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Background Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterised by the symptoms of inattention, impulsivity and hyperactivity. ADHD was once perceived as a condition of childhood only; however increasing evidence has highlighted the existence of ADHD in older adolescents and adults. Estimates for the prevalence of ADHD in adults range from 2.5–4%. Few data exist on the prescribing trends of the stimulants methylphenidate and dexamfetamine, and the non-stimulant atomoxetine in the UK. The aim of this study was to investigate the annual prevalence and incidence of pharmacologically treated ADHD in children, adolescents and adults in UK primary care. Methods The Health Improvement Network (THIN) database was used to identify all patients aged over 6 years with a diagnosis of ADHD/hyperkinetic disorder and a prescription for methylphenidate, dexamfetamine or atomoxetine from 2003–2008. Annual prevalence and incidence of pharmacologically treated ADHD were calculated by age category and sex. Results The source population comprised 3,529,615 patients (48.9% male). A total of 118,929 prescriptions were recorded for the 4,530 patients in the pharmacologically treated ADHD cohort during the 6-year study. Prevalence (per 1000 persons in the mid-year THIN population) increased within each age category from 2003 to 2008 [6–12 years: from 4.8 (95% CI: 4.5–5.1) to 9.2 (95% CI: 8.8–9.6); 13–17 years: from 3.6 (95% CI: 3.3–3.9) to 7.4 (95% CI: 7.0–7.8); 18–24 years: from 0.3 (95% CI: 0.2–0.3) to 1.1 (95% CI: 1.0–1.3); 25–45 years: from 0.02 (95% CI: 0.01–0.03) to 0.08 (95% CI: 0.06–0.10); >45 years: from 0.01 (95% CI: 0.00–0.01) to 0.02 (95% CI: 0.01–0.03). Whilst male patients aged 6-12 years had the highest prevalence; the relative increase in prescribing was higher amongst female patients of the same age - the increase in prevalence in females aged 6–12 years was 2.1 fold compared to an increase of 1.9 fold for their male counterparts. Prevalence of treated ADHD decreased with increasing age. Incidence (per 1000 persons at risk in the mid-year THIN population) was highest for children aged 6–12 years. Conclusions A trend of increasing prescribing prevalence of ADHD drug treatment was observed over the period 2003–2008. Prevalence of prescribing to adult patients increased; however the numbers treated are much lower than published estimates of the prevalence of ADHD. This study has added to the limited knowledge on ADHD prescribing in primary care, particularly in the area of drug treatment in adulthood.

Background Data collected within clinical trials often overlaps with routinely collected Health Systems Data (HSD). There is potential for HSD to reduce burdens for trials and understanding HSD use can help triallists make decisions about using HSD in future trials. However, it is unknown to what extent HSD use has been reported in trial publications, despite the development of guidelines such as ESMO-GROW and CONSORT-ROUTINE extension for reporting HSD use in trials. This study expands on work previously conducted by Lensen and colleagues (Trials 21(1):398, 2020). It aims to provide insights into how HSD use is reported in main result publications that present main trial results, before and after the release of the CONSORT-ROUTINE extension. Methods This was a systematic review of the reporting of HSD use in primary results publications of trials that accessed HSD between 2017 and 2018. Of 90 trials identified by Lensen and colleagues, those that had published primary outcome results were included in the review. Trials were excluded if (1) primary results were not yet due to be reported; (2) not yet published; (3) they were published prior to June 2017; (4) they were published in 2017, but HSD was accessed in 2018 and (5) the primary publication only reported HSD use in secondary, interim or Study Within a Trial (SWAT) analysis. Eligible publications were identified using ISRCTN, ClinicalTrials.gov, EU Clinical Trials Registries, PubMed and Embase. The reporting of HSD use was compared against expectations for reporting outlined in the CONSORT-ROUTINE extension. Results Forty-nine primary publications from 46 trials were included in the review . Overall, none of the included publications reported all the information suggested in the CONSORT-ROUTINE. However, there has been an improvement in the reporting of HSD use, since the publication of the CONSORT-ROUTINE guidelines. Conclusions Reporting of HSD use has improved over time. However, it still does not meet the expectations set out in the CONSORT-ROUTINE extension. Triallists should be encouraged to provide further information in publications about the use of HSD as per the CONSORT-ROUTINE extension guidelines. This would allow greater transparency in reporting, facilitating effective HSD use in future trials.

