Introduction to Current Controlled Trials (CCT) www.controlled-trials.com

1. Introduction toCurrent Controlled Trials (CCT)www.controlled-trials.com

2. What is CCT? • CCT is part of BioMed Central • The site allows users to search, register and share information about clinical trials. Access to all the information on this site is free. • Editorial Team receives, reviews, edits and publishes trial descriptive data. The resulting trials database is the ISRCTN register • Read more on the ISRCTN register here: http://bit.ly/nC1qY4

3. Trialist submits Trialist requests update CCT/ISRCTN publishes

4. ISRCTNkey dates • 2001: Medical Research Council (MRC) pilot to meet the demand for trial transparency and unique identification • 2003: ‘trialist pay’ model to ensure sustainability • 2005: ISRCTN.org is created as Not for Profit, is and administered by CCT • 2006: started adding database fields to meet requirements of international guidelines • 2007: ISRCTN data pooled into the WHO International Clinical Trials Registry Platform (WHO ICTRP) • 2010: assisted the Department of Health to launch the UK Clinical Trials Gateway (UKCTG) • 2011: increase access to trial information via lay summary • 2012: further integration with BioMed Central

5. Why register trials publicly? • Scientific, ethical, moral, legal reasons • More efficient research – avoid duplication • Improve recruitment – easier for patients and clinicians to find relevant studies • May improve quality of reporting of results • Promote transparency and collaboration • Legally mandated in USA • Required by growing number of journals since 2005 • Improve medical evidence base – reduce bias in the literature and play part in evidence-based medicine pyramid

6. Systematic reviews Randomised controlled trials Strength of evidence Non-randomised trials Cohort studies Case control studies Case series/case reports Expert opinion and ideas Evidence-based medicine pyramid

7. Avoiding reporting bias October 2010:Reboxetine is “overall an ineffective and potentially harmful antidepressant”

8. Trial ID in manuscript Abstract “...Trial registration, if your research article reports the results of a controlled health care intervention, please list your trial registry, along with the unique identifying number (e.g. Trial registration: Current Controlled Trials ISRCTN73824458). “ http://www.biomedcentral.com/bmcmed/authors/instructions/researcharticle

9. Trial ID

10. Trial ID

11. ISRCTN benefits • Open to all countries, all areas of healthcare & all study designs • Allows registration of trials at any stage • Unlimited updates to the trial record to ensure accuracy & completeness • Quick publication of trial details • Opportunity to include plain English summaries • Links to resulting publications • Data provider to the WHO International Clinical Trials Registry Platform (WHO ICTRP) • Close collaboration with the Department of Health – UK trials pooled into the UK Clinical Trials Gateway (UKCTG) • Incentives for publication in selected BioMed Central journals

12. What do we want CCT to be? “A sustainable, citable, freely accessible and continuously updated database of clinical research studies – whether proposed, ongoing or completed – increasing research transparency, efficiency and reliability of evidence, and offering additional services to help ensure the successful completion and communication of all study outcomes.” Registering a study with CCT should be the first logical step in disseminating research with BioMed Central. Until journal publication CCT is the go-to resource for trial information and is part of the Threaded Publication concept

13. Threaded Publication Vision TrialRegistration Number Secondary analysis • All publications about a trial and linked together in a thread • Across publishers Results Future publications Protocol

14. Low transparency Study registration inTrial Register e.g. ISRCTN Study protocol Protocol or other updates Potential for bias Publication e.g. in BioMed Central Methodology articles First report of study findings Secondary analysis Longer-term follow-up Lessons learned Systematic reviews and meta-analysis Raw data deposition and sharing High transparency

15. How does it work? • Hyperlinks between trial registration records and trial protocol/results – or any other article including the trial ID in the abstract • Article types and journals and editorial policies that enable publication of all clinical trial-related publications • Financial incentives for authors, and institutions, who ultimately often fund publication, to complete the scientific record • We are working with CrossRef to develop CrossMark for threaded publications pan-publisher via the DOI system

16. CCT/ISRCTN partners • The Department of Health and the NIHR Portfolio Database– adoption by the Portfolio ensures that trials can benefit from NHS support and the Portfolio sends trial data batches on behalf of researchers who have opted for ISRCTN public registration. • The Medical Research Council and the Wellcome Trust advocate trial registration. • The Integrated Research Application System – improved guidance regarding plain English summaries will ensure that researchers produce material once that can then be re-used at different stages, including ISRCTN trial registration. • INVOLVE - advises on how to increase participants’ involvement in research through better written documents. • Association of Medical Research Charities – have reported on challenges to communicate existence and results of research in plain English. • WHO ICTRP search portal– ISRCTN data uploaded weekly. • UK Clinical Trials Gateway– ISRCTN data uploaded daily. • ISRCTN follows the development of all publicly available registers through its participation to the WHO Working Group on Best Practice for Clinical Trials Registers, in particularClinicalTrials.gov (its UK trials are also pooled in the UK Clinical Trials Gateway) and the European Trials Register (public side of EudraCT).