What's the outcome? Measuring the effectiveness of new treatments in clinical trials

Clinical trials are the only way to ensure that new treatments are effective. But how exactly does the process work? FInd out why 'outcome measures’ and ‘endpoints’ are crucial, and how SRUK funding is playing a key role in improving the measures used in treatments for scleroderma.

Clinical trials are the only way to ensure that treatments for Raynaud’s and Scleroderma are effective. But how do we judge whether a treatment is working? Outcome measures are needed to show us how well participants respond to drugs during clinical trials. COVID-19 has improved public knowledge of the trials process and its necessity for the approval of new treatments. All clinical trials are carried out to a strict and detailed protocol, which includes information on the outcome measures to be collected and the ‘endpoints’ to be examined.

These are fundamental for study design, and vital in showing that the treatment is effective and warrants approval for use; even determining how many participants to involve in the trial. But what are outcome measures and endpoints? And why are they so important in treating scleroderma?

Outcome measures and endpoints are closely linked. Outcome measures are changes in a patient’s status in response to the treatment; and many are collected during a clinical trial. Often, one or two of these measures are chosen as an ‘endpoint’.

Endpoints are examined at defined timepoints e.g. by comparing the status of a patient at the start of treatment and at the end. The ‘gold standard’ outcome measure used in diffuse cutaneous systemic sclerosis (dcSSC) is the modified Rodnan Skin Score (mRSS). Many clinical trials use as an endpoint a change in mRSS at treatment end, to show that the drug is effective.

The mRSS is a good measure of the effects of scleroderma treatments on affected skin. However, a new medication could offer other potential therapeutic benefits as well, which may not be obvious using mRSS alone.

To help overcome this, a ‘composite endpoint’, called the Combined Response Index in SSc (CRISS), was developed in 2016, using data from 150 patients with dcSSC. This considers multiple endpoints of multiple outcome measurements and combines them, to deliver a score that indicates a more holistic response to treatment.

In collaboration with The World Scleroderma Foundation, SRUK is funding two exciting international projects, which aim to understand the outcome measures that are mutually important to both patients and clinicians.  

Drs Alain Lescoat (FR) and Dinesh Khanna (US) are developing a combined response index for limited scleroderma (the CRISTAL index). There is a paucity of trials of new treatments for limited cutaneous systemic sclerosis (lcSSC), owing to a lack of relevant outcome measures. The CRISTAL study has the potential to change this.

In a separate project, Drs Del Galdo (UK), Khanna and Furst (US) are working on improving the CRISS, making it more reflective of how patients with dcSSC feel, function and survive. As well as the potential benefits for patients, this is also valuable to regulators in the approval of new therapies.

The impact of this work could be far-reaching, providing more reliable indicators of whether new treatments are working and are of benefit for patients. We look forward to updating you on the progress of these exciting projects.