OBJECTIVES : The full extent of scientific misconduct including data fraud in clinical trials will, by its nature, never be known. In the highly regulated world of controlled clinical trials, misconduct is identified, and studies discounted from regulatory filings as a result. However, this does not necessarily correspond to the peer-reviewed literature. We briefly review the process for identifying and retracting fraudulent studies and these ease of access to such information. We used a case study of thromboprophylaxis after total knee arthroplasty (TKA) in which RECORD-4, was identified by the FDA as unreliable due to scientific misconduct and excluded from the FDA (and EMA) label. We demonstrate how inclusion of fraudulent studies can impact SLRs, and network meta-analysis (NMA). A series of recommendations to identify fraudulent studies are added to the systematic reviewer’s toolbox.

METHODS : A targeted review was conducted in PubMed to identify SLRs with meta-analyses or NMAs of RCTs including patients treated for thromboprophylaxis following TKA or total hip arthroplasty (THA). Peer-reviewed correspondence associated with RECORD-4 and FDA and EMA documentation was reviewed to determine how transparent the issues with RECORD-4 are in the public domain.

RESULTS : Our review returned 38 references; data was extracted from 14 SLRs published between 2010-2019. All 14 SLRs included the RECORD-4 study, despite its unreliability being confirmed by the FDA in 2011. The primary RECORD-4 publication remains unretracted and associated correspondence to the pivotal publication does not mention any of the issues highlighted by the FDA. In early filings to the FDA, RECORD-4 is included whereas the final filing, and FDA and EMA labels do not mention RECORD-4.

CONCLUSIONS : Improved transparency and communication are required to ensure studies found to involve scientific misconduct can be more easily recognised. In lieu of this more rigorous search burden is placed on the systematic reviewer.