Medicare Expenditures of Atezolizumab for a Withdrawn Accelerated Approved Indication

Abstract

This cross-sectional study examines atezolizumab as a second-line treatment for malignant urothelial carcinoma, which received accelerated US Food and Drug Administration approval, although the manufacturer’s confirmatory trial did not identify benefits.

The US Food and Drug Administration (FDA) grants accelerated approval for products that address serious or life-threatening illnesses that fill an unmet medical need¹; such products, which are initially approved using clinical surrogate end points, are then required to demonstrate clinical benefit through confirmatory trials. While the program has been praised as an important means to bring new products to market, the pathway has also been criticized as setting unacceptably low standards governing market entry or expansion.² In addition, accelerated approval raises the prospect that payers will incur expenditures for products or indications that are ultimately withdrawn. In March 2021, drug manufacturers withdrew indications for 4 oncology drugs after confirmatory trials failed to demonstrate clinical benefits.³ We quantified 2018 and 2019 US Medicare expenditures for 1 of these indications, atezolizumab as a second-line treatment for malignant urothelial carcinoma. While this indication received accelerated approval in October 2016, the manufacturer’s confirmatory trial did not identify benefits.⁴

Methods

We performed a retrospective cohort study using a 20% restricted sample of 2018 and 2019 Medicare fee-for-service (FFS) claims. This analysis was exempt from Johns Hopkins Bloomberg School of Public Health institutional review board approval because it did not constitute human participants research. We first identified Part B institutional outpatient claims using atezolizumab’s designated Healthcare Common Procedure Coding System code. Next, we used the diagnosis codes from the claims to select patients with a diagnosis of malignant urothelial carcinoma. We then identified claims in which atezolizumab was a second-line treatment based on a patient’s previous treatments for urothelial carcinoma. We replicated the algorithm to identify Part B noninstitutional outpatient claims using the carrier files. Finally, we aggregated total claim payments and beneficiaries’ coinsurance amounts.

Results

For 2018 and 2019, we found 14 182 Medicare FFS claims for atezolizumab (Table). Of these, 161 159 (8.8%) were for second-line treatment of malignant urothelial carcinoma, representing 157 unique beneficiaries. The mean (SD) Medicare payment per claim was $6854 ($1843). The mean (SD) beneficiary coinsurance per claim was $1724 ($1325). The mean (SD) total payment per claim was $8579 ($2245). Extrapolating our 20% sample to the full Medicare FFS population, we estimated in 2018 and 2019 there were approximately 6200 paid claims, representing $46 million in Medicare spending for atezolizumab for an indication with no confirmed evidence of clinical benefit.

Table. Medicare Fee-for-Service Expenditures for Atezolizumab for Withdrawn Indication.

Characteristic	Outpatient Medicare Part B
	2018	2019	2018 and 2019
Total claims, No.	5303	8879	14 182
Urothelial cancer claims, No.a	2383	2307	4690
Second-line urothelial carcinoma claims, No.b	635	606	1241
Unique beneficiaries, No.	116	76	157
Medicare payment per claim, mean (SD), $	6951 (1708)	6718 (2012)	6854 (1843)
Beneficiary coinsurance per claim, mean (SD), $c	1656 (1024)	1821 (1657)	1724 (1325)
Total payment per claim, mean (SD), $	8607 (2032)	8539 (2517)	8579 (2245)
Total Medicare payment, $d	22 067 885	15 081 655	37 149 540
Total beneficiary coinsurance, $	5 259 275	4 087 345	9346 620
Total claims payment, $	27 327 160	19 169 000	46 496 160

^a Identified using Healthcare Common Procedure Coding System diagnosis codes of C65*, C66*, C67*, or C68*.

^b Second-line claims were identified if a patient used gemcitabine, pembrolizumab, or cisplatin for urothelial carcinoma before atezolizumab use.

^c Coinsurance excludes the effect of supplemental insurance and other patient offsets.

^d Total Medicare, coinsurance, and claim payments based on 20% sample results multiplied by 5 to estimate total payments for entire Medicare Fee-for-Service.

Discussion

While the FDA’s accelerated pathway may hasten products to market, it also comes with costs borne by payers for products with indications that are ultimately withdrawn or rescinded because of lack of evidence. This study examined 1 such indication, atezolizumab as a second-line treatment for urothelial carcinoma. We found that a single payer, the US Medicare program, spent $46 million in 2018 and 2019 for this indication. We assessed only direct economic costs of drug treatment. There are other costs that individuals may have incurred, including opportunity costs of alternative, foregone treatments, and potential financial and chemical toxic effects of atezolizumab treatment. The primary limitation of our study was the use of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes listed on each Medicare claim to identify the prescribed indication of atezolizumab. The diagnosis codes reflect the patient's diagnosis but may not represent the prescribed indication of the drug.

Given that 6% of oncologic accelerated approved indications have been withdrawn,³ one could argue that this is just a cost of getting drugs to treat patients sooner. However, nearly half of accelerated approvals lack confirmatory evidence.⁵ Use of this pathway allowed the FDA to grant accelerated approval for aducanumab, which by some estimates may cost the Medicare program $29 billion annually.⁶ This raises the question as to who should bear the costs of treatments that are administered for accelerated approved indications that are ultimately withdrawn or rescinded because of a lack of confirmatory evidence. Policy options include prospective and retrospective discounts based on confirmatory trials, manufacturing plus markup pricing, or economic impact analyses to limit the exposure of payers to drugs used for indications with no confirmed benefits. In this instance, manufacturers might refund the Medicare program atezolizumab revenue that was associated with the withdrawn indication.