gms | German Medical Science

Background and aim: In clinical trials as well as in pharmacovigilance safety issues have to be reported to the pharmaceutical manufacturer and competent authorities. In clinical trials furthermore reports have to be sent to the competent ethics committees. The adherence to the Guidelines for reporting safety issues in clinical trials is analyzed from the routine work point of view.

Material and method: The usefulness of safety reports SUSAR (suspected unexpected serious adverse reactions) reports and DSUR (developmental safety update reports) and the adherence to the corresponding guidelines was analyzed on the basis of the daily workload due to incoming safety reports in an ethics committee (Ethics committee of the Medical Faculty of the Technische Universität Dresden).

Results: SUSAR reports not in adherence with the guidelines are the majority of all SUSAR reports received. In many cases even simple formal requirements are violated (reporting of events occurring in conjunction with blinded trial medication without decoding, double and triple reporting of single events, reporting of events well established in SMPC or investigators brochure (e.g. bleeding in patients treated with a combination of Clopidogrel, ASA, Heparin and factor Xa), update reports sent in conjunction with initial reports, etc.). Additionally data quality is in many cases so poor (unknown indication, unknown concomitant medication, cases that the reporting physician has not treated, unknown age and sex, male patients treated for ovarian cancer, etc.) that no evaluation is possible. Furthermore in many cases events due to the condition treated are reported as SUSAR (e.g. bone pain in trials in patients with multiple myeloma, DVT in patients in trials of factor Xa inhibitors, infection in trials in patients with leukemia).

DSUR reports are only supplied for some part of the running clinical trials and are of very different quality from poor [line listing of previously sent SUSAR’s without any useful comment] to excellent (statistical evaluation of decoded treatment groups with a profound evaluation and discussion of preclinical and previous clinical data to identify or annihilate potential safety concerns).

Conclusions: As reported previously for a limited sample (Trillenberg et al., 10. VKliPha, 85% of SUSAR reports are not according to reporting requirements) the quality and adherence to the relevant guidelines is inadequate in the vast majority of SUSAR reports sent to ethics committees. A similar situation applies to DSUR reporting.

Great efforts are necessary to streamline the reporting of safety information in clinical trials and to optimize the perceptibility of safety risks during clinical development. The actual way to spread all information – relevant or not; verifiable or rumor – to everyone involved is neither adequate to attract attention to risks nor cost effective for the pharmaceutical industry.