OpenSAFELY: A platform for analysing electronic health records designed for reproducible research.

Electronic health records (EHRs) and other administrative health data are increasingly used in research to generate evidence on the effectiveness, safety, and utilisation of medical products and services, and to inform public health guidance and policy. Reproducibility is a fundamental step for research credibility and promotes trust in evidence generated from EHRs. At present, ensuring research using EHRs is reproducible can be challenging for researchers. Research software platforms can provide technical solutions to enhance the reproducibility of research conducted using EHRs. In response to the COVID-19 pandemic, we developed the secure, transparent, analytic open-source software platform OpenSAFELY designed with reproducible research in mind. OpenSAFELY mitigates common barriers to reproducible research by: standardising key workflows around data preparation; removing barriers to code-sharing in secure analysis environments; enforcing public sharing of programming code and codelists; ensuring the same computational environment is used everywhere; integrating new and existing tools that encourage and enable the use of reproducible working practices; and providing an audit trail for all code that is run against the real data to increase transparency. This paper describes OpenSAFELY's reproducibility-by-design approach in detail.

Dissemination of Registered COVID-19 Clinical Trials (DIRECCT): a cross-sectional study.

BACKGROUND: The results of clinical trials should be completely and rapidly reported during public health emergencies such as COVID-19. This study aimed to examine when, and where, the results of COVID-19 clinical trials were disseminated throughout the first 18 months of the pandemic. METHODS: Clinical trials for COVID-19 treatment or prevention were identified from the WHO ICTRP database. All interventional trials with a registered completion date ≤ 30 June 2021 were included. Trial results, published as preprints, journal articles, or registry results, were located using automated and manual techniques across PubMed, Google Scholar, Google, EuropePMC, CORD-19, the Cochrane COVID-19 Study Register, and clinical trial registries. Our main analysis reports the rate of dissemination overall and per route, and the time from registered completion to results using Kaplan-Meier methods, with additional subgroup and sensitivity analyses reported. RESULTS: Overall, 1643 trials with completion dates ranging from 46 to 561 days prior to the start of results searches were included. The cumulative probability of reporting was 12.5% at 3 months from completion, 21.6% at 6 months, and 32.8% at 12 months. Trial results were most commonly disseminated in journals (n = 278 trials, 69.2%); preprints were available for 194 trials (48.3%), 86 (44.3%) of which converted to a full journal article. Trials completed earlier in the pandemic were reported more rapidly than those later in the pandemic, and those involving ivermectin were more rapidly reported than other common interventions. Results were robust to various sensitivity analyses except when considering only trials in a "completed" status on the registry, which substantially increased reporting rates. Poor trial registry data on completion status and dates limits the precision of estimates. CONCLUSIONS: COVID-19 trials saw marginal increases in reporting rates compared to standard practice; most registered trials failed to meet even the 12-month non-pandemic standard. Preprints were common, complementing journal publication; however, registries were underutilized for rapid reporting. Maintaining registry data enables accurate representation of clinical research; failing to do so undermines these registries' use for public accountability and analysis. Addressing rapid reporting and registry data quality must be emphasized at global, national, and institutional levels.

Completeness and consistency of primary outcome reporting in COVID-19 publications in the early pandemic phase: a descriptive study.

BACKGROUND: The COVID-19 pandemic saw a steep increase in the number of rapidly published scientific studies, especially early in the pandemic. Some have suggested COVID-19 trial reporting is of lower quality than typical reports, but there is limited evidence for this in terms of primary outcome reporting. The objective of this study was to assess the prevalence of completely defined primary outcomes reported in registry entries, preprints, and journal articles, and to assess consistent primary outcome reporting between these sources. METHODS: This is a descriptive study of a cohort of registered interventional clinical trials for the treatment and prevention of COVID-19, drawn from the DIssemination of REgistered COVID-19 Clinical Trials (DIRECCT) study dataset. The main outcomes are: 1) Prevalence of complete primary outcome reporting; 2) Prevalence of consistent primary outcome reporting between registry entry and preprint as well as registry entry and journal article pairs. RESULTS: We analyzed 87 trials with 116 corresponding publications (87 registry entries, 53 preprints and 63 journal articles). All primary outcomes were completely defined in 47/87 (54%) registry entries, 31/53 (58%) preprints and 44/63 (70%) journal articles. All primary outcomes were consistently reported in 13/53 (25%) registry-preprint pairs and 27/63 (43%) registry-journal article pairs. No primary outcome was specified in 13/53 (25%) preprints and 8/63 (13%) journal articles. In this sample, complete primary outcome reporting occurred more frequently in trials with vs. without involvement of pharmaceutical companies (76% vs. 45%), and in RCTs vs. other study designs (68% vs. 49%). The same pattern was observed for consistent primary outcome reporting (with vs. without pharma: 56% vs. 12%, RCT vs. other: 43% vs. 22%). CONCLUSIONS: In COVID-19 trials in the early phase of the pandemic, all primary outcomes were completely defined in 54%, 58%, and 70% of registry entries, preprints and journal articles, respectively. Only 25% of preprints and 43% of journal articles reported primary outcomes consistent with registry entries.

