A Q&A with Mark Shapiro, PhD,Vice President of Clinical Development at xCures, Inc., Partner at Pharma Initiatives; firstname.lastname@example.org. This is the final installment in a three-part series in which Dr. Shapiro has shared his thoughts on the question below. Read part 1 and part 2.
Q: Treatment of Americans with advanced cancer is complex and challenging and can be very expensive. Many urge greater participation of such patients in clinical trials. In general, who pays the expenses of clinical trials? And, specifically, how are the costs for Right to Try and expanded-access approaches reimbursed?
A: In clinical research, agreements between the research sponsor and the treating institution define what aspects of a study protocol are charged as research or related administrative costs, and what items are considered standard-of-care; that is, eligible for billing to insurance. This is made by a coverage review at the institution. While the sponsors provide the study drug freely to the site and patients, they expect to receive valuable data in exchange. In expanded access, which is treatment rather than research—but stills follows a protocol approved by the U.S. Food and Drug Administration (FDA)— sponsors pay the required administrative costs and the free provision of the investigational drug. The drugs are expensive, and the sponsor incurs additional compliance costs when they make an investigational drug available. So, expanded access is largely a charitable act on behalf of the sponsor. While there are regulations allowing sponsors to recoup their costs under expanded access, these are rarely used. Most sponsors, especially larger companies, deliberately plan for expanded access when planning manufacturing campaigns during oncology drug development. In fact, large sponsors report that they approve about 95% of the expanded-access requests that they receive.
Recently, the FDA commissioned a study by McKinsey & Company on their processes for expanded access and has been busy implementing several recommendations to streamline the administrative barriers. In that report, it was estimated that it takes a physician and their support staff an average of 30 hours to prepare a single-patient expanded-access request, so the FDA introduced a plan to prepare the requisite forms for single-patient expanded-access requests for doctors who request it. The cost of expanded access then is partly borne by the patient’s doctor, who must invest significant extra time to request the drug and comply with the additional responsibilities associated with using it.
These programs are for the primary purpose of treatment, not research. Nonetheless, ethicists have made it clear that there is an ethical imperative to learn from treatment provided under expanded access. Therefore, at xCures we try to learn as much as we can in the least burdensome way possible while helping to meet regulatory requirements for reporting on safety and patient outcome by using real-world data to further reduce the administrative burden for sponsors and physicians participating in expanded-access programs.
Under the Right to Try Act, the patient does not have a “right to try,” but they do have a “right to ask.” Specifically, they can ask their doctor, who, if suitably licensed to practice medicine, can ask a sponsor to make an experimental drug available. That is no different than expanded access—there is a right to ask. In both cases, the sponsor is under no obligation to provide the drug. The difference is that with Right to Try, a health insurer is not required to pay for care associated with the treatment, which contrasts with the coverage determination for clinical trials, including expanded access, conducted under an Investigational New Drug authorization.
The law does provide clarification about liability, which is another aspect of medical costs. The physician, their institution, and manufacturer are explicitly shielded from liability related to a drug administered under Right to Try for anything other than reckless or willful misconduct, gross negligence, or an intentional tort. I think this may reduce barriers to access, but in my experience, expanded access is not typically inhibited by insurance coverage, and only rarely does language around indemnification in compassionate use agreements become a contentious point of negotiation between sponsors and hospitals. In clinical trials, the consent must disclose who is responsible for costs in the event of a trial-related injury. Often that risk is insurable since adverse experiences that occur during a clinical trial are treated and billed normally. Under Right to Try, the costs of treating any adverse drug effects are likely to be billed entirely to the patient.
So, under Right to Try, the patient will bear the costs of medical care, and unlike an insurer with market power to negotiate discounted rates, they will likely pay the chargemaster rates. They may end up paying for the cost of the drug as well, since the Right to Try Act waives the application of sections in 505 and 351 prohibiting commercialization of unapproved drugs. Only those who are wealthy enough to completely self-pay their healthcare could reasonably access treatments under Right to Try, which could easily run into the hundreds of thousands of dollars (perhaps more). With expanded access, the cost is spread across the sponsor, insurer, institution, and patient, making it more accessible for now.
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