How the First International Summit on Interventional Pharmacoeconomics Is Sparking Discussion on Reducing Cancer Costs

A Conversation With Mark J. Ratain, MD

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Mark J. Ratain, MD

Mark J. Ratain, MD

Three years ago, former Chief Executive Officer of ASCO, Allen S. Lichter, MD, Laurence H. Baker, DO, Professor in the Departments of Internal Medicine and Pharmacology at the University of Michigan Medical School in Ann Arbor; Leonard Saltz, MD, a gastrointestinal oncologist at Memorial Sloan Kettering Cancer Center; Jonas de Souza, MD, MBA, Medical Director of Humana; and Mark J. Ratain, MD, Leon O. Jacobson Professor of Medicine, Director of the Center for Personalized Therapeutics, and Associate Director for Clinical Sciences at the Comprehensive Cancer Center at the University of Chicago Medicine, met at the ASCO Annual Meeting to discuss their newly formed organization: Value in Cancer Care Consortium (

Its mission is to lower the costs of many oncology drugs through the application of alternative dosing strategies or substitution of a lower-priced agent. The organization also aims to demonstrate that these actions maintain treatment effectiveness and patient benefit—a new strategy the group has labeled interventional pharmacoeconomics.

As proof of concept, the viability of reducing a drug dose while maintaining its efficacy was demonstrated with a phase II randomized study by Szmulewitz et al, evaluating the food effect on the pharmacokinetics and pharmacodynamics of abiraterone in men with castration-resistant prostate cancer.1 In the study, 72 patients were randomly assigned to receive either the standard dose of 1,000 mg/d of abiraterone while fasting as directed on the label or 250 mg/d and taking the drug after eating a low-fat breakfast. The study found that in addition to meeting the primary endpoint of noninferiority of prostate-specific antigen (PSA) change, there was also evidence of equivalent targeting of CYP17 inhibition and PSA progression-free survival. The study also showed how reducing the dosage of the then $9,400-a-month drug could potentially slash its cost to patients and payers by 75%.

The success of this study, as well as other studies showing the cost and side-effect benefit of this strategy along with comparable outcomes,2 led members of the Consortium to organize the First International Summit on Interventional Pharmacoeconomics, which was presented virtually early this summer.

About 100 attendees from the United States, Israel, Canada, Europe, Asia, and South America attended the 3-day meeting, which included a keynote address by Clifford A. Hudis, MD, FACP, FASCO, Chief Executive Officer of ASCO, called “Are Cancer Drug Prices in the United States the Problem or the Symptom?” as well as presentations by Cody J. Peer, PhD, staff scientist at the National Cancer Institute; Dr. Saltz; and S. Vincent Rajkumar, MD, Professor of Medicine at the Mayo Clinic in Rochester, Minnesota. (See page 68 for a conversation with Dr. Rajkumar on “How to Treat Patients With Multiple Myeloma Cost-Effectively Without Compromising Outcome.”)

The ASCO Post talked with Dr. Ratain about the challenges of conducting interventional pharmacoeconomic oncology studies; the importance of matching the price of a drug with its clinical value; and what it will take to reduce the costs of oncology care.

Overcoming the Barriers to Reducing Drug Costs

What were the major takeaways from this online summit?

For me, the major takeaway was that there is definitely a community of people who are interested in solving the problem of the escalating costs of oncology drugs, as well as getting the issue of dosing right. That was encouraging to us.

What are the challenges of conducting interventional pharmacoeconomic oncology studies?

I would say the biggest barrier is finding interest in designing trials that are not just focused on advancing survival, response rate, and cure of patients with cancer. The second biggest barrier in the United States is that, historically, oncologists’ income is correlated with the amount and cost of the drugs they prescribe. It is changing a bit now, as we move into new model of care for payment and delivery, but we do not have the incentives right. For example, in one presentation, Blase N. Polite, MD, MPP, FASCO, Professor of Medicine and Hematology/Oncology and Executive Medical Director for Cancer Accountable Care at the University of Chicago Medicine, suggested we should have oncology cost pathways and incentivize physicians to follow the most cost-effective pathway.

“We believe many drugs could safely and effectively be given at lower doses, less frequently, or for shorter durations.”
— Mark J. Ratain, MD

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For instance, let’s say there is a biosimilar available for a newly approved oncology drug and it costs 25% less than the new drug. Physicians should be financially incentivized to prescribe the most cost-effective drug, which generally would be the biosimilar. We do not have those incentives, however, so the newer, more expensive drug is often prescribed.

Funding to do interventional pharmacoeconomic studies is also challenging. The National Health Service in the United Kingdom definitely sees funding these types of studies as an opportunity to reduce the cost of drugs and find the best treatment regimens through lower doses, less-frequent dosing, and shorter duration of dosing, as well as therapeutic substitutions. However, such funding is unlikely to come from the Centers for Medicare & Medicaid Services for the National Institutes of Health to conduct trials to reduce health-care costs for Medicare and Medicaid beneficiaries. There are many opportunities for these types of studies, but it takes a will to fund and implement them. These ideas seem to resonate well outside the United States, particularly in countries with single-payer health-care systems or where there are huge incentives for patients to reduce their health-care costs (eg, Singapore and low- and middle-income countries such as India.)

