全球数据的协调：弥合地方登记处之间的差距

The clinical trial disclosure space has evolvedconsiderably over the more than two decadessince the US introduced ClinicalTrials.gov in2000. ClinicalTrials.gov, a system that startedwith a mere 1,255 registered trials within itsfirst year1, now has 473,067 registered trials.2International Committee of Medical JournalEditors (ICMJE) policy requires studies to beregistered to be considered for publication. Andclinical trial registries have been established incountries across the globe. There are currently at least 79 countries withclinical trial disclosure requirements, including31 countries that follow European Union(EU) requirements. And there are currently40 countries with at least one clinical trialregistry (see Table 1) as well as regionalregistries including CTIS (the EMA Clinical TrialInformation System), PACTR (the pan-AfricanClinical Trial Registry), and ISRCTN (a globalregistry based in the UK). In one systematic review of 197 randomizedclinical trials registered in more than one trialregistry, sponsor and funder had the highestlevel of agreement among registries. However,agreement level declined as the investigatorsworked their way down the list of data points(see Figure 1).3 With these growing registries comes thechallenge of submitting multinational clinicaltrial data. Each registry has its own datastandards and requirements, and there is oftena lack of overlap between the information eachregistry requires in their submissions. Thatcan lead to inconsistencies in the data amongregistries. Regulators zeroing in on disclosurecomplianceIn the past, there has been little enforcement of In Europe, enforcement of disclosure rules is leftup to the individual member states.6Fourteenout of the 30 European Economic Area (EEA)member states have stated they will imposefines ranging in the thousands of euros for thosewho do not comply with disclosure regulations.Belgium has one of the steepest penalties, withfines of up to €500,000 and up to three years inprison for noncompliance.7 disclosure rules. But in recent years, regulatorsin many regions have begun to enforce the rulesaround clinical trials disclosure — particularlydisclosure of results. Since 2021, the US Food and DrugAdministration (FDA) has issued several publicnotices of noncompliance to sponsors that havefailed to comply with certain requirements forregistering and submitting results information toClinicalTrials.gov.4The FDA’s maximum penaltiesfor these violations are $14,262 per violationthat isn’t corrected within 30 days of notice plus$14,262 per day of violation after that 30-dayperiod.5All sponsors receiving public noticesaddressed the issues raised, saving them fromthese penalties.4Still, this shows the FDA istaking a more active role in ensuring sponsorsare keeping up with disclosure rules. Though the EU and European Medicines Agency(EMA) haven’t published any lists of sponsorsin noncompliance with their rules, they haveindicated in the past that sponsors often don’tpost results to EudraCT. For example, theEMA noted that as of April 2019, the EudraCTdatabase included a total of 57,687 clinical trials,of which 47% were completed.8Out of thesecompleted trials, sponsors had complied withthe publication requirements for 68%, but resultswere still lacking for 32%.8 Currently, the EMA’s Clinical Trial InformationSystem (CTIS), which went fully live in January2022, has 2,395 registered trials2, with some ofthose trials being transitioned from EudraCTto CTIS. This total falls short of the estimated8,000 clinical trial applications9taking place inthe EU each year. exclusion criteria, while other registries mayhave drop-down menus or radio buttons withpreset text. These differences make alignmentdifficult, if not impossible. This also can present a challenge when handlingcomplex study designs. In some cases, it can bedifficult to accurately represent complex studydesigns and protocols in a way that aligns withregistry requirements. One registry may haveextensive and detailed data fields, while anothermay be more limited in scope. Depending onthe study, there is also the issue of ensuring allrequired information is provided in each registry. The bottom line: Some sponsors may be fallingbehind on disclosure in the EU, which couldhave them running afoul of EU member states’disclosure regulations and leave them open topenalties. Disclosure content challengesFor trials conducted in multiple countries, the There is often a need to frequently updateand amend trial data as the trial progresses,which can be cumbersome and time consumingwhen multiple registries are involved. It canbe challenging to ensure that the relevant trialregistries are updated with consistent data toreflect the updates and amendments. sponsor typically must deal with each country’sregistry individually. Each registry requiresdata at slightly different points in time duringthe study and requires slightly different datasets. Trying to meet these requirements whileharmonizin