For the US withdrawal from Afghanistan, the decision to withdraw from two decades of war is the right decision and welcomed by the majority of the Americans. However, the execution of the withdrawal was a disaster. The execution of the withdrawal is not properly planned, botched, entirely a failure no matter how the Biden administration tries to spin and change the subject. When questioned by the reporters, the Biden administration keeps mentioning how correct the decision of withdrawal from Afghanistan is and avoids mentioning why the execution of the withdrawal goes so wrong.
- Afghanistan is much worse than the fall of Saigon. Biden needs to act like it
- Biden dodged duty when he left Bagram, and then he dodged the question about it
- Leaving Afghanistan Was the Right Call, But It May Haunt Biden—and the U.S.—Forever
- Even Biden allies question execution of Afghanistan withdrawal
- Jake Tapper: On Afghanistan, Biden “Keeps Trying To Change The Subject From This Inept Withdrawal”
Changing the subject is also the theme in the controversial approval of Aduhelm for the treatment of Alzheimer's disease through the 'accelerated approval' pathway. The full story of the Aduhelm approval is very well captured in a New York Times article "How an Unproven Alzheimer's Drug Got Approved" and NEJM Interview: Dr. Gil Rabinovici on the FDA’s controversial approval of a new treatment for Alzheimer’s disease. on Apple Podcasts.
'Accelerated approval' is a valid pathway for approving a drug based on the surrogate endpoint without waiting for the results from the lengthy confirmatory trial to demonstrate the clinical benefit. "Accelerated approval" was one of the regulatory approval pathways listed in FDA's guidance for industry "Expedited Programs for SeriousConditions – Drugs and Biologics"
Facing the mounting criticisms, FDA officials published the papers to defend their decision - Approval of Aduhelm through the 'accelerated approval' pathway is the right decision. They changed the subject here. Rather than arguing if approval of Aduhelm is the right decision, they argued if 'accelerated approval' is an appropriate approval pathway.
- An Appropriate Use of Accelerated Approval — Aducanumab for Alzheimer’s Disease
- Approval of Aducanumab for Alzheimer Disease—the FDA’s Perspective
The controversy is not about 'accelerated approval', it is about how the 'accelerated approval' is used in the approval of Aduhelm.
Accelerated approval is appropriate if the following qualifying criteria are met:
- Serious Condition
- Meaningful Advantage Over Available Therapy
- Demonstrates an Effect on an Endpoint That Is Reasonably Likely to Predict Clinical Benefit
In Aduhelm's situation, the third criterion was not met. The two confirmatory trials had already been completed and indicated the inclusive results in clinical benefit. There is no evidence to conclude the biomarker (beta-amyloid) will be 'reasonably likely to predict clinical benefit.'
'Accelerated approval' is a valid pathway for drug approval for a serious condition, however, it can't be applied to a drug approval:
- as a remedy approach (when clinical benefit had been shown to be inclusive)
- retrospectively applied (when the lengthy confirmatory trials had already been completed)
- against the pre-specification rule (i.e., accelerated approval pathway had been discussed and agreed with the agency prior to the BLA/NDA submission)
- for pivotal studies that had been discontinued early due to futility
- based on results largely from the post-hoc, sub-group analyses
- against the consensus objection from the FDA advisory committee members.
The New York Times (9/2, Belluck) reports two congressional committees “investigating the controversial federal approval of Biogen’s Alzheimer’s drug, Aduhelm [aducanumab], demanded extensive information and documents from the Food and Drug Administration in a letter released on Thursday, making it clear that the committees’ leaders are troubled by unusual actions the agency took in the course of evaluating and approving the drug.” The letter said the agency “granted accelerated approval for the drug despite concerns raised by experts – including the agency’s own staff’ and members of its independent advisory committee. ... We are also concerned by reports of unusual coordination between F.D.A. and Biogen throughout the drug’s approval process.” The Times adds, “While some Alzheimer’s experts did support the approval, given that there are so few therapies available for the devastating condition, many are concerned that the evidence does not convincingly show the drug can provide any benefit. There is also concern because the medication can cause brain swelling or brain bleeding.”
Afgan Withdrawal: the decision is right, execution is not!
Aduhelm Approval: accelerated approval is a valid pathway, the application of accelerated approval in Aduheml approval is not!