Launching Interventional Pharmacoeconomic Studies

What level of research evidence is needed to justify giving a drug at a lower dose or less frequently than the dosing tested by the manufacturer and approved by the U.S. Food and Drug Administration (FDA)?

I would be comfortable with the same level of evidence we generated in the abiraterone study. Many physicians, however, are uncomfortable with the notion of prescribing less drug, and some physicians will never prescribe anything off-label unless the drug manufacturer is supportive. We were lucky that the National Comprehensive Cancer Network® changed its Guidelines for prostate cancer to include the lower dose of abiraterone. It now states: “Abiraterone with prednisone can be administrated at a dose of 250 mg/day following a low-fat breakfast, as an alternative to the dose of 1,000 mg/day after an overnight fast. The cost savings from this doing may reduce financial toxicity and improve compliance.”3

When we get wins like this we celebrate, because we know this is a David vs Goliath battle.

Matching the Price of a Drug to Its Clinical Value

Historically, you mentioned, oncology drugs have been developed using the paradigm that more is better. How might you prove that paradigm is wrong?

The Value in Cancer Care Consortium is proving the paradigm is wrong, which is based on belief rather than science. In the past, there has been no penalty for getting a drug approved at a dose that is too high. We are injecting some checks and balances into the system that no one else has been willing to provide. I am hoping that in 10 years, there may be no new opportunity to lower the cost of drugs because they will all be labeled at the right dose and frequency.


To see an interview with Mark J. Ratain, MD, on making a case for low-dose ibrutinib in chronic lymphocytic leukemia, visit The ASCO Post Newsreels at

We now believe there is compelling evidence that the Bruton’s tyrosine kinase inhibitor ibrutinib in the treatment of chronic lymphocytic leukemia reaches its maximum clinical effect at doses well below the labeled dose of 420 mg and that the drug is unsafe for many patients at that higher dose. A small pilot study by Chen et al has demonstrated that reducing the dose of ibrutinib from 420 mg to 140 mg maintained the drug’s efficacy while reducing inhibition of platelet function, a marker of bleeding risk.4 And, because the drug is formulated as 140-mg capsules, it is likely the cost of the drug could be reduced by two-thirds.

Our question is, why doesn’t the FDA mandate a study of ibrutinib at the lower dose? The message we are trying to get across is these types of studies need to be done, whether they are mandated by the FDA, voluntarily conducted by pharma, or initiated by academic investigators. We believe many drugs could safely and effectively be given at lower doses, less frequently, or for shorter durations.

Getting Buy-in From All Stakeholders

What is your message to ASCO members about these pharmacoeconomic issues?

The continuing escalation of drug costs cannot be sustained, and it is everyone’s problem to solve, including payers, employers, government, and health-care professionals. In the absence of complete regulation of drug prices, the best alternative is the development of innovative dosing regimens that maintain equivalent efficacy and safety while deriving maximal value.

The result in savings to the health-care system could be in the tens of billions of dollars each year. Although there are obstacles to overcome in making interventional pharmacoeconomic studies a reality, we should not miss this opportunity to provide a mechanism for not only reducing drug costs, but to provide patients with equal or greater clinical value as well. 

DISCLOSURE: Dr. Ratain has served as a consultant or advisor to Apotex, Aptevo Therapeutics, Cyclacel, Genentech, and Pneuma Respiratory; has received institutional research funding from AbbVie, Boston Biomedical, Bristol Myers Squibb, Corvus Pharmaceuticals, Genentech/Roche, Incyte, and Xencor; holds intellectual property related to UGT1A1 genotyping for irinotecan and to a genomic prescribing system; holds institutional intellectual property related to UGT1A1 genotyping for irinotecan to a genomic prescribing system; has provided expert testimony on behalf of “multiple generic companies”; and has other financial relationships with BeiGene and Value in Cancer Care Consortium.


1. Szmulewitz RZ, Ibraheem AF, Peer CJ, et al: A prospective international randomized phase II study evaluating the food effect on the pharmacokinetics and pharmacodynamics of abiraterone acetate in men with castration-resistant prostate cancer. 2017 Genitourinary Cancers Symposium. Abstract 176.

2. Ratain MJ, Goldstein DA, Lichter AS: Interventional pharmacoeconomics: A new discipline for a cost-constrained environment. JAMA Oncol. June 20, 2019 (early release online).

3. Schaeffer E, Srinivas S, Antonarakis ES, et al: NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer, version 2.2020–May 21, 2020. Available at Accessed August 7, 2020.

4. Chen LS, Bose P, Cruz ND, et al: A pilot study of lower doses of ibrutinib in patients with chronic lymphocytic leukemia. Blood 132:2249-2259, 2018.