New Study Finds Patient Data Could Help Minimize Placebo Groups in Clinical Trials

When it comes to developing new medicines for Duchenne, creating good drugs is of course paramount. It is also critical, however, to design good trials to test those drugs. And improving how we design clinical trials is potentially a very big way to impact speed and success when developing new drugs. A group known as “cTAP” (short for the collaborative Trajectory Analysis Project) is working diligently to do just that. And they just released some important new findings. 

Published in the journal Neurology, the study provides insights that help answer a key question for Duchenne clinical trial design: Can we be smarter about how we use data to minimize the need for placebo groups in clinical trials? Are there alternative ways to get important comparison data demonstrating what happens to patients who do not get the experimental treatment?

cTAP explored this question for Six-minute Walk Distance (6MWD), a commonly used outcome measure in clinical research that evaluates how far someone can walk in six minutes. And the answer, supported by cTAP’s rigorous and thoughtful analysis, is yes. But much now depends now on how these findings get applied in practice. Charley’s Fund President and COO Laura Dalle Pazze sat down with cTAP founder Susan Ward, PhD, to discuss the findings and help raise awareness of the research, the results, and what this means for making things happen better and faster for people with Duchenne.

Laura Dalle Pazze: Thank you, Susan, for championing this effort and taking the time to help us highlight the study’s findings and understand their impact in context. You know we’re big fans of opportunities to help research move forward faster and more effectively.

Susan Ward: I appreciate the chance o speak with you. cTAP’s mission is to find solutions to critical problems in drug development by learning from patient data. Our founding priority is to help companies developing drugs for Duchenne. We have a powerful international alliance of Duchenne companies, physicians, nonprofits, and a highly skilled network of statistical experts. We work together to pool resources (data, funding, brainpower) and identify and solve problems. I’m grateful for the chance to help more people learn of our work – and how it is being used it to drive to faster results for patients.

LDP: Tell us first — what was the goal of this study?

SW: We wanted to answer the question: “How does natural history data (NH) of disease progression compare to placebo arm data found in clinical research in DMD?”

LDP: Say more about what that means and why it’s important.

SW: First of all, it is important to understand the two types of data. Natural history data is usually collected during routine doctor visits. It tracks and tells us about a patient’s health over the course of his or her life without any particular clinical trial intervention. Placebo arm data is the data collected in the context of a clinical trial but specifically from those patients who receive a placebo instead of an active medicine. Placebo arm data is collected in a highly regulated, pre-planned context. People know they’re being measured for a specific purpose, and some experts question whether this impacts the results.

We set out to evaluate whether there is a meaningful difference between data tracking how patients progress when participating in a placebo arm of a trial and how they progress over the course of normal life. This is an important question to answer for a few reasons. First, clinical trial participation is a big burden for patients and families. If we’re going to ask patients to commit to being in a trial and not receive the experimental treatment, we need to be sure that’s necessary. Meanwhile, minimizing the number of patients in the placebo arm, as long as it is a scientifically sound solution, is also important for drug development companies because it saves time, money, and effort on their side too.

If we can demonstrate that the two types of data are the same, we can consider opportunities to use natural history data to design better trials. But first it was essential for us to do a rigorous analysis with reliable data to make the case.

LDP: So cTAP found the data and did the work to answer this question. Tell us about the results.

SW: Plain and simple, the results showed no significant differences in disease progression between patients in routine clinical care versus those in the placebo arm of a clinical trial.

LDP: We know it’s crucial that the analysis that led to these findings be rigorous, relevant, and unimpeachable. Can you tell us more about how you designed the study?

SW: Certainly. We wanted this study to be of the highest possible quality, which meant that we needed to analyze disease progression from very large numbers of patients and conduct an analysis using rigorous statistical methods. In the study, our researchers analyzed 6MWD scores of 383 patients who had been placed in the placebo arms of six clinical trials. We compared the results with the 6MWD scores of 430 patients from five clinical registries in the U.S. and Europe.

LDP: Why did the study use 6MWD?

SW: 6MWD was a helpful starting point because it has been used so often historically. The vast majority of clinical trials that include a placebo arm have used 6MWD as the primary test to measure drug efficacy. But it was just a starting point, and we need to replicate these findings in other measures. For example, in recent years, many trials have used the North Star Ambulatory Assessment (NSAA). Now we have an opportunity to do a similar assessment using NSAA as the outcome measure in question.

LDP: Before we get ahead of ourselves, we understand that we can’t jump immediately to eliminating all placebo arms based on these findings. Can you help us better understand why?

SW:  It’s a bit like building a house. Houses can be built in all sorts of shapes, styles, and sizes. But what they have in common is they all need a strong foundation, and they all need sound principles guiding their design and construction. No one wants a house that looks super cool but then falls down. Similarly, clinical trials can be designed in different ways, but they need a strong, data-driven foundation, and data-driven principles that ensure any ‘customization’ is also sound. Our study was designed to develop a foundation and strong principles that drug developers and regulators can rely on when designing their clinical trials and methodology for comparing treated and untreated patients.

LDP: But should patients and families still take heart that this work can be applied in immediate ways to improve what’s done?

SW: Absolutely. Overall, we hope these results will allow for better and smarter trials in DMD that deliver an unambiguous assessment of the efficacy of a new therapy. More specifically, the results of this study should increase confidence in using natural history patient data to design better clinical trials in the first place, give better context for interpreting results, and potentially then to reduce the number of patients needed for placebo arms in trials.

LDP: What’s next for your work to help translate this finding into real-world application?

SW: Our next step is to meet with regulators (starting with the FDA) to review the results and assess how these findings might influence clinical trial protocols moving forward.

Regulators have a special opportunity here too. Because they see every clinical trial that drug companies conduct, they are uniquely positioned to detect patterns and develop insights others cannot. The more closely we can work with the regulators to review the results of this study, the sooner we can get their input, ideas, and questions. And the sooner we have that the sooner we can begin research to address any questions they have.

We are also eager to replicate this effort in other outcome measures, including ones that would expand the help to boys who are no longer able to walk and perform tests like 6MWD. We need to make sure we have ways to speed research for all boys and young men with Duchenne.

LDP: Is there anything else you want patients and their families in particular to know?

SW: Yes, thank you for asking. This study is a testament to the power of collaboration between all segments of the community. It’s the largest collaboration ever attempted between so many clinical experts in DMD. But most importantly, it highlights the crucial role that patients play in permitting their data to be used for research – without the generosity of patients and their families, this study would not have been possible.