Background Routinely collected electronic health records (EHRs) have the potential to enhance randomised controlled trials (RCTs) by facilitating recruitment and follow-up. Despite this, current EHR use is minimal in UK RCTs, in part due to ongoing concerns about the utility (reliability, completeness, accuracy) and accessibility of the data. The aim of this manuscript is to document the process, timelines and challenges of the application process to help improve the service both for the applicants and data holders. Methods This is a qualitative paper providing a descriptive narrative from one UK clinical trials unit (MRC CTU at UCL) on the experience of two trial teams’ application process to access data from three large English national datasets: National Cancer Registration and Analysis Service (NCRAS), National Institute for Cardiovascular Outcomes Research (NICOR) and NHS Digital to establish themes for discussion. The underpinning reason for applying for the data was to compare EHRs with data collected through case report forms in two RCTs, Add-Aspirin (ISRCTN 74358648) and PATCH (ISRCTN 70406718). Results The Add-Aspirin trial, which had a pre-planned embedded sub-study to assess EHR, received data from NCRAS 13 months after the first application. In the PATCH trial, the decision to request data was made whilst the trial was recruiting. The study received data after 8 months from NICOR and 15 months for NHS Digital following final application submission. This concluded in May 2020. Prior to application submission, significant time and effort was needed particularly in relation to the PATCH trial where negotiations over consent and data linkage took many years. Conclusions Our experience demonstrates that data access can be a prolonged and complex process. This is compounded if multiple data sources are required for the same project. This needs to be factored in when planning to use EHR within RCTs and is best considered prior to conception of the trial. Data holders and researchers are endeavouring to simplify and streamline the application process so that the potential of EHR can be realised for clinical trials.

Background Anogenital warts are the second most common sexually transmitted infection diagnosed in sexual health services in England. About 90% of genital warts are caused by human papillomavirus (HPV) types 6 or 11, and half of episodes diagnosed are recurrences. The best and most cost-effective treatment for patients with anogenital warts is unknown. The commonly used treatments are self-administered topical agents, podophyllotoxin (0.15% cream) or imiquimod (5% cream), or cryotherapy with liquid nitrogen. Quadrivalent HPV (qHPV) vaccination is effective in preventing infection, and disease, but whether it has any therapeutic effect is not known. Methods and design To investigate the efficacy of clearance and prevention of recurrence of external anogenital warts by topical treatments, podophyllotoxin 0.15% cream or imiquimod 5% cream, in combination with a three-dose regimen of qHPV or control vaccination. 500 adult patients presenting with external anogenital warts with either a first or subsequent episode of anogenital warts will be entered into this randomised, controlled partially blinded 2 × 2 factorial trial. Discussion The trial is expected to provide the first high-quality evidence of the comparative efficacy and cost-effectiveness of the two topical treatments in current use, as well as investigate the potential benefit of HPV vaccination, in the management of anogenital warts. Trial registration The trial was registered prior to starting recruitment under the following reference numbers: International Standard Randomized Controlled Trial Number (ISRCTN) Registry - ISRCTN32729817 (registered 25 July 2014); European Union Clinical Trials Register (EudraCT) - 2013-002951-14 (registered 26 June 2013).

Background ADHD guidelines in the UK suggest that children and adults who respond to pharmacological treatment should continue for as long as remains clinically effective, subject to regular review. To what extent patients persist with treatment from childhood and adolescence into adulthood is not clear. This study aims to describe, in UK primary care, the persistence of pharmacological treatment for patients with ADHD who started treatment aged 6–17 years and to estimate the percentage of patients who continued treatment from childhood and adolescence into adulthood. Methods The Health Improvement Network (THIN) database was used to identify patients with ADHD who received their first prescription for methylphenidate/ dexamfetamine/atomoxetine, aged 6–17 years. Patients were monitored until their ‘censored date’ (the earliest of the following dates: date the last prescription coded in the database ended, end of the study period (31st December 2008), date at which they transferred out of their practice, date of death, the last date the practice contributed data to the database). Persistence of treatment into adulthood was estimated using Kaplan Meier analysis. Results 610 patients had follow-up data into adulthood. 213 patients (93.4% male) started treatment between 6–12 years; median treatment duration 5.9 years. 131 (61.5%) stopped before 18 years, 82 (38.5%) were still on treatment age ≥18 years. 397 patients (86.4% male) started treatment between 13–17 years; median treatment duration was 1.6 years. 227 (57.2%) stopped before 18 years, 170 (42.8%) were still on treatment age ≥18 years. The number of females in both age categories was too small to formally test for differences between genders in persistence of treatment. Conclusion Persistence of treatment into adulthood is lower (~40%) compared with published rates of persistence of the condition (~65% when symptomatic definition of remission used). Due to the limited number of patients with data past 18 years, it is important that ongoing monitoring of prescribing into later adulthood is undertaken, particularly to observe the effects of recommendations in new guidelines.

