Combination treatments are comprised of a ‘backbone’ treatment, often considered to be the existing standard of care, combined with a new ‘add-on’ treatment. Despite potentially delivering significant clinical benefits for patients with complex diseases, they often face cost-effectiveness barriers that result in a lack of patient access or reimbursement of these treatments. This article looks at this issue and a potential solution for the pharmaceutical industry and broader community to consider and work together to deliver.

In 2014, the Decision Support Unit (DSU) for the National Institute for Health and Care Excellence (NICE) published a report that outlined the circumstances in which medicines that are clinically effective, may be deemed not cost-effective even at zero price.

You may be wondering how this can be possible, how can something be free yet still not be cost-effective? There are several scenarios where this may happen, but one is associated with combination treatments and how they are currently assessed. This stems from the fact that combination treatments are evaluated as single technologies by health technology assessment (HTA) bodies but in fact contain multiple treatments that are priced independently and, in many cases, owned by different manufacturers.

As the use of combination treatments extends the amount of time a patient is free from disease or has stable disease, the backbone treatment is often used for longer. This alone can increase the cost of the combination treatment to the healthcare system and push it over the system threshold, even before the cost of the new add-on treatment is considered. This is made even more challenging due to strict competition law, which prohibits and restricts discussions between pharmaceutical companies on commercially sensitive topics such as pricing and reimbursement.

In 2019, an Australian research ethics organisation, the Bellberry Group, convened an international group of HTA experts and representatives of HTA bodies to discuss the challenges associated with valuing and paying for combination treatments, specifically in oncology. The report emphasised the scale of the problem and identified the need for further work to develop solutions.

‘Combination treatments are comprised of a ‘backbone’ treatment, often considered to be the existing standard of care, combined with a new ‘add-on’ treatment’

Thankfully, since then there have been various stakeholder groups looking at the issue including the Association of the British Pharmaceutical Industry (ABPI), the Office of Health Economics (OHE) and the European Federation of Pharmaceutical Industries and Associations (EFPIA).

This is a complex problem, with multiple processes and frameworks to consider. Takeda has a long history of tackling complex challenges, so we embarked upon the challenge to take this issue out of the ‘too hard to fix’ box. Throughout our work, which started in 2016 with a Westminster roundtable, we have been guided by our commitment to put patients at the forefront of everything we do, and this has driven our determination to find a solution for this problem.

As a result, we have co-developed two White papers which set out a proposed comprehensive solution for improving access to combination treatments. Collaboration was key to ensure the proposed solution was transactable and implementable whilst meeting the needs of all key stakeholders, so we partnered with experts from the patient, clinical, legal and academic communities throughout the development of the proposed solution. We also sought input from experts from NHS England and NICE on the key requirements. Below I outline our proposals, an Attribution of Value Framework and a Voluntary Arbitration Framework, and how they aim to overcome the key issues associated with the combination treatment access challenge.

The Attribution of Value Framework aims to address the cost-effectiveness barrier of combination treatments by proposing an economic methodology that proposes a division of value across the individual treatments in a combination. It does this by assigning a relative value to each treatment based on its health benefit.

This Framework is grounded in the standard rules of health technology assessment and designed to make use of the same information that NICE uses currently to undertake its appraisals of treatments. The methodology is independent of price and rather focuses on the value of a treatment as measured by a Willingness-to-Pay Threshold (WTP) per health gain.

WTP is a term economists use to determine the maximum allowance a healthcare system is willing to pay per health gain. Whereas health gain is measured using a standard metric called the Quality Adjusted Life Year (QALY).

This work aims to advance the objective of researching and developing methods of value attribution that was set forth by the Bellberry group (mentioned earlier). The Attribution of Value Framework is also intended to be used in conjunction with the Voluntary Arbitration Framework, which is detailed below.

The Voluntary Arbitration Framework proposes a standard operating procedure to support compliant dialogue between pharmaceutical companies on the attribution of value across individual treatments in a combination, ie the output of the Value Attribution framework described above. This process is proposed to occur alongside existing HTA and commissioning processes.
  
To address concerns around inter-company dialogue on sensitive topics of pricing and reimbursement and to address the competition law hurdles, this Framework proposes the use of ‘clean teams’. These are a construct used in merger and acquisitions to manage sharing of sensitive information between businesses. Employing clean teams would ring-fence the information divulged during the arbitration process and avoid the dissemination of sensitive data to the wider businesses.

The Framework also proposes the appointment of independent Arbitrators who would use their expertise to help facilitate discussions between manufacturer clean teams, and in the case of an impasse, offer a recommended value attribution.

To our knowledge, this is the first comprehensive solution to be proposed covering both an economic value attribution methodology and a practical framework for outlining a compliant process for inter-company dialogue. We recognise that, despite efforts to create a solution which addresses the many issues of combination treatments, there is of course outstanding change required for solutions to work.

For example, due to the unique challenge presented by combination treatments, we would argue that any solution will require the ability to utilise non-uniform pricing for the component treatments and we have proposed this in our solution. Without uniform pricing, a negotiated deal for the components of a combination would also impact the price of the component treatments when used, for example, as monotherapies for other indications and are potentially competitors. Non-uniform pricing would enable a bespoke arrangement to only apply to the combination in the specific indication and would address this competition law hurdle.

We also propose that any solutions that are implemented to address the combination treatment challenge become embedded into an industry-wide agreement, such as the ‘Voluntary Scheme for branded medicines’, to encourage universal participation of the pharmaceutical industry, the NHS and the wider healthcare community. As many pharmaceutical companies have combination treatments in their pipeline, with either a backbone or add-on treatment, we believe there is benefit to all to have a process that the life sciences industry has signed up to.

Under this proposal, pharmaceutical companies would commit to participate in the process with good faith but reserve the right to withdraw from the arbitration at any point should a deal not be deemed acceptable.

Takeda’s proposed solution intends to serve as the starting point of a discussion from which we hope to generate dialogue, receive feedback and stimulate further thinking to ultimately help to define a solution which can be adopted by all stakeholders and in all market archetypes. We are aware of other groups who are also working to develop solutions to the issue of combination treatments. We welcome all work on this complex issue and believe that every proposed solution adds to the discussion and will bring the community closer to solving this important issue and gaining access for patients to these treatments.
I gratefully acknowledge the kind assistance of my co-authors, the advisory panel members for their expert input and colleagues at Takeda UK Limited that helped co-create the concepts outlined in the paper. I genuinely hope that we can make a breakthrough to help ensure that novel combination treatments get to the patients that need and could benefit from them as rapidly as possible.

For further information on this combination treatment solution, please visit:
https://www.takeda.com/en-gb/what-we-do/combination-treatments/

Tanja Podkonjak is Director of EUCAN Oncology Access and Reimbursement Policy at Takeda UK