Consensus lacking on ‘value’ for new anticancer drugs

Regulatory NewsRegulatory News | 08 December 2021 |  By 

The high price tag of new anticancer drugs has fueled debate about the value of these treatments, given the marginal clinical benefit of some newly approved treatments. But that debate is complicated by a lack of consensus around the definition of value and the different views of stakeholders in cancer care.
In a recent perspectives article in Nature Reviews, authors from the European Medicines Agency (EMA) and the Karolinska Institutet in Sweden explored the different approaches for determining an anticancer drug’s value among regulators, payers, patients, and clinicians. They also outlined the benefit-risk assessments used in drug approval decisions by the EMA and the US Food and Drug Administration (FDA).
“Rather than attempting to reconcile conflicting definitions and objectives, understanding all the different perspectives is important to ensure that they do not lead to marked inefficiencies, such as multiplication of trials and requirements that would lengthen and stifle the clinical development of promising new drugs,” Francesco Pignatti, of the Oncology and Hematology Office at the European Medicines Agency, wrote in Nature Reviews. The opinions expressed by the authors do not necessarily reflect the policies of their institutions.
The authors urged transparency about the objectives and values of each stakeholder to help in making judgements about the value of anticancer treatments.
Differing perspectives
Regulators typically assess benefits first and, if a clinically significant benefit exists, they evaluate whether the toxicity profiles appear to be acceptable for the patient, the authors explained. These judgements are typically made from a patient-centered approach, rather than a societal perspective. This approach has resulted in the approval of some drugs with “marginal therapeutic value.”
“These approvals have been criticized for cluttering the market with expensive interventions, fostering misinformation, raising false hopes, putting unnecessary strains on health-care budgets, providing disincentives to innovation, slowing drug development by depleting precious resources and preventing patients from enrolling in clinical trials of interventions that might be perceived as more valuable,” Pignatti and colleagues wrote.
Regulators in both the EU and the US do not consider cost when evaluating whether to approve new drugs. Payers, on the other hand, take a different approach. In the EU, evaluations of relative effectiveness or cost effectiveness are carried out by member states’ health technology assessment (HTA) agencies and pricing bodies. The United Kingdom’s National Institute for Health and Care Excellence (NICE), for instance, uses cost per quality adjusted life year (QALY) to evaluate new drugs. Several anticancer drugs have fallen short of the predefined cost-per-QALY threshold, drawing criticism from clinicians and patients.
From the clinician perspective, groups like the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) have developed scales aimed at rating the clinical benefit of new anticancer drugs, with the aim of weeding out drugs without meaningful clinical benefit. But these scales have drawbacks that limit their potential use by regulators, the authors noted. For instance, ESMO’s scale relies on evidence from pivotal clinical trials rather than data from clinical practice and post-approval studies. The ratings are also based on expert views rather than patient-report outcomes. Additionally, clinician scales typically measure the benefits added by individual treatments relative to existing drugs, rather than looking at benefits compared with placebo.
Patients approach the debate with a different perspective since even treatments that offer low clinical benefits overall may have a small group of responders who benefit greatly. For instance, with the metastatic melanoma drug ipilimumab, only about 20% of patients have durable responses but survival data suggests that the drug can be a cure for some percentage of those patients. However, unless researchers can prospectively identify which patients will respond to a drug, “Determining the preferred treatment will be a matter of individual circumstances and risk attitudes, even when the probability of benefits is low relative to the likelihood of harms,” the authors wrote.
Transparency key for regulators
While the various cancer care stakeholders come to the debate with different perspectives, there is an opportunity for regulators to help everyone, the authors wrote, by communicating complete information on all relevant drug outcomes.
EU regulators currently use a standardized format to report outcomes from pivotal clinical trials and a structured approach for communicating benefits and harms. Additionally, the EMA has established a policy of publishing documentation about clinical trials submitted by applicant companies.
The authors also suggested that regulators and HTA bodies could work together to define the evidence that should be collected before and after a drug approval, such as post-approval data from disease registries or data sharing initiatives, or even studies to identify biomarkers that would aid in patient selection.
The value of anticancer drugs – a regulatory view


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