Searching for evidence – Trial registries and how to use them efficiently
About the author
Prof. Matthias P. Schönermark, M.D., Ph.D.
Founder and Managing Director
Founder and Managing Director
Fon: +49 511 64 68 14 – 0
Fax: +49 511 64 68 14 18
Fax: +49 511 64 68 14 18
To approach this question the IQWiG tested three different trial registries for the (complete) availability of randomized controlled trials (RCTs) on new drugs and developed such as tested registry specific search strategies. As a result, searching in the trial registry ‘Clinical Trials.gov’ (CT.gov) turned out to be highly sensitive with a hit ratio of 94-100%, even when only single search terms (generic drug name and reasonably-derived condition-related search term) were applied. For an intervention-related search in the trial registries ‘EU Clinical Trial Registry (EU-CTR)’ and ‘International Clinical Trials Registry Platform’ (ICTPR), in contrast, both the generic drug name and the drug code should be used. Likewise, condition-related searches in EU-CTR and ICTPR should include several search terms. All in all, in comparison to the other registries CT.gov convinced by the complexity of the available entries and the simplicity of the required search strategy.
For its analysis the IQWiG referred to a reference pool of dossiers published between 2011 and 2014. Thereof, the IQWiG extracted trial registry entries of all contained RTCs. The analysis, however, was first published in 2017. Hence, it is questionable whether the RCTs were registered yet at the time of dossier compilation- as a constant update of the entries is clearly conducive for the efficient preparation of a dossier.
Here, a statutory duty for registration would accommodate an efficient search. According to the legislation amendment FDAAA 801, in the US a public registration is yet obligatory for certain drugs – which most likely had a positive impact on the high success rates of the IQWiG test. In Germany, conversely, there is currently no legal obligation for a registration in a public registry. According to the GCP regulation solely the registration in the EU registry EudraCT is statutory. Numerous funding institutions or publishers, however, demand a public registration for funding or publication.
In addition to registry searches the detailed investigation of bibliographic databases is mandatory for the preparation of an AMNOG dossier and, besides screening internal documents of the pharmaceutical company, essential to examine not only the integrity of the clinical studies but also the validity of their evidence.
The dossier forms the foundation for the benefit assessment of the AMNOG-procedure. In doing so, dossiers should not only fulfill formal requirements, but also describe the whole value story of the product. At SKC Beratungsgesellschaft, we define a value story as the central strategical brick for a successful market access, because it describes the story of the (additional) value of a certain product. Please find more information at our service portfolio.
BY Prof. Matthias P. Schönermark, M.D., Ph.D., Founder and Managing Director of SKC Beratungsgesellschaft mbH and Dr. rer. nat. Anja Baigger, SKC Beratungsgesellschaft mbH
Sources:
Knelangen et al. (2017) Trial registry searches for randomized controlled trials of new drugs required registry-specific adaptation to achieve adequate sensitivity. Journal of Clinical Epidemiology 94 (201) 69-75
Section 801 of the Food and Drug Administration Amendments Act
FAQs Deutscher Register Klinischer Studien (German only)
DFG: Merkblatt “Programm klinische Studien” (German only)
International Commitee of Medical Journal Editors - Publishing Issues: Clinical Trials