis of requests for PRS, approximately two-thirds appeared to have found at least a partial response in existing databases. Using these databases has a number of disadvantages, but also numerous advantages, which are listed. In order to facilitate access and optimise their use, it seemed important to draw up recommendations aiming to facilitate these developments and guarantee the conditions for their technical validity. The recommendations drawn up notably include the need for measures aiming to promote the visibility of research conducted on databases in the field of PRS. Moreover, it seemed worthwhile to promote the interoperability of health data warehouses, to make it possible to match information originating from field studies with information originating from databases, and to develop and share algorithms aiming to identify criteria of interest (proxies). Methodological documents, such as the French National Authority for Health (HAS) recommendations on "Les études post-inscription sur les technologies de santé (médicaments, dispositifs médicaux et actes). Principes et méthodes" [Post-registration studies on health technologies (medicinal products, medical devices and procedures). Principles and methods] should be updated to incorporate these developments.

Patients With Ischemic Stroke and Incident Atrial Fibrillation: A Nationwide Cohort Study.

BACKGROUND AND PURPOSE: A substantial part of ischemic strokes is attributed to atrial fibrillation (AF). We hypothesized that patients with ischemic stroke without prior diagnosed AF were at higher risk of having a subsequent diagnosis of AF, and this was associated with multiple risk factors. METHODS: This French longitudinal cohort study was based on the national database covering hospital care from 2008 to 2012 for the entire population. RESULTS: Of 65 807 patients with ischemic stroke in 2009, 48 992 did not have AF at baseline. A total of 4828 of these patients were diagnosed as having AF during a follow-up of 15±15 months (incidence rate 7.9 per 100 person-years). By comparison, the yearly rate of new-onset AF for the 826 416 patients with a cardiac hospitalization was 5.9%. CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack) and CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack [doubled], vascular disease, age 65-75 years, and sex category [female]) scores were both associated with the risk of new-onset AF during follow-up (CHADS2: hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.66-1.75; CHA2DS2-VASc: HR 1.45, 95% CI 1.42-1.48). The c statistics were 0.700 (95% CI 0.696-0.706) for CHADS2 and 0.706 (95% CI 0.702-0.710) with CHA2DS2-VASc (P=0.003 for comparison of the 2 scores). Independent predictors of subsequent diagnosis of AF were age 65 to 74 years (HR 2.29, 95% CI 2.06-2.54), age ≥75 years (HR 3.31, 95% CI 3.02-3.64), hypertension (HR 1.22, 95% CI 1.13-1.32), heart failure (HR 2.56, 95% CI 2.41-2.72), and vascular disease (HR 1.10, 95% CI 1.04-1.17). CONCLUSIONS: Ischemic stroke was associated with a substantially increased risk of incident AF, particularly among individuals with higher CHADS2 or CHA2DS2-VASc scores. These risk scores seem to be simple tools for identifying patients at higher risk of incident AF after ischemic stroke.

Comparison of pharmacokinetic variables for creatinine and iohexol in dogs with various degrees of renal function.

OBJECTIVE: To compare pharmacokinetics and clearances of creatinine and iohexol as estimates of glomerular filtration rate (GFR) in dogs with various degrees of renal function. ANIMALS: 50 Great Anglo-Francais Tricolor Hounds with various degrees of renal function. PROCEDURES: Boluses of iohexol (40 mg/kg) and creatinine (647 mg/kg) were injected IV. Blood samples were collected before administration and 5 and 10 minutes and 1, 2, 4, 6, and 8 hours after administration. Plasma creatinine and iohexol concentrations were assayed via an enzymatic method and high-performance liquid chromatography, respectively. A noncompartmental approach was used for pharmacokinetic analysis. Pharmacokinetic variables were compared via a Bland-Altman plot and an ANOVA. RESULTS: Compared with results for creatinine, iohexol had a significantly higher mean ± SD plasma clearance (3.4 ± 0.8 mL/min/kg vs 3.0 ± 0.7 mL/min/kg) and a significantly lower mean volume of distribution at steady state (250 ± 37 mL/kg vs 539 ± 73 mL/kg), mean residence time (80 ± 31 minutes vs 195 ± 73 minutes), and mean elimination half-life (74 ± 20 minutes vs 173 ± 53 minutes). Despite discrepancies between clearances, especially for high values, the difference was < 0.6 mL/min/kg for 34 (68%) dogs. Three dogs with a low GFR (< 2 mL/min/kg) were classified similarly by both methods. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma iohexol and creatinine clearances can be used interchangeably for screening patients suspected of having chronic kidney disease (ie, low GFR), but large differences may exist for dogs with a GFR within or above the reference range.