Clearer Definitions of Added Benefit, Unmet Needs Could Improve EU Oncologic Drug Approval Process


Investigators emphasize the importance of firming a widely understood definition of unmet needs in cancer care due to their impact on drug approvals.

Francine Brinkhuis, MSc

Francine Brinkhuis, MSc

Francine Brinkhuis, MSc, a PhD candidate in the Division of Pharmacoepidemiology and Clinical Pharmacology of the Utrecht Institute for Pharmaceutical Sciences at Utrecht University in the Netherlands, and Lourens T. Bloem, PharmD, MSc, an assistant professor of Clinical Therapeutics at the Centre for Clinical Therapeutics of the Division of Pharmacoepidemiology and Clinical Pharmacology, at the Utrecht Institute for Pharmaceutical Sciences, discussed their investigation into the association between added benefit and the revenues of oncology drugs approved by the European Medicines Agency in an interview with OncLive®. The study co-authors provided insights into the findings of their research published in The BMJ.

The investigators also explained how unmet needs in cancer care factored into this research, highlighting the need for a better definition of the term, as unmet needs in oncology factor into the regulatory approval of these agents. Previously, Brinkhuis and Bloem shared further insight into the background of their research.

OncLive: You investigated the added benefits and revenues that are recouped for approved oncology drugs within the European Union (EU). What are the implications of these findings?

Brinkhuis: There are new implications [from these findings]. It would be important for physicians to realize that oncologic products that have been approved via expedited pathways are associated with greater uncertainties [regarding added benefit]. We do see that they are prescribed a lot because they generate their revenues quickly and their R&D costs are recovered within a few years.

Additionally, it's important that we show that at initial approval, even if there is a lack of proof of added benefit, revenues are high. It would be interesting to monitor [added benefit] over time because it could be possible that additional evidence will become available after a few years, which may or may not prove [a drug’s] added benefit. It's good to get insights into [added benefit] and make it transparent how much added benefit these products have, as well as how much revenue they generate.

The third thing is to promote the rational use of products. Oncology drugs are quite expensive, but a way to lower those costs may be to use these products in practice more efficiently. For example, we can look at dosing or administration strategies. There was a study in the Netherlands that found that if a certain product was used in a later line of treatment, the effects would be the same for patients, but the cost would be significantly lower.

Similar studies have looked at dosing strategy, hypothesizing that if you use lower doses, there may be lower toxicity, but the effects [of the treatment may be] the same and the costs are also lower. That's also something that may be valuable.

Bloem: The rational use [of oncology drugs] would require different studies, [such as real-world trials] and pragmatic trials. We should promote these studies more and more to be performed post-authorization, which could also address those gaps in evidence [of added benefit] that can be there at the moment of authorization.

If we are requiring those studies, then there should also be studies that provide more insight into the actual situation to use these drugs, whether it be dosing, patient population, or lines of treatment.

How do unmet needs factor into these approvals and their association with revenue?

Bloem: There is an ongoing discussion in Europe about the definition of unmet medical needs and how these needs are then used by different organizations, health care institutes, and health care organizations in their reasoning of approving or reimbursing medicines.

There is a lot of discrepancy regarding what is perceived, how unmet medical needs are measured, and how they can be used [to justify approvals]. A lot of work should be done to make sure that there is more common ground on when expedited pathways can be used and when [more] comprehensive evidence should be accessible. Evidence [of added benefit] might still become available, especially for the [drugs approved through] expedited pathways, meaning conditional marketing authorization predominantly for the EU and accelerated approval [by the FDA] in the United States.

There is an evidence dynamic that's still growing. Often, we already have a fixed price at the moment of initial authorization or around it. Regarding that dynamic of incoming evidence, we should make sure that there is a good system to respond to that evidence. One of the best options is to have a lower initial price in the circumstance of higher uncertainty [of added benefit], and then as soon as that uncertainty gets resolved and the added benefit can be shown, then we may as a society want to pay a higher price [for that particular drug]. Currently, we don't have a price dynamic. It's just a fixed price among these patient populations, [leading to] larger indications, higher prices, and higher revenues; that might not be the system that we want to stick to.

What would you like your colleagues to take away from this research?

Brinkhuis: [Added benefit should be] monitored over time. We made [our] ranking scale based on 4 levels of added benefit. The lowest level contains both no added benefit and non-quantifiable added benefit. It would be interesting to look in more detail at the group that's non-quantifiable to see what happens over time. Will it get quantifiable at some point? Will [the added benefit rating] then be positive or negative?

Maybe products that have been given a positive rating will [maintain] that over time and [demonstrate], in practice, that they do give added benefit to patients.

Bloem: The biggest insight from the whole study is that, despite lack of proof of added benefit, there is still lots of revenue, and even so much that costs are being recouped within a median of 3 years. That begs the question of what we as a society want to pay for these medicines when we don't have full insights into added benefits.

We have these uncertainties, raising the question [around] what circumstances we fully agree that the system is good as is. Maybe in specific indications, we can say that we already have quite [a few] treatments, and we don't want this [new one] now [without proof of added benefit]; maybe we need more firm, better evidence on added benefit.

Additionally, if you zoom out a bit more away from cancer medicines, you can also say that as a society, we're paying so much [money] within the cancer arena; however, aren't there other diseases that we should be paying for to ensure that there are more innovations? That's a large question, of course, but it is relevant to take that perspective and have a societally broad discussion.


Brinkhuis F, Goettsch WG, Mantel-Teeuwisse AK, Bloem LT. Added benefit and revenues of oncology drugs approved by the European Medicines Agency between 1995 and 2020: retrospective cohort study. BMJ. 2024;384(e077391). doi:10.1136/ bmj-2023-077391

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