How should the FDA reshape the accelerated approval process?

A recent study showed that four cancer immunotherapies approved by the FDA (Accelerated Approval) were withdrawn due to invalid confirmatory trials, and Medicare spent on these invalid therapies between 2017 and 2019.
More than 224 million U.
S.
dollars
.

Because these withdrawn drugs caused taxpayers' money to be wasted, the health and pharmaceutical circles have widely questioned the FDA's accelerated approval process and called on the FDA to reform this process
.

What is accelerated approval?

Accelerated Approval (Accelerated Approval) is a method used by the FDA to accelerate the treatment of serious diseases and have significant advantages compared with existing drugs on the market, and to bring treatment to patients as soon as possible
.
In accelerated approval, the approval of the drug is usually based on the surrogate endpoint

After the accelerated approval, pharmaceutical companies still need to conduct clinical studies to confirm the expected clinical benefits
.
These studies are called Phase 4 confirmatory trials

What drugs are withdrawn?

In 2021 alone, the drugs withdrawn include Merck’s Keytruda, Bristol-Myers Squibb’s Opdivo, Roche’s Tecentriq and AstraZeneca’s Imfinzi, covering indications including bladder cancer, lung cancer, liver cancer, stomach cancer and breast cancer
.
(Note: The estimated 224 million US dollars wasted does not account for Tecentriq’s newly withdrawn drugs for the treatment of triple-negative breast cancer)

Criticism and reform

Since the initiation of the accelerated approval process in 1992, the FDA has mainly adopted biomarker-based methods to approve anti-cancer drugs, such as Tumor Response Rate (Tumor Response Rate).
These biomarkers are considered to be relatively likely to predict clinical benefit, that is, to prolong patients Life
.
As a condition for obtaining early approval, pharmaceutical manufacturers must prove the effectiveness of their drugs in confirmatory trials

Critics also criticized the FDA's slow response
.
In the absence of clear efficacy data, even after confirming the failure of the confirmatory trial, it still failed to make a timely withdrawal decision

Although criticism of accelerated approvals is nothing new, this year the problem has been sharpened by a series of withdrawn drugs
.
The Office of the Inspector General of HHS (United States Department of Health and Human Services) initiated a review of the FDA's accelerated approval process in August and is expected to issue a report in 2023

In another study in July, the researchers again suggested that the FDA should conduct further discussions on what biomarkers should be used as the basis for accelerated approval
.
One point that has received widespread support recently is that researchers believe that the FDA should finalize the confirmatory test plan as one of the conditions for accelerated approval, and negative confirmatory test data will automatically trigger the decision to withdraw the drug from the market

The researchers also recommend that Medicare & Medicaid Services and the Department of Veteran Affairs take measures to control drug costs when clinical data is incomplete, such as restricting the reimbursement of a drug Amount
.

Two researchers from the Brookings Institution and the University of Pennsylvania also made a proposal called "pay for effective drugs
.
" The proposal includes that drugmakers must provide confirmatory test results within four years, otherwise Medicare Part B will stop reimbursing

Reference source:

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Merck withdraws Keytruda from SCLC indication amid FDA crackdown

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Bristol Myers withdraws Opdivo in liver cancer as fallout from FDA meeting continues