E-cigarette manufacturers' compliance with clinical trial reporting expectations: a case series of registered trials by Juul Labs.

BACKGROUND: Electronic cigarettes (e-cigarettes) are a frequently debated topic in public health. It is essential that clinical trials examining e-cigarettes are fully and accurately reported, especially given long-standing concerns about tobacco industry research. We assess the reporting of clinical trials sponsored by Juul Labs, the largest e-cigarette company in the USA, against accepted reporting standards. METHODS: We searched ClinicalTrials.gov for all trials sponsored by Juul Labs and determined those with registry data consistent with coverage by the Food and Drug Administration (FDA) Amendments Act 2007 (FDAAA). For trials with a primary completion date more than 1 year earlier, we searched ClinicalTrials.gov, the academic literature and a Juul-funded research database (JLI Science) for results. For located results, we compared reported outcomes with registered outcomes in line with Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines. RESULTS: We located five registered trials sponsored by Juul Labs that appeared covered by the FDAAA 2007 in the public data. All five trials did not have results available on ClinicalTrials.gov. We found one publication and four poster presentations reporting results for four of the five covered trials outside of ClinicalTrials.gov. Of 61 specified outcomes, 28 were CONSORT compliant. Specific outcome reporting issues are detailed. DISCUSSION: Our findings raise substantial concerns regarding these trials. Clinicians, public health professionals, and the public cannot make informed choices about the benefits or hazards of e-cigarettes if the results of clinical trials are not completely and transparently reported. Clarification and potential enforcement of reporting laws may be required.

Preventable deaths involving opioids in England and Wales, 2013-2022: a systematic case series of coroners' reports.

BACKGROUND: Opioid deaths have increased in England and Wales. Coroners' Prevention of Future Deaths reports (PFDs) provide important insights that may enable safer use and avert harms, yet reports implicating opioids have not been synthesized. We aimed to identify opioid-related PFDs and explore coroners' concerns to prevent future deaths. METHODS: In this systematic case series, we screened 3897 coronial PFDs dated between 01 July 2013 and 23 February 2022, obtained by web scraping the UK's Courts and Tribunals Judiciary website. PFDs were included when an opioid was implicated in the death. Included PFDs were descriptively analysed, and content analysis was used to assess concerns reported by coroners. RESULTS: Opioids were involved in 219 deaths reported in PFDs (5·6% of PFDs), equating to 4418 years of life lost (median 33 years/person). Morphine (29%), methadone (23%) and diamorphine (16%) were the most common implicated opioids. Coroners most frequently raised concerns regarding systems and protocols (52%) or safety issues (15%). These concerns were most often addressed to National Health Service (NHS) organizations (51%), but response rates were low overall (47%). CONCLUSIONS: Opioids could be used more safely if coroners' concerns in PFDs were addressed by national organizations such as NHS bodies, government agencies and policymakers, as well as individual prescribing clinicians.

