PONE-D-22-01674Cost-utility analysis of adding abiraterone acetate plus prednisone/prednisolone to long-term hormone therapy in newly diagnosed advanced prostate cancer in England: lifetime decision model based on STAMPEDE trial dataPLOS ONE

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Thank you for stating the following in the Competing Interests section: [Besides the funding declared above,• CDB reports grants from Novartis, Sanofi-Aventis, Pfizer, Janssen Pharma, Cancer Research UK, and Medical Research Council.• DD reports personal fees from The Institute of Cancer Research, grants from Cancer Research UK Program Grant and personal fees from Janssen. In addition, DD has a patent EP1933709B1 issued.• GA reports receiving commercial research grants from Janssen and AstraZeneca; has received honoraria and/or travel support from the speakers’ bureaus of Janssen, Astellas, Pfizer, Ferring, Sanofi-Aventis and Roche/Ventana; and has served as a consultant for/advisory board member of Janssen, Bayer, Astellas, Pfizer, Novartis, AstraZeneca, Orion, and Essa. GA has an ownership interest (including patents) in The Institute of Cancer Research Rewards to Discoverers for abiraterone acetate. • RJJ reports grants and personal fees from Astellas, AstraZeneca, Exelixis, and Roche; grants, personal fees and non-financial support from Bayer; personal fees and non-financial support from Bristol Myers Squibb, Janssen, Ipsen, and MSD; and personal fees from Merck Serono, Novartis, Pfizer, Sanofi Genzyme, and EUSA.• WC reports grants from Myriad Genetics.• CP reports personal fees from Bayer, Clarity, ITM (Isotopen Technologien Muenchen AG), Janssen, and Myovant.• SG reports personal fees from Sanofi, Orion, Roche, Janssen Cilag, and Amgen; other benefits from Menarini Silicon Biosystems, Bayer, AAA International, ProteoMediX, Toledo, and MSD; personal fees and other benefits from Astellas Pharma; and grants from Astellas Pharma.• ZM reports involvement in consultancy and advisory boards at Janssen and Sanofi, in advisory boards at Astellas, and sponsorship to attend medical conferences from Astellas, Bayer and Janssen.• NWC reports receiving research grants AstraZeneca and Janssen; honoraria and/or travel support from the speakers’ bureaus of Janssen, Astellas, Ferring, Sanofi-Aventis and has served as a consultant for/advisory board member of Janssen, Bayer, Astellas, Ferring, and AstraZeneca. • MKBP reports unrestricted grant funding to contribute to STAMPEDE overall from Astellas, Clovis Oncology, Novartis, Pfizer and Sanofi.• MRS reports grants from Clovis, grants and non-financial support from Astellas, Janssen, Novartis, Pfizer, and Sanofi to support the running of STAMPEDE; and personal fees from Lilly Oncology and Janssen for educational events unconnected to the submitted work or the underpinning trial.• NDJ reports grants and personal fees from Janssen, Astellas, and Sanofi, and personal fees from AstraZeneca, during the conduct of the study.• CSC, RMH, AG, FCI, DM, HLR, JMR, RM, JFL and JW have nothing to disclose.]  Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: "This does not alter our adherence to  PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests).  If there are restrictions on sharing of data and/or materials, please state these. 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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: The authors present results of a cost-utility analysis of adding abiraterone acetate and prednisone or prednisolone (AAP) to long-term hormone therapy in men newly diagnosed with advanced prostate cancer. They created a simulation model to simulate time in various states based on STAMPEDE trial data. This information was then used in combination with lifetime costs and quality adjusted life years also estimated using trial data, along with data from the literature when needed to assess the cost-effectiveness of the treatment. Authors concluded that AAP was not cost-effective at the current estimated cost, but also present scenarios where it could be cost-effective. Authors provide detailed explanations of the methods used (and results to support decisions in supplemental material). There are a couple of minor comments that authors should address.

1. on page 8, authors state that the dose information for abiraterone in the SOC-only arm was missing and imputed as the indicated and modal observed amount. Was this for those individuals that later took AAP after it was approved for certain individuals later during the trial? I was confused the first time reading this, since it was not clear why those in the SOC-only arm would be getting abiraterone. Authors should consider adding a clarifying statement or phrase at this part of the paper to remind readers that the SOC-only arm participants could have had AAP later during the course of their treatment (or if that is not the explanation, clarification on why they had AAP).

2. on page 11, in the paragraph just before Section 3.2, "and the goes on to describe" should be "and then goes on to describe"

Reviewer #2: The present article excels in approaching a drug whose clinical benefit has already been demonstrated in the literature (especially STAMPEDE, but also in other studies) but which has a high cost. The adoption of new health policies and the introduction of new medications must, in fact, take into account the economic component: public health is chronically lacking financial resources globally, and this pressure has been heightened in the context of the COVID-19 pandemic that we still meet.

Some doubts we observed during the study:

-It is reiterated several times throughout the article that the exact amount of abiraterone acetate paid by the UK healthcare system is not known.

-With the use of the algorithm developed, it was possible to reach a value, at least for patients in stage M0, in which its use would be economically viable, but as the real value paid is unknown, it is not possible to know if values similar to these are practiced.

-The study is largely based on the STAMPEDE study, taking into account projections stipulated by it, so it is at the mercy of its limitations and its own biases.

-Does not explain why the ICER (incremental cost-effectiveness ratio) was higher for subgroup M1 than M0.

The breach of the medication patent and studies that make the applied dose more flexible are among the changes in the scenario that can make the economic aspect more favorable to the wide adoption of the use of abiraterone acetate in the public health system.

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Reviewer #1: No

Reviewer #2: No

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Cost-utility analysis of adding abiraterone acetate plus prednisone/prednisolone to long-term hormone therapy in newly diagnosed advanced prostate cancer in England: lifetime decision model based on STAMPEDE trial data

PONE-D-22-01674R1

Dear Dr. Clarke,

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Kind regards,

Giandomenico Roviello

Academic Editor

PLOS ONE

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