oncology combination pricing

What is a fair value for oncology combination pricing?



The use of combination pricing is fast becoming the standard of care in oncology treatments, with 300 active clinical trials currently exploring the possibilities of different treatment combinations for cancer1. Although the multi-prong treatment approach seems to be growing in popularity, there remain a number of challenges to be addressed, specifically regarding budget impact and issues with cost-effectiveness that payers struggle to reconcile. The dichotomy between the efficacy of combination treatments and the challenges regarding value and cost effectiveness raises the question: what is a fair value for oncology combination pricing? This article will discuss the value of combination pricing as seen by HTA agencies, and how challenges can be addressed by payers and manufacturers to enable patients to benefit from these therapies.

What are the challenges surrounding combination pricing?

Novel on-patent drugs historically were combined with relatively inexpensive generics, however it has become more commonplace to combine a novel drug with an existing branded on-patent drug. The combination of these two branded drugs often results in the cost of the combination being above the threshold payers find acceptable for the treatment. Due to the lack of cost-effectiveness, appraisal for the combination often results in a lack of reimbursement, presenting a significant challenge for manufacturers of oncology combination therapies. An assessment into reimbursement decisions for combination and monotherapies for lung cancer and multiple myeloma in France, Germany, Italy, Spain, and the United Kingdom showed a 35.7% rejection rate for combination therapies compared to 11.4% for monotherapies between 2011 and 2020, highlighting difficulties in gaining reimbursement2. Situations in which this problem arises were explored by attendees at the Bellberry Group international workshop, a 2-day workshop attended by stakeholders around the world with the goal of discussing affordability and value for money challenges, specifically regarding combination therapies. Hypothetically, both drugs in the combination may have been priced individually, or one drug may have been designed as an add-on for the backbone therapy3. Although the combination may have increased efficacy, the doubling of price may not necessarily mean the doubling of value, and payers therefore may not see this as good value for money. If the add-on therapy results in an increase in months lived, the backbone therapy is used for longer than initially intended, increasing costs in an economic model and making it difficult for the add-on to be cost-effective.

This scenario can result in some clinically effective combination therapies not being cost-effective even if the price for the new add-on treatment is 0. This situation occurred with the first appraisal of the drug pertuzumab in combination with trastuzumab and docetaxel when appraised for their use in breast cancer4. Although pertuzumab as an add-on resulted in progression-free survival gains of 6 months over the original backbone treatment, it was still not found to be cost-effective at a price of £0. This was due to the prolonged usage of the trastuzumab/doctaxel backbone therapy.

Another challenge facing combination pricing is the penalisation of companies unable to demonstrate sufficient added clinical benefit. The recently passed financial stabilisation act in Germany has resulted in the G-BA enacting a 20% rebate on for brand-brand combination drugs5, excluding only those that receive a major or considerable added clinical benefit rating. This affects both backbone and add-on therapies, becoming another obstacle for manufacturers to overcome to obtain access to their combination therapy. Thus far, negotiations for acceptable pricing between manufacturers and payers and the search for a fair value for oncology combination therapies has been unfruitful. What have HTA agencies done to search for a solution?

What have HTA bodies done to address these challenges?

Due to the complexity behind finding a cost-effective balance for combination pricing for both payers and manufacturers, no significant solutions to this problem have been identified. There are however ongoing discussions and international recognition of this problem, with multiple stakeholders representing HTA agencies, academia, pharmaceuticals, and the patient industry attending the Bellberry Group international workshop. NICE have also highlighted their involvement in ongoing work to identify solutions to these issues, specifically where add-on therapies are not cost effective in combination with backbone therapy6. Moreover, the 2022 NICE health technology evaluations manual specifies that if a technology increases survival in people where it would not be considered cost-effective at NICE’s normal levels, they may consider a non-reference case analysis with background care costs removed7. The ABPI has also raised the issues surrounding access to combination therapy, and have announced that they will be supported by NHS England and NICE in engaging the UK Competitions and Markets Authority to produce guidance on a proposed approach for companies to engage with each other when combination therapies will not otherwise reach patients8.

The solutions proposed by experts involve a contribution from both manufacturers and HTA bodies. Firstly, HTA agencies may consider altering their decision-making frameworks for combination therapies. Thus far, the pricing and decision-making frameworks employed for determining the value for monotherapies are also used for combination therapies. A future update might consider introducing increased flexibility in the assessments of combination treatments, and possibly introducing combination therapies as a modifier in decision making/value assessment frameworks to permit a higher price3. Another possible solution could be to allow the realignment and discussion of individual component prices to allow for cost-effectiveness, an action that is currently prohibited under competition law if constituent therapies are owned by different companies9.

Recommendations for manufacturers

In addition to HTA bodies considering updates to their methods in assessing combination therapies, companies may want to consider specific actions to address the problem of value in oncology combination therapy to maximise potential value. Pharmaceutical companies may want to collaborate with healthcare and HTA bodies in the development of new frameworks for access to combination therapies that highlight the need to allow new medicines to vary in price dependent on usage1. Moreover, manufacturers may want to engage in cross-company dialogue in a way that does not infringe competition law to allow the determination of a price that can be proposed to NICE that may address the problems of cost-effectiveness8. As this is not just an issue for manufacturers, both HTA bodies and manufacturers should engage in actions that help determine a fair value for oncology combination therapies, so patients do not lack access to potentially life-saving therapies.


To conclude, what is a fair value for oncology combination pricing? The truth is that this is a complex question that does not yet have a definitive answer. Different countries may have different parameters in assessment, such as cost-effectiveness and added clinical benefit but the issue remains the same, that with current methodology, combination pricing often is not seen as a good value for money. To reach a conclusion on what a fair value for combination oncology pricing is, significant input and collaboration between HTA agencies, healthcare bodies and pharmaceutical companies is needed.

View additional resources on combination pricing and oncology:

Market Access combination pricing impact – Remap Consulting

High-cost oncology combination therapies – Remap Consulting


1.         Combination treatments in oncology. Sanofi. Accessed 1st June 2023.

2.         Izmirlieva, M.A., Reinaud, F., Taiyeb, M., Ando, G. 2022. P29 Reimbursement Outcomes for Combination Therapies vs Monotherapies in Lung Cancer and Multiple Myeloma in the Top Five European Markets. Value in Health. 25(1). DOI:

3.         Latimer, N.R., Pollard, D., Towse, A. et al. 2021. Challenges in valuing and paying for combination regimens in oncology: reporting the perspectives of a multi‐stakeholder, international workshop. BMC Health Services Research. 21. DOI:

4.         Pertuzumab with trastuzumab and docetaxel for treating HER2-positive breast cancer. NICE. Accessed 1st June 2023.

5.         The German Financial Stabilization of Statutory Health Insurance System Act. Trinity Life Sciences. Accessed 1st June 2023.

6.         Decision making task and finish group report. NICE. Accessed 1st June 2023.

7.         NICE health technology evaluations: the manual. NICE. Accessed 1st June 2023.

8.         Patient access to combination therapies. ABPI. Accessed 1st June 2023.

9.         Paving the way for reimbursement of cancer combination therapies. Newmarket Strategy. Accessed 1st June 2023.

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