Severity of Severe Acute Respiratory System Coronavirus 2 (SARS-CoV-2) Alpha Variant (B.1.1.7) in England.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (B.1.1.7) is associated with higher transmissibility than wild-type virus, becoming the dominant variant in England by January 2021. We aimed to describe the severity of the alpha variant in terms of the pathway of disease from testing positive to hospital admission and death. METHODS: With the approval of NHS England, we linked individual-level data from primary care with SARS-CoV-2 community testing, hospital admission, and Office for National Statistics all-cause death data. We used testing data with S-gene target failure as a proxy for distinguishing alpha and wild-type cases, and stratified Cox proportional hazards regression to compare the relative severity of alpha cases with wild-type diagnosed from 16 November 2020 to 11 January 2021. RESULTS: Using data from 185 234 people who tested positive for SARS-CoV-2 in the community (alpha = 93 153; wild-type = 92 081), in fully adjusted analysis accounting for individual-level demographics and comorbidities as well as regional variation in infection incidence, we found alpha associated with 73% higher hazards of all-cause death (adjusted hazard ratio [aHR]: 1.73; 95% confidence interval [CI]: 1.41-2.13; P < .0001) and 62% higher hazards of hospital admission (1.62; 1.48-1.78; P < .0001) compared with wild-type virus. Among patients already admitted to the intensive care unit, the association between alpha and increased all-cause mortality was smaller and the CI included the null (aHR: 1.20; 95% CI: .74-1.95; P = .45). CONCLUSIONS: The SARS-CoV-2 alpha variant is associated with an increased risk of both hospitalization and mortality than wild-type virus.

Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform.

BACKGROUND: COVID-19 has disproportionately affected minority ethnic populations in the UK. Our aim was to quantify ethnic differences in SARS-CoV-2 infection and COVID-19 outcomes during the first and second waves of the COVID-19 pandemic in England. METHODS: We conducted an observational cohort study of adults (aged ≥18 years) registered with primary care practices in England for whom electronic health records were available through the OpenSAFELY platform, and who had at least 1 year of continuous registration at the start of each study period (Feb 1 to Aug 3, 2020 [wave 1], and Sept 1 to Dec 31, 2020 [wave 2]). Individual-level primary care data were linked to data from other sources on the outcomes of interest: SARS-CoV-2 testing and positive test results and COVID-19-related hospital admissions, intensive care unit (ICU) admissions, and death. The exposure was self-reported ethnicity as captured on the primary care record, grouped into five high-level census categories (White, South Asian, Black, other, and mixed) and 16 subcategories across these five categories, as well as an unknown ethnicity category. We used multivariable Cox regression to examine ethnic differences in the outcomes of interest. Models were adjusted for age, sex, deprivation, clinical factors and comorbidities, and household size, with stratification by geographical region. FINDINGS: Of 17 288 532 adults included in the study (excluding care home residents), 10 877 978 (62·9%) were White, 1 025 319 (5·9%) were South Asian, 340 912 (2·0%) were Black, 170 484 (1·0%) were of mixed ethnicity, 320 788 (1·9%) were of other ethnicity, and 4 553 051 (26·3%) were of unknown ethnicity. In wave 1, the likelihood of being tested for SARS-CoV-2 infection was slightly higher in the South Asian group (adjusted hazard ratio 1·08 [95% CI 1·07-1·09]), Black group (1·08 [1·06-1·09]), and mixed ethnicity group (1·04 [1·02-1·05]) and was decreased in the other ethnicity group (0·77 [0·76-0·78]) relative to the White group. The risk of testing positive for SARS-CoV-2 infection was higher in the South Asian group (1·99 [1·94-2·04]), Black group (1·69 [1·62-1·77]), mixed ethnicity group (1·49 [1·39-1·59]), and other ethnicity group (1·20 [1·14-1·28]). Compared with the White group, the four remaining high-level ethnic groups had an increased risk of COVID-19-related hospitalisation (South Asian group 1·48 [1·41-1·55], Black group 1·78 [1·67-1·90], mixed ethnicity group 1·63 [1·45-1·83], other ethnicity group 1·54 [1·41-1·69]), COVID-19-related ICU admission (2·18 [1·92-2·48], 3·12 [2·65-3·67], 2·96 [2·26-3·87], 3·18 [2·58-3·93]), and death (1·26 [1·15-1·37], 1·51 [1·31-1·71], 1·41 [1·11-1·81], 1·22 [1·00-1·48]). In wave 2, the risks of hospitalisation, ICU admission, and death relative to the White group were increased in the South Asian group but attenuated for the Black group compared with these risks in wave 1. Disaggregation into 16 ethnicity groups showed important heterogeneity within the five broader categories. INTERPRETATION: Some minority ethnic populations in England have excess risks of testing positive for SARS-CoV-2 and of adverse COVID-19 outcomes compared with the White population, even after accounting for differences in sociodemographic, clinical, and household characteristics. Causes are likely to be multifactorial, and delineating the exact mechanisms is crucial. Tackling ethnic inequalities will require action across many fronts, including reducing structural inequalities, addressing barriers to equitable care, and improving uptake of testing and vaccination. FUNDING: Medical Research Council.

