How the combination treatment challenge impacts patients and how we are working together to solve it

How the combination treatment challenge impacts patients

by Eric Low

Access to medicines attracts a great deal of interest from patients, clinicians, and the public and there have been significant advances in drug development in recent years which looks set to continue.

Many new treatments can provide improved outcomes for patients, extending and increasing their quality of life. However, in some cases, funding new treatments can present a challenge to health systems around the world as budgets are finite.  Therefore extensive consideration of the clinical and cost-effectiveness of treatments must be made, to justify their value for money and their value to the health system.

The combination treatment issue

Combination treatments combine two or more individual treatments, and have the potential to deliver significant clinical benefits to people with complex diseases such as cancer, HIV, rheumatoid arthritis, and Hepatitis C.

As understanding of disease increases, combination treatments are becoming increasingly common and critical to improving patient outcomes.

Combination treatments are often expensive, especially when multiple on-patent treatments are combined, which makes funding them a challenge for health systems. Often treatments included within a combination are developed by different companies and are priced independently. This poses a challenge as discussions between companies to agree on pricing and reimbursement are prohibited by strict competition law.

Increasingly, Health Technology Assessment (HTA) is used to determine which treatments health systems should fund and at what price. A fundamental requirement is that treatments must be seen to represent value. A treatment will therefore usually be priced at a level which the health system is willing to pay, based on its value.

Combination treatments are usually developed by either combining two or more existing treatments, or adding a new treatment to an existing backbone treatment or treatment combination.

As the use of combination treatments can potentially extend the lives of patients, the combination, including the backbone treatment, is used for longer.


This alone can increase the cost of the combination treatment above the willingness to pay threshold, even before the cost of the new add-on treatment is considered. Consequently, the combination treatment would be deemed  ‘not cost effective’, even if the add-on treatment was provided for free. This is problematic because combination treatments can provide value to patients and society but are unlikely to be made available to patients because they are not considered to offer value for money.

Impact on patients

A diagnosis of any rare or complex disease is likely to have an impact on both the quality and length of life of patients. For most, diagnosis or a relapse of disease will feel like a hard kick in the stomach and will be a terrifying confrontation with mortality.

Finding out that tolerable and effective treatments exist is an important step in helping patients come to terms with their diagnosis or a relapse. However, knowing that treatments exist but are not accessible due to cost-effectiveness issues is likely to cause emotional turmoil.

This is not a new issue; but it is one of many access to medicines issues that for too long has been seen as too hard to fix. With the steadily increasing number of potentially transformative combination treatments coming to market, it can no longer stay in the ‘too hard to fix box’.

Let’s also not forget that patients have taken part in drug trials to determine whether new combination treatments are better than the standard of care. Therefore, we have an ethical obligation to address any barriers standing in the way of future patients benefiting from their brave endeavours and involvement in clinical trials.

The importance of working together to solve this challenge

by Helen Taylor, Takeda

Sadly, one of the universal experiences of being human is that ourselves, families, and friends will be challenged during our lifetimes with ill-health and disease. So getting medicines to the right patient, at the right time, is critical.

Much of the HTA process is about gathering evidence from a multiplicity of different stakeholders to help make cost-effectiveness decisions about treatments. These decisions are not easily made by any of the stakeholders involved, so collaboration is key.

The 2014 report from the Decision Support Unit for NICE outlined the unique challenges and circumstances to assessing combination treatments and little progress had been made on a solution since.

At Takeda we recognised a need for change and in 2017, we held a parliamentary roundtable on this issue in conjunction with the Blood Cancer Alliance, to gain an understanding of the cost-effectiveness challenges for combination treatments from all angles. It was noted that access to combination treatments were either delayed, restricted or did not happen at all. There was strong consensus that there was a pressing need for a solution to be found.

In the years that followed, numerous stakeholders started to review the issue and propose approaches to address the challenge. In 2018, the Amyloidosis Research Group Consortium UK raised the concept of voluntary arbitration between pharmaceutical manufacturers.

In 2019, the Bellberry Group convened an international group of HTA experts to discuss the challenge and, also in 2019, the Voluntary Scheme for Pricing and Access (VPAS) UK acknowledged the challenge and suggested that industry take a lead role in the development of any potential solutions.

In the same year, Takeda UK established an Advisory Group of experts from academia, clinical and patient communities to clearly identify all the issues and design a transactable and implementable solution. We sought expert input from NICE and the NHS on key challenges and to align the solution with current NICE appraisal and NHS England commercial methods.

Takeda’s proposed solution, detailed in two Whitepapers (An Attribution of Value Framework and the Voluntary Arbitration Framework), aims to address the economic and competition law hurdles Eric highlighted.

The economic methodology describes how you can fairly divide the value across the treatments within a combination, while the standard operating procedure supports compliant dialogue and agreement between pharmaceutical companies on the value attributed to each treatment within a combination.  The solution is treatment and disease agnostic and, although it utilises NICE’s methods and processes, we believe it can be adapted for multiple countries and market archetypes.

Next steps and call to action

Both myself and Eric Low have been working on this solution with a core team of passionate and dedicated individuals for the last few years and are delighted to be able to share it. Our proposed solution aims to contribute to the tapestry of options being explored by other stakeholders.

We now invite colleagues and senior leaders across the industry and wider healthcare community to consider the challenge, to review, critique and debate both Whitepapers, so we can ultimately work together to develop an actionable universally agreed solution.

The VPAS asked industry to take a lead role in developing potential solutions, and we hope that our collective brain power can deliver. Keeping patients at the centre of our focus is pivotal to our industry’s raison d’être.

To download the Whitepapers, please see this link.

Thoughts and feedback can be directed by email to the Takeda team at

About the authors

Eric Low

Eric Low currently runs a consultancy business specialising primarily in strategic market access, life sciences and healthcare policy, patient, and patient group engagement. He has worked in the fields of medical research, market access and patient organisations for over 25 years and set up Myeloma UK in 1996, leading the organisation as Chief Executive until 2017. Eric holds several Board, honorary, advisory, and voluntary positions. He also advises numerous medical and health-focused charities on a pro bono basis. He was awarded an OBE for services to charity in the Queen’s Birthday Honours 2012.

Helen Taylor

Helen Taylor is programme realisation manager at Takeda where, for the last three years, she is responsible for supporting the director of Market Access and head of Appraisals & Centre of Excellence involving optimal planning, early scientific advice projects and risk management. Helen has also provided consultancy guidance for over 13 years in various roles and finally as a Research Associate Partner at MMRG Ltd, a company of healthcare innovation specialists.

Date of prep: October 2021

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