Rationale Autism spectrum disorders (ASDs) affect 1 % of children, having significant impact on health and social outcomes. Psychotropic medication use by individuals with ASD in the USA increased over time, and polypharmacy occurred in >50 % of those prescribed. In the UK, no psychotropic drugs are approved in ASDs, and little is known about patterns of pharmacological treatment in the ASD population and associated co-morbidities. Methods We used The Health Improvement Network, a nationally representative primary care database, to assess the prevalence of ASD diagnoses, psychotropic drug prescribing and neuropsychiatric co-morbidities of 0–24 year olds between 1992 and 2008. Results ASD prevalence increased 65-fold from 0.01 % (1992) to 0.50 % (2008). Psychotropic drugs were prescribed to 29 % (1,619/5,651) of the ASD cohort; the most prescribed drugs were sleep medication (9.7 % of prescribed patients), psychostimulants (7.9 %) and antipsychotics (7.3 %). More patients were given psychostimulants and sleep medications over time from 1.5–6.3 % and 2.2–5.9 % respectively. Thirty-seven per cent of the cohort had ≥1 record of a neuropsychiatric co-morbidity, the most common being developmental difficulties and learning disabilities (12.6 %), behavioural, conduct and personality disorders (11.1 %) and attention deficit hyperactivity disorder (7.5 %). Conclusions British physicians are more conservative in prescribing practice than American colleagues. However, use of psychostimulants and antipsychotics is much higher in those with ASD than in the general population. Polypharmacy was seen in 34 % of prescribed patients in 2008. Additional studies examining use, efficacy, and long-term safety of antipsychotics and psychostimulants in autistic individuals are warranted.

Objective: To provide an overview of drug use in children in three European countries. Design: Retrospective cohort study, 2000-5. Setting: Primary care research databases in the Netherlands (IPCI), United Kingdom (IMS-DA), and Italy (Pedianet). Participants: 675 868 children aged up to 14 (Italy) or 18 (UK and Netherlands). Main outcome measure: Prevalence of use per year calculated by drug class (anatomical and therapeutic). Prevalence of \"recurrent/chronic\" use (three or more prescriptions a year) and \"non-recurrent\" or \"acute\" use (less than three prescriptions a year) within each therapeutic class. Descriptions of the top five most commonly used drugs evaluated for off label status within each anatomical class. Results: Three levels of drug use could be distinguished in the study population: high (>10/100 children per year, moderate (1-10/100 children per year), and low (<1/100 children per year). For all age categories, anti-infective, dermatological, and respiratory drugs were in the high use group, whereas cardiovascular and antineoplastic drugs were always in the low use group. Emollients, topical steroids, and asthma drugs had the highest prevalence of recurrent use, but relative use of low prevalence drugs was more often recurrent than acute. In the top five highest prevalence drugs topical inhaled and systemic steroids, oral contraceptives, and topical or systemic antifungal drugs were most commonly used off label. Conclusion: This overview of outpatient paediatric prescription patterns in a large European population could provide information to prioritise paediatric therapeutic research needs.

