Latest trends in ADHD drug prescribing patterns in children in the UK: prevalence, incidence and persistence.

OBJECTIVES: To investigate attention deficit and hyperactivity disorder (ADHD) drug prescribing in children under 16 years old in the UK between 1992 and 2013. METHODS: All patients under 16 registered in the Clinical Practice Research Datalink (CPRD) with a minimum of 1 year of observation time and who received at least one prescription of any ADHD drug between 1 January 1992 and 31 December 2013.Trends in prevalence and incidence of use of ADHD drugs in children were calculated between 1995 and 2013 and persistence in new users was estimated. RESULTS: The prevalence of ADHD drug use in children under 16 increased 34-fold overall, rising from 1.5 95% CI (1.1 to 2.0) per 10 000 children in 1995 to 50.7 95% CI (49.2 to 52.1) per 10 000 children in 2008 then stabilising to 51.1 95% CI (49.7 to 52.6) per 10 000 children in 2013. The rate of new users increased eightfold reaching 10.2 95% CI (9.5 to 10.9) per 10 000 children in 2007 then decreasing to 9.1 95% CI (8.5 to 9.7) per 10 000 children in 2013. Although prevalence and incidence increased rather steeply after 1995, this trend seems to halt from 2008 onwards. We identified that 77%, 95% CI (76% to 78%) of children were still under treatment after 1 year and 60% 95% CI (59% to 61%) after 2 years. CONCLUSIONS: There was a marked increase in ADHD drug use among children in the UK from 1992 until around 2008, with stable levels of use since then. UK children show relatively long persistence of treatment with ADHD medications compared to other countries

Implementing high-dimensional propensity score principles to improve confounder adjustment in UK electronic health records.

PURPOSE: Recent evidence from US claims data suggests use of high-dimensional propensity score (hd-PS) methods improve adjustment for confounding in non-randomised studies of interventions. However, it is unclear how best to apply hd-PS principles outside their original setting, given important differences between claims data and electronic health records (EHRs). We aimed to implement the hd-PS in the setting of United Kingdom (UK) EHRs. METHODS: We studied the interaction between clopidogrel and proton pump inhibitors (PPIs). Whilst previous observational studies suggested an interaction (with reduced effect of clopidogrel), case-only, genetic and randomised trial approaches showed no interaction, strongly suggesting the original observational findings were subject to confounding. We derived a cohort of clopidogrel users from the UK Clinical Practice Research Datalink linked with the Myocardial Ischaemia National Audit Project. Analyses estimated the hazard ratio (HR) for myocardial infarction (MI) comparing PPI users with non-users using a Cox model adjusting for confounders. To reflect unique characteristics of UK EHRs, we varied the application of hd-PS principles including the level of grouping within coding systems and adapting the assessment of code recurrence. Results were compared with traditional analyses. RESULTS: Twenty-four thousand four hundred and seventy-one patients took clopidogrel, of whom 9111 were prescribed a PPI. Traditional PS approaches obtained a HR for the association between PPI use and MI of 1.17 (95% CI: 1.00-1.35). Applying hd-PS modifications resulted in estimates closer to the expected null (HR 1.00; 95% CI: 0.78-1.28). CONCLUSIONS: hd-PS provided improved adjustment for confounding compared with other approaches, suggesting hd-PS can be usefully applied in UK EHRs

Angiotensin receptor blockers and risk of dementia: cohort study in UK Clinical Practice Research Datalink.

AIMS: This was a cohort study to evaluate whether individuals exposed to angiotensin receptor blockers have a reduced risk of dementia compared with those exposed to angiotensin-converting enzyme inhibitors. METHODS: The study included new users of angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (from 1995 to 2010) from UK primary care practices contributing to the Clinical Research Practice Datalink. The association between exposure to angiotensin receptor blockers and the risk of incident dementia was analysed using a Cox model, adjusting for age, sex, body mass index, diabetes, hypertension, heart failure, statin use, socioeconomic status, alcohol, smoking, number of consultations and calendar year. RESULTS: A total of 426 089 persons were included in the primary analysis, with 45 541 persons exposed to angiotensin receptor blockers and the remainder to angiotensin-converting enzyme inhibitors. The total number of new diagnoses of dementia was 6517. There was weak evidence of a decreased risk of dementia with exposure to angiotensin receptor blockers, with follow-up beginning at 1 year after the start of treatment (adjusted hazard ratio 0.92, 95% confidence interval 0.85-1.00). An analysis restricted to the first 12 months after the index date showed a larger effect on dementia risk (adjusted hazard ratio 0.60, 95% confidence interval 0.50-0.72). CONCLUSIONS: A small reduction in dementia risk was seen with angiotensin receptor blockers in comparison to angiotensin-converting enzyme inhibitors. However, the strongest association was seen in early follow-up, suggesting that the inverse association is unlikely to be causal, but instead reflects other important but unmeasured differences between angiotensin receptor blocker and angiotensin-converting enzyme inhibitor users