Issues with reporting and interpretation of Khan et al. 2021.

A recent publication in BMC Infectious Diseases concerning the use of convalescent plasma for the treatment of COVID-19 had a number of major issues. This correspondence details specific instances of unclear reporting as well as major omissions when discussing the context of the trial. These render the study's findings and conclusions misleading.

Trends and variation in data quality and availability on the European Union Clinical Trials Register: A cross-sectional study.

BACKGROUND/AIMS: The European Union Clinical Trials Register is a public facing portal containing information on trials of medicinal products conducted under the purview of the European Union regulatory system. As of September 2021, the registry holds information on over 40,000 trials. Given its distinct regulatory purpose, and results reporting requirements, the European Union Clinical Trials Register should be a valuable open-source hub for trial information. Past work examining the European Union Clinical Trials Register has suggested that data quality on the registry may be lacking. We therefore set out to examine the quality and availability of trial data on the registry with a focus on areas that fall under the authority of regulators in each European Union/European Economic Area country. METHODS: Using data scraped from the full European Union Clinical Trials Register public dataset, we examined the extent of issues with three areas of trial data availability linked to European Union regulations. We examined whether there is evidence for missing registration of protocols in the public database, whether information on the completion of clinical trials is being made available and how often the results of trials are posted to the registry. We assessed each area overall, and examined variation between national regulators and over time. RESULTS: Major issues with the availability of expected protocols and information on trial completion were focused in a few countries. Overall, when comparing enrolment countries from tabular results to available registrations, 26,932 of 31,118 (86.5%) expected protocols were available and 22 of 30 (73%) countries had over 90% of expected protocols available. The majority of missing protocols, totalling 2764 (66%), were from just three countries: France, Norway and Poland. Evidence for this issue is further supported by data on trends in new registrations by country over time. Low availability of data on trial completion is also most pronounced in a minority of countries, like Spain and the Netherlands, with consistent trends for missingness over time. Finally, overall results availability is substantially worse among the 23,623 trials with a single registered European Union protocol (n = 6259, 26.5%) compared to 13,897 of those taking place in multiple countries (n = 8423, 60.6%). Reporting for single-protocol trials was consistently low across both time and location. CONCLUSION: Deficiencies in the public availability of trial protocols, trial completion information and summary results complicate the utility of the European Union Clinical Trials Register for research, transparency and accountability efforts. Users of the registry would benefit from a more complete and accurate accounting of the European research environment via the official European Union registry. We recommend regulators at the national and pan-national level undertake routine audits of approved trials to ensure national-level issues are proactively and transparently identified, documented and addressed.

Compliance with legal requirement to report clinical trial results on ClinicalTrials.gov: a cohort study.

BACKGROUND: Failure to report the results of a clinical trial can distort the evidence base for clinical practice, breaches researchers' ethical obligations to participants, and represents an important source of research waste. The Food and Drug Administration Amendments Act (FDAAA) of 2007 now requires sponsors of applicable trials to report their results directly onto ClinicalTrials.gov within 1 year of completion. The first trials covered by the Final Rule of this act became due to report results in January, 2018. In this cohort study, we set out to assess compliance. METHODS: We downloaded data for all registered trials on ClinicalTrials.gov each month from March, 2018, to September, 2019. All cross-sectional analyses in this manuscript were performed on data extracted from ClinicalTrials.gov on Sept 16, 2019; monthly trends analysis used archived data closest to the 15th day of each month from March, 2018, to September, 2019. Our study cohort included all applicable trials due to report results under FDAAA. We excluded all non-applicable trials, those not yet due to report, and those given a certificate allowing for delayed reporting. A trial was considered reported if results had been submitted and were either publicly available, or undergoing quality control review at ClinicalTrials.gov. A trial was considered compliant if these results were submitted within 1 year of the primary completion date, as required by the legislation. We described compliance with the FDAAA 2007 Final Rule, assessed trial characteristics associated with results reporting using logistic regression models, described sponsor-level reporting, examined trends in reporting, and described time-to-report using the Kaplan-Meier method. FINDINGS: 4209 trials were due to report results; 1722 (40·9%; 95% CI 39·4-42·2) did so within the 1-year deadline. 2686 (63·8%; 62·4-65·3) trials had results submitted at any time. Compliance has not improved since July, 2018. Industry sponsors were significantly more likely to be compliant than non-industry, non-US Government sponsors (odds ratio [OR] 3·08 [95% CI 2·52-3·77]), and sponsors running large numbers of trials were significantly more likely to be compliant than smaller sponsors (OR 11·84 [9·36-14·99]). The median delay from primary completion date to submission date was 424 days (95% CI 412-435), 59 days higher than the legal reporting requirement of 1 year. INTERPRETATION: Compliance with the FDAAA 2007 is poor, and not improving. To our knowledge, this is the first study to fully assess compliance with the Final Rule of the FDAAA 2007. Poor compliance is likely to reflect lack of enforcement by regulators. Effective enforcement and action from sponsors is needed; until then, open public audit of compliance for each individual sponsor may help. We will maintain updated compliance data for each individual sponsor and trial at fdaaa.trialstracker.net. FUNDING: Laura and John Arnold Foundation.

Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England, 16 November to 5 February.

The SARS-CoV-2 B.1.1.7 variant of concern (VOC) is increasing in prevalence across Europe. Accurate estimation of disease severity associated with this VOC is critical for pandemic planning. We found increased risk of death for VOC compared with non-VOC cases in England (hazard ratio: 1.67; 95% confidence interval: 1.34-2.09; p < 0.0001). Absolute risk of death by 28 days increased with age and comorbidities. This VOC has potential to spread faster with higher mortality than the pandemic to date.

Factors associated with the prescribing of high-dose opioids in primary care: a systematic review and meta-analysis.

BACKGROUND: The risks of harms from opioids increase substantially at high doses, and high-dose prescribing has increased in primary care. However, little is known about what leads to high-dose prescribing, and studies exploring this have not been synthesized. We, therefore, systematically synthesized factors associated with the prescribing of high-dose opioids in primary care. METHODS: We conducted a systematic review of observational studies in high-income countries that used patient-level primary care data and explored any factor(s) in people for whom opioids were prescribed, stratified by oral morphine equivalents (OME). We defined high doses as ≥ 90 OME mg/day. We searched MEDLINE, Embase, Web of Science, reference lists, forward citations, and conference proceedings from database inception to 5 April 2019. Two investigators independently screened studies, extracted data, and appraised the quality of included studies using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. We pooled data on factors using random effects meta-analyses and reported relative risks (RR) or mean differences with 95% confidence intervals (CI) where appropriate. We also performed a number needed to harm (NNTH) calculation on factors when applicable. RESULTS: We included six studies with a total of 4,248,119 participants taking opioids, of whom 3.64% (n = 154,749) were taking high doses. The majority of included studies (n = 4) were conducted in the USA, one in Australia and one in the UK. The largest study (n = 4,046,275) was from the USA. Included studies were graded as having fair to good quality evidence. The co-prescription of benzodiazepines (RR 3.27, 95% CI 1.32 to 8.13, I2 = 99.9%), depression (RR 1.38, 95% CI 1.27 to 1.51, I2 = 0%), emergency department visits (RR 1.53, 95% CI 1.46 to 1.61, I2 = 0%, NNTH 15, 95% CI 12 to 20), unemployment (RR 1.44, 95% CI 1.27 to 1.63, I2 = 0%), and male gender (RR 1.21, 95% CI 1.14 to 1.28, I2 = 78.6%) were significantly associated with the prescribing of high-dose opioids in primary care. CONCLUSIONS: High doses of opioids are associated with greater risks of harms. Associated factors such as the co-prescription of benzodiazepines and depression identify priority areas that should be considered when selecting, identifying, and managing people taking high-dose opioids in primary care. Coordinated strategies and services that promote the safe prescribing of opioids are needed. STUDY REGISTRATION: PROSPERO, CRD42018088057.

Bringing Transparency to Medicine: Exploring Physicians' Views and Experiences of the Sunshine Act.

