Critical Analysis: Dr. Vinay Prasad Takes on the ADAURA Trial's Ethical Concerns

Overview

In a compelling critique of the ADAURA trial, Dr. Vinay Prasad raised serious ethical and methodological concerns about AstraZeneca's study of adjuvant osimertinib in resected EGFR-mutant non-small cell lung cancer. His analysis reveals fundamental flaws that challenge the trial's conclusions and ethical standing. 

Top 10 Critical Quotes from Dr. Prasad

1. "The trial has inadequate staging... If you can afford $440,000 of osimertinib per person... you tell me you can't afford the brain MRI?"
2. "38.5% is shitty... if your mother or father were on the control arm, you want them to have a 100% chance of getting osimertinib when they have Progressive disease."
3. "This trial does not benefit the citizens of America because the control arm is not reflective of the practice in America."
4. "It's exploiting people in some parts of the world who cannot afford osimertinib to justify the routine application to people in other parts of the world who have the money."
5. "DFS is not a validated surrogate for OS in lung cancer with targeted therapies."
6. "The IRB should not have allowed this to be upon request; it should have been mandatory to tell them when they had progression."
7. "To withhold this information from trial participants makes me sick."
8. "The trial is ethically debunked... it's a fraud... it's a great crime that had happened."
9. "You couldn't advocate for your patients on the control arm... and now you want to advocate for the world? Give me a break."
10. "When the history book is written 50 years from now, this trial is going to be in the same chapter with the lobotomy guy."
    

Key Criticisms

Methodological Flaws

• Inadequate staging (no mandatory brain MRI or PET-CT)
• Insufficient adjuvant chemotherapy requirements
• Disease-free survival (DFS) inappropriately used as a surrogate endpoint
• Poor control arm management

  Video Clip - Discussion of the staging of the ADAURA Trial from Dr. Prasad's 2023 video discussion

Ethical Concerns

• Only 38.5% of control arm patients who progressed received osimertinib
• Exploitation of resource-poor countries
• Failure to mandate unblinding upon progression
• Withholding of critical treatment information from patients

Video Clip - Discussion of the Study's Crossover Policy to osimertinib by Dr. Prasad

Cost and Access Issues

• $440,000 per course of treatment
• $960,000 to avert a single DFS event
• Trial results don't help either wealthy or resource-poor nations
• Cost-effectiveness concerns even in rich nations
  

  Video Clip - Dr. Prasad discusses how ADAURA was exploitive to game the US regulatory system

  
  

Implications for Practice

Dr. Prasad argues that oncologists should:

• Question the validity of the trial's conclusions
• Consider the ethical implications of similar trial designs
• Advocate for proper control arm treatment in clinical trials
• Prioritize patient care over industry interests

Conclusion

The ADAURA trial, despite its celebrated status  at #ASCO23, was described by Dr. Prasad as an example of "moral rot" in oncology. His analysis suggests that the oncology community needs to critically examine how clinical trials are conducted, particularly regarding ethical treatment of control arm patients and global healthcare disparities.

Video Clip - Peer Discussion with Dr. Jack West

Watch Dr. Jack West, currently with Summit Therapeutics,  discuss the ADAURA trial and Lung Cancer clinical trial ethics with Dr. Prasad from a 2022 video discussion.