Several drugs gained market authorization based on the demonstration of improved progression-free survival (PFS), adopted as a primary endpoint in Phase 3 clinical trials. In addition, an increasing number of drugs have been granted accelerated approval, and sometimes regular approval, by the main regulatory agencies based on the evaluation of the overall response rate in Phase 1 and 2 clinical trials. However, while the overall survival is an unbiased measure of drug efficacy, these outcomes rely on the assessment of radiological images and patients' categorization using standardized response criteria. The evaluation of these outcomes may be influenced by subjective factors, particularly when the analysis is performed locally. In fact, blinding of treatment is not always possible in modern oncology trials. Therefore, a blinded independent central review is often adopted to overcome the problem of expectation bias associated with local investigator assessments. In this regard, we have recently observed that local investigators tend to overestimate the overall response rate in comparison to central reviewers in Phase 2 clinical trials, whereas we did not find any significant evaluation bias between local investigators and central reviews when considering progression-free survival in both Phase 2 and 3 trials. In the present article, we have tried to understand the reasons behind this discrepancy by reviewing the available evidence in the literature. In addition, a further analysis of Phase 2 and 3 clinical trials that included the evaluation of both endpoints showed that local investigators significantly overestimate overall response rates compared to blinded independent central reviews in uncontrolled oncology trials.

Dello Russo, C., Navarra, P., Local Investigators Significantly Overestimate Overall Response Rates Compared to Blinded Independent Central Reviews in Uncontrolled Oncology Trials: A Comprehensive Review of the Literature, <<FRONTIERS IN PHARMACOLOGY>>, 2022; (13 / 858354): 1-17. [doi:10.3389/fphar.2022.858354] [http://hdl.handle.net/10807/210463]

Local Investigators Significantly Overestimate Overall Response Rates Compared to Blinded Independent Central Reviews in Uncontrolled Oncology Trials: A Comprehensive Review of the Literature

Dello Russo, Cinzia;Navarra, Pierluigi
2022

Abstract

Several drugs gained market authorization based on the demonstration of improved progression-free survival (PFS), adopted as a primary endpoint in Phase 3 clinical trials. In addition, an increasing number of drugs have been granted accelerated approval, and sometimes regular approval, by the main regulatory agencies based on the evaluation of the overall response rate in Phase 1 and 2 clinical trials. However, while the overall survival is an unbiased measure of drug efficacy, these outcomes rely on the assessment of radiological images and patients' categorization using standardized response criteria. The evaluation of these outcomes may be influenced by subjective factors, particularly when the analysis is performed locally. In fact, blinding of treatment is not always possible in modern oncology trials. Therefore, a blinded independent central review is often adopted to overcome the problem of expectation bias associated with local investigator assessments. In this regard, we have recently observed that local investigators tend to overestimate the overall response rate in comparison to central reviewers in Phase 2 clinical trials, whereas we did not find any significant evaluation bias between local investigators and central reviews when considering progression-free survival in both Phase 2 and 3 trials. In the present article, we have tried to understand the reasons behind this discrepancy by reviewing the available evidence in the literature. In addition, a further analysis of Phase 2 and 3 clinical trials that included the evaluation of both endpoints showed that local investigators significantly overestimate overall response rates compared to blinded independent central reviews in uncontrolled oncology trials.
Inglese
Dello Russo, C., Navarra, P., Local Investigators Significantly Overestimate Overall Response Rates Compared to Blinded Independent Central Reviews in Uncontrolled Oncology Trials: A Comprehensive Review of the Literature, <<FRONTIERS IN PHARMACOLOGY>>, 2022; (13 / 858354): 1-17. [doi:10.3389/fphar.2022.858354] [http://hdl.handle.net/10807/210463]
File in questo prodotto:
File Dimensione Formato  
2022 Frontiers in Pharmacol -DelloRusso & Navarra.pdf

accesso aperto

Tipologia file ?: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 733.33 kB
Formato Adobe PDF
733.33 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/210463
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 0
social impact