Research conducted into this question relating to the ClinicalTrials.gov database and the International Clinical Trials Registry Platform will be reported.

1. Is it appropriate to limit
searches to prospective
trials registries?
Research evidence
Julie Glanville
Associate Director, YHEC, University of York, York, UK
Co-Convenor, Cochrane IRMG
julie.glanville@york.ac.uk
Oct 2015

2. Overview
 Report on pilot study and follow-up research undertaken
at York Health Economics Consortium
 Can we rely on searches of trials registers to find all
relevant studies for assessment for a SR?
 Acknowledgements:
– Karen Hall for initial ideas and involvement in the pilot study
– My co-authors: Steven Duffy, Rachael McCool and Danielle
Varley

3. Background
 Trials registers are growing in number and currency
 Legislation, journal editors, consumer pressure and other factors
are providing the impetus to increase prospective registration of
trials
 Have we reached the stage where we can identify RCTs for reviews
from the registers alone?
 Generated two questions:
 Can we dispense with the bibliographic searches of databases such
as Medline and Embase?
 Do we need to search both ClinicalTrials.gov and the ICTRP portal
to find trial records (given that the content of one is included in the
other)?

4. Research project
 Pilot study with 2 recently updated Cochrane reviews
 Larger study with 6 further reviews

5. Methods
Identify Gold
standard
• Identified eight recently updated Cochrane Reviews
• Identified included studies in those reviews which had matching trials
records in ICTRP and/or ClinicalTrials.gov
Test strategies
• Reran or adapted the systematic review search strategies to find the
identified studies in each register
• Tested different search approaches
Assess strategy
yield
• Identified yield of search approaches in ICTRP and/or
ClinicalTrials.gov
• Explored the value of using basic and advanced search options in
those registers

6. Identifying candidate SRs
 Pilot study [2011]:
 two recently updated systematic reviews from the
Cochrane Injuries Group
 Larger study [2012]:
 searching for ‘‘New’’ reviews in the 2012 issue 1
version of CDSR

7. Identifying records in trials
registers, 1
 We used the following techniques to search ICTRP
and/or ClinicalTrials.gov to identify known trials
 Trial number identifier
OR
 Trial name/abbreviation
OR
 Intervention (AND (geographical location OR date) where result
numbers were large)
OR
 Author/lead investigator (AND (geographical location OR date)
where result numbers were large)

8. Identifying records in trials
registers, 2
 To achieve geographical focus
 ‘‘Locations’’ field was used in ClinicalTrials.gov
 “Countries of recruitment’’ option was used in ICTRP
 If the included study was carried out in the United States
and the search results were large, the ‘‘State’’ location
limit in ClinicalTrials.gov was employed.

9. Results, selected SRs
 Anti-fibrinolytic use for minimising perioperative allogeneic blood
transfusion
 Preoperative autologous donation for minimising perioperative allogeneic
blood transfusion
 Parenteral versus oral iron therapy for adults and children with chronic
kidney disease
 Intracutaneous or subcutaneous sterile water injection compared with
blinded controls for pain management in labour
 Intramedullary nailing for tibial shaft fractures in adults
 Tranexamic acid for upper gastrointestinal bleeding
 Intravesical gemcitabine for non-muscle invasive bladder cancer
 Continuous glucose monitoring systems for type 1 diabetes mellitus

10. Results: study identification
Number
of
included
studies
included
studies
identified in
ClinicalTrials.
gov
included
studies
identified in
ICTRP
Number of
identified studies
not found in
either resource
Overlap
between
CT and
ICTRP
Henry 1 252 4 8 244 4
Henry 2 14 1 1 13 1
Albaramk
i
28 5 6 22 5
Derry 7 0 0 7 0
Duan 11 1 1 10 1
Gluud 7 0 0 7 0
Jones 6 2 2 4 2
Langend
am
22 8 12 10 8
Number of Included Studies Identified in the Trials Registers

11.  Reviews varied in size from 6 to 252 included studies
 30 of the 347 (8.6%) included studies were in one of the two
registers
 2/8 reviews (both 7 studies) had no matching trial records in
either ClinicalTrials.gov or ICTRP
 The percentage of included studies found in registers ranged
from 0% (2 reviews) to 54.5% (1 review)
Identified Studies

12. Trial age?
 Was identification a feature of register age?
 SR Example 1
 18/22 of the studies in the SR were published after 2005 (so
might have been expected to be registered)
 12/18 (66.6%) were identified in the registers
 SR example 2
 206 studies were published after 2005
 8/206 (3.88%) were identified in the registers

13. Discussion
 Matching included studies to register records
can be challenging
 We may have missed a few
 Trials registers are complementary to
bibliographic databases and help to
 Fill the gaps
 Provide results (and different views on results)
 Provide access to trials which may never be formally
published

14. Other research, snapshots
 Reveiz L (Colloquium 2011)
 89/256 trials (16.9%) identified were registered in ICTRP
 Stegeman I et al (Colloquium 2014)
 “clinical trial registration is not yet adopted in otolarynchology”
 Hardt J Ls (Colloquium 2013)
 83% of relevant surgical RCTs were registered
 Bhaumik et al (Colloquium 2015)
 63/686 (9%) of trials reported in Indian journals were registered
 Scherer (BMC Medical Res Methodology 2013)
 154/496 (31%) ARVO abstracts had a trial register record
 Odutayo A et al (Colloquium 2014)
 560/1370 (40.9%) RCTs from Pubmed were reported as registered

15. Other research (snapshot)
 Li (Colloquium 2012)
 Japan, South Korea, Singapore, Hong Kong and Taiwan: all countries
had less than 30% of trials on Pubmed, registered
 Hooft L et al (Colloquium 2011)
 172 Dutch pediatric drug trials – 56% were registered prospectively.
 Huser V & Cimino J J. JAMIA 2013;20(e1)
 661/690 5 ICJME founding journals included the trial id
 Gill C J. BMJ Open 2012; 2(4)
 “This analysis indicates that compliance with registration of US-based
human subject research trials on CTG remains quite poor. ”
 Kohler M et al. BMJ 2015 350:h796
 15 IQWIG dossiers (up to 28 Feb 2013) containing 22 studies
 A registry report in ClinicaTrials.gov was available for all studies

16. Summary
 Clinicaltrials.gov and ICTRP
 These are valuable major resources available to identify clinical
trials
 The evidence from our research suggests that low proportions of
trials included in SRs have trial records, even when focusing on
more recent trials
 We still need to search both bibliographic databases and trials
registers until we can be sure that trials are being prospectively
registered on the trials registers
 Current evidence suggests we need to search both
ClinicalTrials.gov and ICTRP because of interface differences

17. Our publication
 Glanville JM, Duffy S, McCool R, Varley D.
 Searching ClinicalTrials.gov and the International
Clinical Trials Registry Platform to inform systematic
reviews: what are the optimal search approaches?
 J Med Libr Assoc. 2014 Jul;102(3):177-83.
 doi: 10.3163/1536-5050.102.3.007

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Thank you
julie.glanville@york.ac.uk
Telephone: +44 1904 324832
Website: www.yhec.co.uk