Lessons to be learned from test evaluations during the Covid-19 pandemic:RSS Working Group’s Report on Diagnostic Tests

The coronavirus disease (Covid-19) pandemic raised challenges for everyday life. Development of new diagnostic tests was necessary, but under such enormous pressure risking inadequate evaluation. Against a background of concern about standards applied to the evaluation of in vitro diagnostic tests (IVDs), clear statistical thinking was needed on the principles of diagnostic testing in general, and their application in a pandemic. Therefore, in July 2020, the Royal Statistical Society convened a Working Group of six biostatisticians to review the statistical evidence needed to ensure the performance of new tests, especially IVDs for infectious diseases—for regulators, decision-makers, and the public. The Working Group’s review was undertaken when the Covid-19 pandemic shone an unforgiving light on current processes for evaluating and regulating IVDs for infectious diseases. The report’s findings apply more broadly than to the pandemic and IVDs, to diagnostic test evaluations in general. A section of the report focussed on lessons learned during the pandemic and aimed to contribute to the UK Covid-19 Inquiry’s examination of the response to, and impact of, the Covid-19 pandemic to learn lessons for the future. The review made 22 recommendations on what matters for study design, transparency, and regulation

Approaches for combining primary care electronic health record data from multiple sources: a systematic review of observational studies.

OBJECTIVE: To identify observational studies which used data from more than one primary care electronic health record (EHR) database, and summarise key characteristics including: objective and rationale for using multiple data sources; methods used to manage, analyse and (where applicable) combine data; and approaches used to assess and report heterogeneity between data sources. DESIGN: A systematic review of published studies. DATA SOURCES: Pubmed and Embase databases were searched using list of named primary care EHR databases; supplementary hand searches of reference list of studies were retained after initial screening. STUDY SELECTION: Observational studies published between January 2000 and May 2018 were selected, which included at least two different primary care EHR databases. RESULTS: 6054 studies were identified from database and hand searches, and 109 were included in the final review, the majority published between 2014 and 2018. Included studies used 38 different primary care EHR data sources. Forty-seven studies (44%) were descriptive or methodological. Of 62 analytical studies, 22 (36%) presented separate results from each database, with no attempt to combine them; 29 (48%) combined individual patient data in a one-stage meta-analysis and 21 (34%) combined estimates from each database using two-stage meta-analysis. Discussion and exploration of heterogeneity was inconsistent across studies. CONCLUSIONS: Comparing patterns and trends in different populations, or in different primary care EHR databases from the same populations, is important and a common objective for multi-database studies. When combining results from several databases using meta-analysis, provision of separate results from each database is helpful for interpretation. We found that these were often missing, particularly for studies using one-stage approaches, which also often lacked details of any statistical adjustment for heterogeneity and/or clustering. For two-stage meta-analysis, a clear rationale should be provided for choice of fixed effect and/or random effects or other models

Detecting Signals of Disproportionate Reporting from Singapore's Spontaneous Adverse Event Reporting System: An Application of the Sequential Probability Ratio Test.

INTRODUCTION: The ability to detect safety concerns from spontaneous adverse drug reaction reports in a timely and efficient manner remains important in public health. OBJECTIVE: This paper explores the behaviour of the Sequential Probability Ratio Test (SPRT) and ability to detect signals of disproportionate reporting (SDRs) in the Singapore context. METHODS: We used SPRT with a combination of two hypothesised relative risks (hRRs) of 2 and 4.1 to detect signals of both common and rare adverse events in our small database. We compared SPRT with other methods in terms of number of signals detected and whether labelled adverse drug reactions were detected or the reaction terms were considered serious. The other methods used were reporting odds ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN) and Gamma Poisson Shrinker (GPS). RESULTS: The SPRT produced 2187 signals in common with all methods, 268 unique signals, and 70 signals in common with at least one other method, and did not produce signals in 178 cases where two other methods detected them, and there were 403 signals unique to one of the other methods. In terms of sensitivity, ROR performed better than other methods, but the SPRT method found more new signals. The performances of the methods were similar for negative predictive value and specificity. CONCLUSIONS: Using a combination of hRRs for SPRT could be a useful screening tool for regulatory agencies, and more detailed investigation of the medical utility of the system is merited