Drugmakers and physician groups expressed concern about connecting patient reported outcomes (PRO) to coverage decisions for chimeric antigen receptor T-cell therapy (CAR T) at a recent Medicare meeting.
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Despite these objections, members of the Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) generally expressed confidence in the use of PROs in a series of votes about PRO instruments’ use in cancer care trials.
MEDCAC opened a national coverage analysis in May 2018 at the request of UnitedHealthcare. The insurer had asked the Centers for Medicare & Medicaid Services to clarify the circumstances for coverage of the new CAR T therapies.
In presentations at an Aug. 22 MEDCAC meeting, representatives from the two manufacturers that have approved CAR T treatments on the market cautioned against using PROs in the context of coverage decisions, even though both companies used PRO data in their clinical trials and are collecting it in the postmarketing period.
“While Kite recognizes the importance of PROs in ... clinical trials, the PRO CAR T science, where these instruments are most appropriate for CAR T, remains a still to be determined and still is evolving and still quite early in the developments,” said William Go, MD, PhD, vice president of clinical development at Kite Pharmaceuticals, a Gilead company.
Despite PROs playing an active role in the ongoing development and clinical trials that Kite is running, in the context of CAR T, “we feel PROs are not quite ready for real-world coverage decisions at this time,” Dr. Go said.
A representative from Novartis agreed. “It is important to clearly define research objectives when considering whether to collect patient reported outcomes data, particularly given the burden associated with advanced disease experienced by the patients that are likely to receive this therapy,” Ilia Ferrusi, PhD, associate director, HEOR (CAR T Therapy), U.S. Oncology, Novartis, told the panel.
She noted that Novartis experienced challenges collecting PRO data, which resulted in risks to data quality and interpretation. “This could very well be amplified in larger trials or in real-world practice.”
The presenters’ comments were echoed by written comments submitted to the CMS prior to the MEDCAC meeting.
The American Society for Blood and Marrow Transplantation (ASBMT), despite supporting the collection of patient-reported outcomes, particularly in oncology, “strongly objects to any mechanism that would tie patient access or provider reimbursement to the reporting of PROs, especially in the case of CAR T therapy,” the organization said in a letter to the CMS.
Optimal PRO instruments and time points “are currently unknown” as the PROs used today were developed around chemotherapy use.
“Mandating the use of a current instrument or set of outcomes through NCD [national coverage determination] or CED [coverage with evidence development] will set a course of collecting data that is very likely to be inaccurate and inadequate,” they said.
The ASBMT also noted there is significant heterogeneity in the CAR T constructs and associated disease indications. “Products will utilize different scientific constructs and the time frames for clinical response and/or potential onset of toxicities may differ for each construct, which will challenge the establishment of set time points for data collection.”
And while presentations and comments focused on PROs in the context of CAR T, conversation and voting on the use of PROs was in the broader context of oncology clinical trials, not specific to CAR T, changing the nature of the debate and calling into question the point of the meeting and how it will inform the national coverage determination on CAR T specifically.
The June 15 meeting announcement published in the Federal Register stated that the advisory committee “will specifically focus on appraisal of evidence-based PRO assessments to provide information that impacts patients, their providers, and caregivers after a CAR T-cell therapy intervention for the patient’s cancer.”
However, the committee was asked to evaluate evidence on a number of potential PRO instruments in the broader context of oncology clinical trials without a cancer-specific or treatment-specific context, leading to a debate over how different types of cancer will have different kinds of PRO assessments related to them.
The CMS is expected to make a national coverage decision on CAR T-cell therapy by Feb. 16, 2019.