23 Dec Patient-Relevant Research Outcomes from Published vs Non-Published Data

Medical Research.com Interview with:
Dr. Beate Wieseler

Head of Department Dept. Drug Assessment
Institute for Quality and Efficiency 
in Health Care (IQWiG)
Im Mediapark
Köln Germany

MedicalResearch.com: What are the main findings of the study?

Dr. Wieseler: Our study shows that unpublished clinical study reports, i.e. reports submitted to regulatory authorities during the approval procedure for a drug, provide substantially more information on patient-relevant outcomes than publicly available sources, i.e. articles published in medical journals and reports published in online clinical trial registries. (A “patient-relevant outcome” is an outcome describing morbidity, mortality or health-related quality of life.)
In detail, we analysed 101 trials with clinical study reports; 86 trials had at least one publicly available source, 65 at least one journal publication, and 50 a registry report. The trials included 1,080 patient-relevant outcomes. The clinical study reports provided complete information on a considerably higher proportion of patient-relevant outcomes (86%) than the combined publicly available sources (39%). With the exception of health-related quality of life (57%), clinical study reports provided complete information on 78% to 100% of the various benefit outcomes (combined publicly available sources: 20% to 53%). They also provided considerably more information on harms. The differences in completeness of information for patient-relevant outcomes between clinical study reports and journal publications or registry reports (or a combination of both) were statistically significant for all types of outcomes [1].

References

1. Wieseler B, Wolfram N, McGauran N, Kerekes MF, Vervölgyi V, Kohlepp P, et al. Completeness of Reporting of Patient-Relevant Clinical Trial Outcomes: Comparison of Unpublished Clinical Study Reports with Publicly Available Data. PLoS Med. 2013 349 Oct 8;10(10):e1001526

MedicalResearch.com: Were any of the findings unexpected?

Dr. Wieseler: Previous research on the antidepressant reboxetine and the antiviral oseltamivir (Tamiflu) showed that inclusion of unpublished data from clinical study reports changed previous conclusions about the benefits and harms of these drugs [1,2]. Our previous study on the issue of information gain from clinical study reports showed that this document type provided substantially more information on study methods and selected study outcomes (primary outcomes and adverse events) [3]. We therefore expected similar results in our current study. However, in our current study, the information gain from clinical study reports was even greater for patient-relevant outcomes (regardless of whether primary or not): While in the previous study the proportion of completely reported primary outcomes and adverse events was 91% for clinical study reports, 52% for journal publications, and 71% for registry reports, the corresponding values for the full range of (primary and non-primary) patient-relevant outcomes investigated in the current study were 86%, 23%, and 22%, respectively [3,4].

References

1. Doshi P, Jefferson T, Del Mar C (2012) The imperative to share clinical study reports: recommendations from the Tamiflu experience. PLoS Med 9: e1001201 doi:10.1371/journal.pmed.1001201.
2. Eyding D, Lelgemann M, Grouven U, Harter M, Kromp M, et al. (2010) Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials. BMJ 341: c4737.
3. Wieseler B, Kerekes MF, Vervoelgyi V, McGauran N, Kaiser T (2012) Impact of document type on reporting quality of clinical drug trials: a comparison of registry reports, clinical study reports, and journal publications. BMJ 344: d8141
4. Wieseler B, Wolfram N, McGauran N, Kerekes MF, Vervölgyi V, Kohlepp P, et al. Completeness of Reporting of Patient-Relevant Clinical Trial Outcomes: Comparison of Unpublished Clinical Study Reports with Publicly Available Data. PLoS Med. 2013 349 Oct 8;10(10):e1001526

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Wieseler: Clinicians and patients should be aware that information obtained from published evidence alone may be biased. For instance, the benefits of a drug may be exaggerated and harms may be underestimated.

Clinical study reports should be made publicly available as they may substantially influence conclusions concerning the actual position of an individual drug in a therapeutic area.

MedicalResearch.com: What[NMG1]  recommendations do you have for future research as a result of this study?

Dr. Wieseler: Future research could include a more detailed comparison of information reported in unpublished clinical study reports and information reported in journal publications to further investigate the reasons for selective reporting (“outcome reporting bias”).

Citation:

Completeness of Reporting of Patient-Relevant Clinical Trial Outcomes: Comparison of Unpublished Clinical Study Reports with Publicly Available Data  

Beate Wieseler, Natalia Wolfram, Natalie McGauran, Michaela F. Kerekes, Volker Vervölgyi, Petra Kohlepp, Marloes Kamphuis, Ulrich Grouven

Published: October 08, 2013
DOI: 10.1371/journal.pmed.1001526

Last Updated on February 2, 2014 by Marie Benz MD FAAD