28 Sep 2022

Good guidance for good trials

Good guidelines are needed to facilitate the generation of reliable answers to important questions about the benefits and hazards of medical interventions, says Professor Sir Martin Landray

You were appointed in 2019 to lead an initiative to develop new guidelines for clinical trials, now known as the Good Clinical Trials Collaborative. What motivated you to take on the role?

As a scientist and doctor, I’ve always had an interest in public health and the broader issues impacting it. Large-scale randomized trials are fundamental to knowing which treatments work and which don’t. While randomized trials have been around since the 1940s, they have become increasingly expensive and burdensome to run with a huge escalation in costs and complexity over the past few decades. I find that deeply worrying because without sound knowledge of the safety and efficacy of a treatment, medicine becomes little more than educated guesswork.

One of the reasons why trials have become more difficult to conduct is that the rules and guidelines are no longer fit for purpose. Written decades ago, many of the guidelines and rules have constrained the ability of trials to adapt to a changing world – over that time there have been huge changes in information systems, communication technology and healthcare. As for guidelines, none of them actually focused on the key principles that underpin what mattered in a trial. Rather, the emphasis was on who should do what, how they do it, and where they write it down, mistaking more documentation for better quality.

I had been examining the problem for many years. What struck me was these historic rules and guidelines weren’t focusing on the primary objective of a trial, i.e. providing a compelling answer to an important question – an answer that could truly be relied on from a drug development, patient or public health perspective.

As such, I was delighted when, in 2019, Wellcome and the Bill & Melinda Gates Foundation invited me to lead an initiative to develop and promote a new approach to clinical trials regulation.

What is a good trial and what is good guidance?

First and foremost, we need to focus on principles, not the process. Processes change all the time, but principles stand the test of time. Ten years from now, the way trials are conducted will be very different from how they are done today, or in the past. Unlike existing rules and guidelines that tend to focus on the process, good guidance must be grounded on principles. Trials that adhere to good, principles-based guidance will protect the safety and wellbeing of trial patients and generate results that can be relied on to treat future patients.

Over the past two and half years, the Collaborative has led the development of new guidance that involved input from a global community of experts and stakeholders from diverse sectors, organisations and backgrounds, including patient and public groups from higher and lower income settings. The Collaborative’s approach is to create something that will guide people to think critically as opposed to telling them what to do or constrain innovative approaches. It aims to help focus on what matters for a good trial, rather than what has become common practice, regardless of its value.

The clinical trials landscape is rapidly evolving. Amid the changes, how will the Collaborative’s guidance continue to provide support?

In addition to prioritising results and people, clinical trials should be run as efficiently and practically as possible. Today, trials are conducted across different settings and contexts in all parts of the world. As we speak, there are vaccine trials being run in Sub-Saharan Africa, cardiovascular prevention trials in China, mental health therapy trials in the UK, rare disease trials in the US, and so on. While we may be dealing with different health systems and types of patients, our fundamental aim of producing reliable results for future patients while protecting those taking part in trials remains unchanged. Good guidance is flexible, fosters critical thinking and promotes the development of proportionate approaches for each and every randomized clinical trial.

What are your ultimate goals for the Collaborative and its guidance?

If we are to change the ecosystem so it is easier to evaluate what works and what doesn’t, a number of things must happen. Existing rules and guidelines need to be re-evaluated and, in many cases, simplified so that they genuinely guide. Many international government and health bodies, including the WHO, G7 and ICH, have acknowledged the problems and are taking steps to upgrade their guidelines. We are privileged to be in discussion with many of them on how our guidance could support their effort.

We will also provide training and support on how to interpret and apply the principles. As new technologies and innovations emerge, we will support those designing and conducting trials in understanding what their impact might be and how they could be applied to trials. Importantly, through our work, we aim to build confidence in the system among all stakeholders, including those who design, regulate and participate in trials.

Collaboration, openness and transparency are also key. Therefore, in line with our name, the Good Clinical Trials Collaborative, we will seek to foster greater collaboration and sharing of knowledge, experience and expertise within the system.

If you have just one advice, what would it be?

Invest the time to identify the question, the one you really want the trial to answer, and the audience that has to be convinced by that answer. Get as much advice and input from a variety of stakeholders. It may be easy to come up with the question but do not forget to consider the nuances. The answer should be one that will reliably inform the development of new medical interventions and the care of future patients. Ultimately, think of the most efficient and effective way to make the journey from a great question to a compelling answer.

Good guidelines are needed to facilitate the generation of reliable answers to important questions about the benefits and hazards of medical interventions.
Professor Sir Martin Landray
Good guidance for good trials Professor Sir Martin Landray