Objectives The aims of this study were to provide a systematic review and meta-analysis of the effects of atypical antipsychotics in children and adolescents on weight gain (primary objective) and other metabolic parameters (secondary objective). Methods A systematic literature review and meta-analysis of double-blind, randomized, controlled trials were conducted. The data sources used were as follows: EMBASE, PubMed, BIOSIS, International Pharmaceutical Abstracts, The Cochrane database (Clinical Trials), Clinical Trials Government Registry, The metaRegister of Controlled Trials, WHO (World Health Organization) Clinical Trials Registry Platform, and PsycINFO ® . Hand searching was also carried out by examining the reference lists of identified studies. Double-blind, randomized, controlled trials investigating the metabolic adverse effects (weight gain, lipid, glucose, and prolactin level abnormalities) associated with atypical antipsychotic use in children and adolescents aged ≤18 years were included, irrespective of whether the investigation of adverse effects was a primary or secondary endpoint. Results We identified 21 studies of drug versus placebo that met the inclusion criteria, with a total of 2,455 patients, 14 studies for risperidone (1,331 patients), three for olanzapine (276 patients), and four for aripiprazole (848 patients). Compared with placebo, the mean weight increases for each drug were olanzapine 3.45 kg (95 % CI 2.93–3.98), risperidone 1.77 kg (95 % CI 1.35–2.20), and aripiprazole 0.94 kg (95 % CI 0.65–1.24). Regarding other metabolic abnormalities, eight studies reported statistically significant increases in prolactin with risperidone; two reported a statistically significant increase in glucose, total cholesterol, and prolactin with olanzapine; and three studies reported a statistically significant decrease in prolactin with aripiprazole. Data on lipid, glucose, and prolactin level changes were too limited to allow us to perform a meta-analysis. Conclusions Olanzapine, risperidone, and aripiprazole were all associated with statistically significant weight gain. Olanzapine was associated with the most weight gain and aripiprazole the least. For the secondary outcome, although a number of active comparator trials were identified, data were not available for meta-analysis and were too limited to allow firm conclusions to be drawn.

Anogenital warts are the second most common sexually transmitted infection diagnosed in sexual health services in England. About 90% of genital warts are caused by human papillomavirus (HPV) types 6 or 11, and half of episodes diagnosed are recurrences. The best and most cost-effective treatment for patients with anogenital warts is unknown. The commonly used treatments are self-administered topical agents, podophyllotoxin (0.15% cream) or imiquimod (5% cream), or cryotherapy with liquid nitrogen. Quadrivalent HPV (qHPV) vaccination is effective in preventing infection, and disease, but whether it has any therapeutic effect is not known. To investigate the efficacy of clearance and prevention of recurrence of external anogenital warts by topical treatments, podophyllotoxin 0.15% cream or imiquimod 5% cream, in combination with a three-dose regimen of qHPV or control vaccination. 500 adult patients presenting with external anogenital warts with either a first or subsequent episode of anogenital warts will be entered into this randomised, controlled partially blinded 2 x 2 factorial trial. The trial is expected to provide the first high-quality evidence of the comparative efficacy and cost-effectiveness of the two topical treatments in current use, as well as investigate the potential benefit of HPV vaccination, in the management of anogenital warts.

Background: Feasibility trials are often undertaken to determine whether a larger randomised controlled trial (RCT) is achievable. In a recent review, 15 feasibility trials accessed routinely collected health data (RCHD) from UK national databases and registries. This paper looks at attributes of these trials and the reasons why they accessed RCHD.  Methods: We extracted data from all publicly available sources for the 15 feasibility studies found in a previous review of trials successfully accessing RCHD in the UK between 2013-2018 for the purpose of informing or supplementing participant data. We extracted trial characteristics, the registry accessed, and the way the RCHD was used.  Results: The 15 feasibility RCTs were conducted in a variety of disease areas, and were generally small (median sample size 100, range 41-4061) and individually randomised (60%, 9/15). The primary trial outcome was predominantly administrative (non-clinical) (80%, 12/15) such as feasibility of patient recruitment. They were more likely to recruit from secondary care (67%, 10/15) settings than primary (33%, 5/15).  NHS Digital was the most commonly accessed registry (33% (5/15)) with SAIL databank (20% (3/15)), electronic Data Research and Innovation Service (eDRIS) and Paediatric Intensive Care Audit Network (PICANET) (each 13% 2/15) also being accessed. Where the information was clear, the trials used RCHD for data collection during the trial (47%, 7/15), follow-up after the trial (27%, 4/15) and recruitment (13%, 2/15).  Conclusions: Between 2013 and 2018, 15 feasibility trials successfully accessed UK RCHD. Feasibility trials would benefit, as with other trials, from guidance on reporting the use of RCHD in protocols and publications.