Background: Evaluation of adverse events (AE) and adverse reactions (ADR) is challenging when there is no proper observational study or monitoring data. Limited by insufficient safety data, difficulties are often encountered when determining both evidence quality in systematic reviews (SR), and levels of recommendations in guidelines. AEs/ADRs reported in literature types other than RCTs are usually ignored in intervention SRs/guidelines.
Objectives: To investigate the consistency of AEs/ADRs from the real world state monitoring data, the whole literature base and RCTs, and to see the possibility of using the later as an alternative of the former in SRs or guidelines.
Methods: Taking one patent Chinese medicine (an extraction of Cordyceps sinensis extraction, about 20 million USD marketing per year) as an example, we obtained the AEs/ADRs reported in ADR monitoring center of the State Food and Drug Administration (SFDA) of China from 2003 to 2016, and AEs/ADRs reported in the literature up to 2016 searched from PubMed, Embase, Cochrane Library, CNKI.,Wanfang data, VIP and CBM Data processing was duplicated independently and agreements were achieved. AEs/ADRs were transferred and classified according to the WHO Adverse Reaction Terminology (WHOART).
Results: 610 AE reports were found from the SFDA ADR monitoring system. ADRs suspected were 537 (88.03%). 5568 AEs were identified from 172 papers (62.79% RCTs, 13.95% case series/reports, no cohort or case-control study) with 86 ADRs (1.54%). The distribution of AEs and ADRs from whole literature base were almost the same with the monitoring system (supplement table). While, 271 AEs were identified from 108 RCTs (n=4682). ADR rate was 0.021%. AEs and ADRs reported in RCTs were significantly different from the two above data sources.
Conclusions: When AE/ADR monitoring data or large observational study is lacking or unavailable, AEs/ADRs reported in whole literature might be a better alternative than the data obtained only from RCTs for intervention SRs/guidelines.