Outcome measures: Patients beyond endpoints

Pharmaceutical companies face increasing pressure to demonstrate not only the efficacy of their treatments, but also the impact of these treatments on patients' lives. This interest in and the evolving regulatory requirement to put patients at the centre of the drug development process – patient-centric from end to end – means pharmaceutical sponsors must design clinical trials with patient-centred outcomes in mind.

To discuss the importance of outcome measures further, pharmaphorum spoke with Sonia Bothorel, Managing Director of Mapi Research Trust and Outcome Measures Solutions, a leader in the distribution and facilitation of clinical outcome assessments.

Three key reasons outcome measures matter

‘Outcome measures’ refer to a multi-faceted approach to identifying, selecting, and implementing evidence-based measures that matter to patients. Simply put, they are the various measures researchers can focus on to assess a treatment’s efficacy. While endpoints define the goals, such as specific events or outcomes that are used to determine the success of a trial, outcome measures provide the data to determine if those goals were met.

“Endpoints are really specific, measurable events or markers that demonstrate the effect of a treatment that determines if a trial succeeds or fails,” explained Bothorel. “Outcome measures, on the other hand, provide a more comprehensive and broader set of measurements, tracking various effects and viewing the treatment impact on the daily life of a patient. For example, an endpoint could be a reduction of 50% in the tumour size at six months, whereas the outcome measure could be patient pain levels or daily function scores.”

“[Focus on outcome measures] is really important for three main reasons,” continued Bothorel. “The first one is – every patient, every disease is different. Therefore, it is important to ask patients what matters to them, quantifying side effects versus efficacy, to have this holistic view of the impact of the treatment. Patient needs, preferences, and concerns should drive the innovation and creation of new therapies.”

The patient voice is very much needed in the evaluation of treatments because clinicians may not know what the impact of disease and its treatment is on patient daily life or – importantly – their quality of life. Patient-centred drug development ensures that patients are included, so that drugs developed address the real-world needs and experiences of patients, and are not simply only meeting clinical endpoints, such as biomarker changes or survival rates.

“The second reason […] is that [an outcome measures] approach leads to more patient-friendly trial design,” noted Bothorel. “This increases patient engagement and adherence, which is important, of course, for clinical trial success and for regulatory acceptance.”

“The third reason […] is that regulators are increasingly valuing patient-centred evidence, with the FDA's Patient-Focused Drug Development (PFDD), and EMA guidance being released on Patient-Focused Drug Development,” she said. “Patient-centred trial design can accelerate the approval process. PFDD is a shift in the way that drugs are developed now, systematically incorporating patient participation in all stages of medicine development […] Regulatory bodies worldwide are now really pushing to ensure clinical trials are more patient centric.”

Digital health technologies, patients, and regulatory requirements

Indeed, there is growing demand from regulators and patients alike for pharmaceutical companies to show that new therapies meet clinical endpoints and also deliver improvements in patients' quality of life and lived experience. In line with this, sponsors increasingly seek to develop endpoint assessments based on combined clinical outcome assessments (COAs) and digital health technologies (DHTs) data to enable more optimised protocol and patient-centric study designs.

The FDA definition of COA is a measure to describe or reflect how a patient feels, functions, or survives. They provide a structured way to measure the quality of life for patients. Patient-reported outcomes (PROs) specifically capture the patient’s direct perspective on disease burden, treatment effects, daily functioning, and overall well-being. Such insights cannot be captured by traditional clinical endpoints, such as overall survival rates or disease progression.

The increasing use of digital health technologies that remotely, passively, and continuously collect participant data are a significant advancement for clinical trials and have been instrumental in this rise of patient-centred clinical trial design.

“DHTs enhance our ability to capture a vast amount of real-world data, improve patient engagement, [and] ease recruitment of difficult-to-reach patients, […] increasing diversity in clinical trials, and delivering more meaningful results with better detection of rare events [and] less missing data,” explained Bothorel. “In addition, it can reduce cost for fully automated data collection.”

