NIRG: Patient and public INvolvement In target differeNces in Trials (The PINpoINT Study)

Clinical trials are considered the best way of testing which treatments are made available in the National Health Service (NHS). Trials are run to benefit patients and so patients should be central to their design. Even though patient and public involvement (PPI) is considered important, patients and the public rarely have a say in key trial numerical aspects (for example, how big of a difference we look for when testing treatments).

We aim to co-design new methods and tools to improve the involvement of patients and the public in a key numerical aspect in trial design and interpretation - the target difference.

A "normal" (superiority) clinical trial tries to find out whether a new treatment is better than the current treatment. A non-inferiority trial tries to show the new treatment is not worse than the current treatment (but it may have other advantages, like lower cost or better safety). To make a treatment recommendation, new treatments need to be better or good enough by a certain margin.

This is called the target difference. Most trials aim to detect a target difference that is important to relevant stakeholders, but they often exclude patients from decision making.

For example, we may have a trial testing drug A against drug B to treat pain in patients. To decide if drug A is better than drug B, we will have to define a target difference in the patient reported outcome (pain). In this example pain is measured by asking patients "How much pain do you feel today?" in a scale of 1 (no pain at all) to 10 (a lot of pain).

The trial may aim to detect a difference of 2 points in the pain scale after 10 days of being in the trial. This means that if participants in the drug A group had a score of 3 points in the pain scale and participants in the drug B group had a 5.5 score, we would decide that drug A is a better treatment.

But is that a worthwhile difference to patients?

Currently, target difference decision making is usually based on (informed) guesswork based on a small team's judgement which often excludes public partners (defined here as patients or members of the public part of the research team). Including patients and public partners would ensure trials consider patient important differences when they are designed.

This would inform the target difference along with other considerations, like the trial's costs and clinician's views. It would also support the interpretation of trial results that help inform which treatments are available in the NHS. To achieve this, we propose to:

- Work with patients and public partners to develop inclusive tools to (a) support a common understanding of target differences in the research team; (b) enable an efficient identification of patient important differences at the trial design stage; and (c) enable a meaningful discussion of existing target differences with public partners ahead of deciding the final target difference for the trial. We will identify and use current practice to support the design of these tools.

- Pilot the full process - from identification of available target differences at the start of trial design, to a final meeting with all relevant stakeholders in the trial team including public partners, where consensus about the target difference is reached

- Assess the feasibility, and impact of involving patients and public partners in deciding the target difference and draft guidance for trialists and public partners considering the findings

Patients and public partners do not need to have a prior understanding of medical statistics to get involved. The tools will be developed to be understandable and accessible to people with different numeracy levels. Our project has been developed and will be informed by an advisory group including three experienced public partners.

Ultimately, the tools developed in the project aim to improve the relevance of trials and reduce research waste by making patients the foundation of clinical research.