Reimbursement decision making and Innovation in Oncology

Cancer is a leading cause of death worldwide, and it’ll affect 1 in 2 men, and 1 in 3 women during their lifespan. By 2022 it affected 19 million individuals.

The therapeutic and diagnostic innovations have led to significant improvements in survival for most of the cancer patients, but this doesn’t come at no cost. Many of these therapies besides eliminating cancerous cells, also cause damage to healthy ones, leading to what is known as adverse events (AEs). These AEs have negative impact not only on the quality of life (QoL) of affected patients, but also poses significant economic burden on the health systems (1). Management of AEs have not only impact on the healthcare resources but it can also have indirect medical costs such as loss of productivity, caretaker time etc.

During the drug approval and at the time of marketing, the quality of life and side effects are evaluated, yet the amount of information on benefits and risks, especially long term, are relatively small. The premarketing studies of new drugs cannot always reliably detect rare but potentially important AEs due to a variety of reasons, as nicely summarized in this publication (2). As discussed by authors of this paper, clinical trial participants often represent a healthier subset of patients, they may receive better care and evaluated drugs will be given for shorter duration in studies than in postmarketing use, which altogether may represent somewhat different situation from the one observed in real-life setting.

This is by no means, a criticism of clinical trial execution – launching innovative therapies should be done effectively, and the community is focused on enabling its access and benefits to as many cancer patients as possible, but this should also be carefully balanced against its potential harms.

Cancer drug reimbursement traditionally is based on assessment of overall survival (OS), where the goal is to show that patients treated with the experimental drug live longer compared to a control groups. However, as the treatments are becoming more effective and thereby patients are thankfully living longer, as well as some cancer indications are known as slow progressing, OS becomes a questionable endpoint. With that in mind, the community has been assessing alternative endpoints like time to disease progression, progression free survival (PFS) and pathologic response which offer earlier insights into the effectiveness of evaluated therapeutics. However, some of these endpoints such as PFS do not come without question marks, as I’ve discussed it in my ESMO takeaway article. How should be evaluated the drugs that improve PFS but not OS? And what about the AEs of a drug which may improve PFS but leads to poorer QoL?

As we’ve heard it by many patient advocates, the QoL is one very important metric which should be used for evaluation of novel therapies. Along those same lines, there is a growing emphasis on Patient Reported outcomes (PROs) and that they should be considered for drug approval processes rather than endpoints such as OS. But what are PROs? PROs are defined as the patient’s own accounts of their feelings, functioning, way of life, and ability to survive and can be used as a proxy for QoL. As recently discussed during an interesting European Federation of Pharmaceutical Industries and Associations (EFPIA) hosted webinar (3), there is still a lot of inconsistencies with regards to data collection and reporting of PROs, so there is a need to define and ultimately harmonize collection of PROs across different disease and stages. The successful implementation of these improvements could lead to the use of PROs as an alternative end-point within the drug approval process. Additionally, all of these aspects should also be considered by teams involved in evidence generating activities, since you would want to include the most relevant PROs in your pivotal studies.

Payers and health technological assessment (HTA) experts acknowledge OS limitations during the HTA of new therapies but are hesitant with regards to the benefits of alternative endpoints, fearing these could be somewhat subjective and could lead to added treatment burden and costs without clear improvements. To address this, there are ongoing conversations about generating evidence supporting the stand-alone value of other endpoints and allocating weight to outcomes other than mortality in HTA evaluations.As previously stated, we must promote innovation in the field of oncology, both in the diagnostic and treatments domains, while carefully weighing the advantages and disadvantages and remaining within the means of health care systems.

As previously stated, we must promote innovation in the field of oncology, both in the diagnostic and treatments domains, while carefully weighing patient benefits and harms, while remaining within the means of health care systems.


1.       San Jose-Saras D, Valencia-Martín JL, Vicente-Guijarro J, Moreno-Nunez P, Pardo-Hernández A, Aranaz-Andres JM. Adverse events: an expensive and avoidable hospital problem. Ann Med. 2022 Dec;54(1):3157-3168. doi: 10.1080/07853890.2022.2140450. PMID: 36369717; PMCID: PMC9665082.

2.       Berlin JA, Glasser SC, Ellenberg SS. Adverse event detection in drug development: recommendations and obligations beyond phase 3. Am J Public Health. 2008 Aug;98(8):1366-71. doi: 10.2105/AJPH.2007.124537. Epub 2008 Jun 12. PMID: 18556607; PMCID: PMC2446471.



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