“For example, in sleep disorder trials, wearable actigraphy devices are being used to provide objective measures of sleep patterns,” Bothorel continued. “These devices can track movement traits, and wake time, offering a more comprehensive picture of a patient's sleep quality than traditional sleep diaries or questionnaires alone.”

“Another example could be the use of a smartphone application for tracking patient-reported outcomes in oncology trials to capture the patient experience with side effects. These apps can send daily prompts for the patient to report their level of pain, fatigue, nausea, or other relevant symptoms. This real-time reporting not only provides more accurate data, but also allows for timely intervention if there are several symptoms that are reported.”

“Another example could be in Duchenne disease: traditionally, there is a six-minute walk test (6MWT) that is a COA gathering data regarding the gait,” she said. “The DHT component will be very helpful to complement the informative data on gait, instead of only having a COA. That's why I think the combination of COAs and DHTs will be really valuable for the future.”

The ICON Outcome Measures solution

ICON’s newly launched Outcome Measures solution offers a full-service approach to support sponsors in the identification, selection, and implementation of measures that matter to patients, from phase 1 through regulatory approval.

The solution provides an advisory capability on the optimal COA strategy for a study and drives operational delivery of integrated end-to-end solutions that incorporate the selection of actively and passively collected COAs, eCOA technology, COA licensing and distribution, and language services. Its suite of capabilities also includes regulatory and advisory consulting, technology tools, data, and services to support sponsors in making evidence-based and informed decisions on protocol design to reduce patient burden, increase engagement, and enhance data quality.

“Outcome Measures is a collection of end-to-end services,” explained Bothorel. “Launched in September 2024, this end-to-end solution is designed to help clinical trial sponsors identify, select, and implement evidence-based measures that matter to patients. We have a range of services, including core strategy and strategic services, to assist in selecting [and] incorporating COAs in clinical trials.”

“We have COA databases in the ePROVIDE platform and another platform called Atlas for DHTs,” she continued. “We have, of course, COA licensing and distribution in collaboration with the Mapi Research Trust Organisation. Mapi Research Trust is the exclusive distributor of more than 800 COAs. We have, as well, eCOA implementation services and all the translation and linguistic validation services associated to that. As you can see, it's a complete suite of services to support the entire life cycle of patient-centric drug development, from the strategy to the implementation.”

“The most important thing to keep in mind here is that there is an increasing trend regarding including patient-centric assessment in clinical trials and even more [so] in healthcare delivery. ICON is delivering this full suite of services to ensure that patient-centricity is taken into account in the development of clinical trials,” Bothorel concluded.

For more information on Outcome Measures, please visit www.iconplc.com/solutions/outcome-measures.

About the author

Sonia Bothorel currently serves as the Managing Director of Mapi Research Trust, an industry leader in the distribution and implementation of Clinical Outcome Assessments in global clinical trials. At Mapi Research Trust, Sonia leads a multinational team of 140 employees across operations, sales, marketing, technology and pharmaceutical sciences, and oversees the organisation’s varied revenue streams. A seasoned life sciences executive, she also leads the Outcome Measures practice within ICON, which combines COA data and digital endpoints to enable optimised protocols and patient-centric research. Prior to Mapi Research Trust, Sonia held positions in manufacturing in the pharmaceutical and food industries, including at Nestlé Corporation. She has more than two decades of experience spanning operations, business management, clinical research, and corporate leadership. Sonia holds an Executive MBA from France’s EM Lyon Business School, where she also is a Board Member.

About ICON

ICON plc is a world-leading healthcare intelligence and clinical research organisation. From molecule to medicine, we advance clinical research providing outsourced services to pharmaceutical, biotechnology, medical device and government and public health organisations. We develop new innovations, drive emerging therapies forward and improve patient lives. With headquarters in Dublin, Ireland, ICON employed approximately 42,250 employees in 106 locations in 55 countries as at September 30, 2024. For further information about ICON, visit: www.iconplc.com.