The Physician Payments Sunshine Act (PPSA) requires health care product manufacturers to report to the federal government payments more than $10 to physicians. Bringing unprecedented transparency to medicine, PPSA holds great potential for enabling medical stakeholders to manage conflicts of interest (COI) and build patient trust-crucial responsibilities of medical professionalism. The authors conducted six focus groups with 42 physicians in Chicago, IL, San Francisco, CA, and Washington, DC, to explore attitudes and experiences around PPSA. Participants valued the concept of transparency but were wary of the law's design and consequences. They downplayed PPSA's potential and felt it undermined public trust. Showing broad unawareness of COI, they dismissed the notion of industry influence and welcomed company "perks." Misapprehensions may leave physicians unprepared to advance the opportunities PPSA holds for professionalism. The authors offer recommendations for government and medicine to improve physicians' and other stakeholders' understandings and use of the data.

Barriers and best practices to improving clinical trials transparency at UK public research institutions: A qualitative interview study.

OBJECTIVES: Since 2017, the UK government has made concerted efforts to ensure the dissemination of clinical trials conducted at public research institutions. This study aims to understand how stakeholders within these institutions responded to these pressures and modified internal policies and processes while identifying best practices and barriers to improved transparency practice. METHODS: Research governance and trial management staff from UK public research institutions (i.e., Universities and NHS Trusts) in England, Scotland and Wales participated in semi-structured interviews. Interviews were analysed using thematic analysis, aided by the framework method. RESULTS: Between November 2020 and July 2021, 14 individual participants were recruited from 11 different institutions. They worked in research governance, administration, and management. Almost universally, new policies and procedures have been established to ensure investigators are aware of, and supported in, fulfilling their transparency commitments, however challenges remain. Trials of medicinal products, as the most closely regulated research, consequently received the most attention. National professional networks aid in sharing knowledge and best practice within this community. CONCLUSIONS: Investment in the institutional governance of transparency is essential to achieving optimal transparency practices. Universities and hospitals share responsibility for ensuring research is performed and reported to regulatory standards. Facing political pressure, public research institutions in the UK have made efforts to improve their transparency practice which can provide key insights for similar efforts elsewhere.

Availability of results of clinical trials registered on EU Clinical Trials Register: cross sectional audit study.

Objective: To identify the availability of results for trials registered on the European Union Clinical Trials Register (EUCTR) compared with other dissemination routes to understand its value as a results repository. Design: Cross sectional audit study. Setting: EUCTR protocols and results sections, data extracted 1-3 December 2020. Population: Random sample of 500 trials registered on EUCTR with a completion date of more than two years from the beginning of searches (ie, 1 December 2018). Main outcome measures: Proportion of trials with results across the examined dissemination routes (EUCTR, ClinicalTrials.gov, ISRCTN registry, and journal publications), and for each dissemination route individually. Prespecified secondary outcomes were number and proportion of unique results, and the timing of results, for each dissemination route. Results: In the sample of 500 trials, availability of results on EUCTR (53.2%, 95% confidence interval 48.8% to 57.6%) was similar to the peer reviewed literature (58.6%, 54.3% to 62.9%) and exceeded the proportion of results available on other registries with matched records. Among the 383 trials with any results, 55 (14.4%, 10.9% to 17.9%) were only available on EUCTR. Also, after the launch of the EUCTR results database, median time to results was fastest on EUCTR (1142 days, 95% confidence interval 812 to 1492), comparable with journal publications (1226 days, 1074 to 1551), and exceeding ClinicalTrials.gov (3321 days, 1653 to undefined). For 117 trials (23.4%, 19.7% to 27.1%), however, results were published elsewhere but not submitted to the EUCTR registry, and no results were located in any dissemination route for 117 trials (23.4%, 19.7% to 27.1). Conclusions: EUCTR should be considered in results searches for systematic reviews and can help researchers and the public to access the results of clinical trials, unavailable elsewhere, in a timely way. Reporting requirements, such as the EU's, can help in avoiding research waste by ensuring results are reported. The registry's true value, however, is unrealised because of inadequate compliance with EU guidelines, and problems with data quality that complicate the routine use of the registry. As the EU transitions to a new registry, continuing to emphasise the importance of EUCTR and the provision of timely and complete data is critical. For the future, EUCTR will still hold important information from the past two decades of clinical research in Europe. With increased efforts from sponsors and regulators, the registry can continue to grow as a source of results of clinical trials, many of which might be unavailable from other dissemination routes.