1. Cross company dialogue

In the UK, when the medicines in a combination therapy belong to different companies, dialogue between the companies may be needed to determine a price that can be proposed to the National Institute for Health and Care Excellence (NICE) – the Government’s arms-length body which determines whether new medicines are value for money (clinically and cost effective). However, companies consider there to be a high level of risk in doing this, due to concerns about infringing competition law. Further guidance is needed to support pharmaceutical companies.

2. Health Technology Assessment (HTA) decision making frameworks

In England^[8], NICE determines whether a combination therapy is cost effective using the same framework as it does for individual medicines. The company who manufacturers the new component is responsible for submitting an evidence package to NICE for the combination therapy and pricing their component accordingly. The existing component(s) will already have a price agreed with the NHS that is not reconsidered during the evaluation process.

There are fundamental challenges with this methodology, some of which are technically complex. A key challenge is that by extending patients’ lives when they are treated with a combination therapy, the patient receives treatment for longer and the costs to the NHS increase. This increase in costs is not always seen as being cost effective - in some cases even when the new component of the combination therapy is priced at £0.

The issue of demonstrating cost effectiveness with combination therapies is also recognised internationally, as highlighted by the Bellberry Group’s international workshop in November 2019, where experts representing stakeholders from HTA agencies, the clinical community, academia, the patient community, and the pharmaceutical industry discussed the challenges and potential solutions to valuing and paying for combination therapies in oncology^[9].

3. Combination/indication specific pricing

Simple discounts that are uniform across a medicine’s different indications are the preferred NHS pricing arrangement. Flexibility can be considered in unusual or unique circumstances and NHS England’s Commercial Framework recognises combination therapies may require bespoke commercial solutions^[3]. However, the criteria for pricing flexibility can be very challenging for companies to meet. In practice, application of combination/indication specific pricing has been very limited and is not providing a predictable or consistent pricing approach.

The ability to do combination/indication specific pricing, so that any changes in price required for the components in the combination therapy do not affect their price in other indications, is a key enabler to supporting the commercial viability of many combination therapies.

4. Data for transacting commercial agreements

Combination therapy components are usually used individually and to treat other indications. To transact differential pricing agreements, sufficiently granular prescribing data is required to understand how many patients have been treated with the combination therapy and for how long.

5. Value attribution

Ideally, the components of a combination therapy would be priced relative to the benefit they offer when they are used in combination. Attributing this value to each component is however not straight forward and may not able to be supported by comparative clinical trial data.