Clinical Trials of Solid Tumor Drugs Approved in Europe: Evidence-Based-Medicine

Pharmaceutical Science-Pharmacy For Better Health

Abstract

The Response Evaluation Criteria in Solid Tumors (RECIST) were introduced to determine response to therapy by evaluation  of  change from baseline  while  on the treatment  of  the solid  tumor. These criteria  are used mainly in clinical trials where tumor objective response (tumor shrinkage) or disease progression is the primary endpoint. RECIST is widely  used by academic institutions, cooperative groups, and industry for oncology clinical  trials. Regulatory authorities use RECIST as an appropriate  guideline for  risk-benefit  assessments of  oncology  drugs. This  study aimed  to assess the impact  on pivotal  clinical trial  designs  due  to  adopting  the  RECIST  for  assessing the  risk-benefit  ratio  for  oncology  drugs approved  in  Europe  for treatment of solid tumors (2000–2019). The Summary of Product Characteristics for all oncology drugs was reviewed to identify the  pivotal  clinical  trials.  Results:  There  were  78  pivotal  clinical  trials  for  38  oncology  drugs approved, by the  European Medicines Agency (EMA), for treatment  of solid tumors. Open-label randomized controlled trials (RCTs) account for 62.82% of the pivotal clinical trials compared to 37.18% blinded RCTs. A total of 6,721 patients (average=1,120) participated in 78 pivotal clinical trials. Around sixty-three percent (4,211 out of 6,721) of patients participated in blinded RCTs, and 37.34% (2,510 out of 6,721) of patients participated in open-label RCTs. Conclusion: Less restrictive rules for oncology drugs approval were applied by the regulatory  agency. Over  19 years, EMA had approved oncology  drugs based on open-label  trials,  especially when an oncology drug was compared to an active comparator, with results of few or no clinical improvement over existing therapy. The approval process of oncology drugs should be supported by clear evidence about the clinical effects of the new oncology drugs compared to the existing effective oncology therapies using clinical trial designs that are methodologically rigorous.