True patient-focused research

True patient-focused research through decentralised and hybrid trials

How can pharma improve the patient-centricity of its trials during COVID-19 and beyond? Experts from across the sector give their thoughts on the key approaches and technologies that are driving patient engagement forward.

With COVID-19 presenting new barriers to running and recruiting for clinical trials, making studies patient-centric is more important now than ever before.

According to one analysis, conducted by Global Data, approximately 67% of trial disruptions during the early stages of the pandemic were due to the suspension of enrolment, followed by the delayed start of planned trials at 18.4% and slow enrolment at 14.4%.

Ensuring that trials are easy to access and don’t overly burden the patient is essential amidst these potential disruptions – but a truly patient-centric trial has benefits beyond enrolment.

Trials that are engaging and easy to partake in can lead to higher adherence, higher satisfaction, improved data quality and overall performance, and can even give participants a more positive view of the sponsor company in terms of their commitment to bring new treatments to patients.

Patient centricity has been an area of growing interest to the industry for a while now, however many are still trying to figure out what this means, and how it can be operationalised (including study design), for the benefit of the patient and the industry as a whole.

Defining and understanding patient centricity

Earlier this year ICON invited distinguished speakers to participate in a panel discussion on patient centricity, based on their global experience and varying stakeholder positions in the industry to gain further understanding on this key topic.

The panel’s patient advocate representative was Avril Daly, vice president of EURORDIS and CEO of Retina International Clinical. Meanwhile, Professor Orla Hardiman – consultant neurologist, professor of neurology, at Trinity College Dublin and consultant neurologist at Beaumont Hospital – gave a clinical investigator’s perspective, and Dr Anthony Yanni, senior vice president of patient centricity at Astellas, brought a pharma executive’s view to the table.

The speakers discussed the key aspects that can help make trials truly patient-centric, and their insights provide some strong guidelines for what sponsors should be considering that could potentially support keeping trials on track in these difficult times.

Generally speaking, patient participation in clinical trials has long been below where pharma would like it to be. In a 2019 survey analysing the barriers to cancer clinical trial participation, more than 75% of patients cited structural and clinical barriers as the reason for non-participation. Other statistics show us that no more than 3% of patients participate in trials.

Avril Daly suggested that there’s a job of education to be done by patient communities to keep up to date with medical developments and ensure they understand the implications and the requirements for those clinical trials. Patients, in general, are attracted to clinical trials because of the prospect of face time with the clinical experts.

“Nevertheless,” Daly said, “There is, unfortunately, still a lot of negativity around trial participation… there’s a guinea pig attitude… We need to provide communications that balance positive patient clinical trial experience and the potential to save lives with realistic education about the risks of failure.”

Likewise, Professor Hardiman said that she believes that clinicians need to be engaged more fully and to be educated about the benefits of trials. It has been her experience in neurology particularly that patient participation in trials corresponds to the enthusiasm of the clinician.

Patient engagement

Even with ease of access, though, keeping patients engaged in a trial can still be a challenge – with patient drop-out in studies often being as high as 30%.

Dr Anthony Yanni said that overcoming this challenge requires using patient insights to understand the trial burden on patients and caregivers. Basic solutions include avoiding collecting unnecessary data, helping patients get to the site and recognising that the patient burden extends to a burden to family and caregivers.

“If we don’t understand what it is like to be in the exam room with patients, we are missing a core part of the patient experience,” he said.

Professor Hardiman said that trials should never cost the patient or caregiver, and the logistics for reimbursement should be seamless.

Engaging the patient throughout the journey for improved outcomes

Hardiman also underlined the importance of the clinical team using their “soft skills” to be able to communicate with the patient, to boost trust in the process and help patients feel part of something that is of value not just for themselves or the community but for society. In her opinion the best results are achieved when everyone plays their part in creating a real connection between the patient and the overall objective of the study.

Daly added that ongoing communication with the patient was critical, even during “quiet times” when data is being collected. She said that checking in with patients regularly can prevent an information vacuum, which runs the risk of fostering cynicism or a negative reaction to the trial experience.

Another area of consideration discussed when thinking about how best to engage patients was the importance of cultural difference. Dr Yanni cautioned: “You can’t apply what you know about a patient in Nebraska to a patient in Beijing. The healthcare delivery systems are completely different, as are expectations. There are even cultural differences regarding patients’ interest in treatment.”

Decentralised and hybrid trials

Of course, there are all kinds of new barriers to patient access and engagement when social distancing and lockdown measures are in place across the world – and, as a result, the COVID-19 pandemic has accelerated the use of patient centric solutions to ease the burden of patient participation, in particular in-home visits for patient assessment.

The concept of decentralised and hybrid trials has been around for a while, but the execution, technology and compliance issues are still evolving – and even months into COVID-19 there is still a huge variety of approaches being deployed.

EB McLindon, senior vice president, sites, patients and decentralised solutions at ICON, tells pharmaphorum that for any decentralised or hybrid trial solution, creating an ecosystem that supports the patient is key to collecting quality, valuable data.

“At the onset of the pandemic there were two key areas of focus – patient safety and access to clinical research data at the site level,” he says.

“In many cases, this had to be accomplished by converting traditional study conduct (i.e. monitoring source documents at the site) to a more decentralised approach with the support of the regulatory authorities.

“Many pharma companies immediately engaged mobile research nurses to conduct in-home patient follow-up or wellness checks to support patient safety. Although mobile nursing has been available in the industry since 2003, there was a tremendous uptick in interest and deployment. Protocols and study operations were amended to allow for the nurse to deliver investigational products to the patient’s home.”

Another solution to assist with patient safety that was less widely utilised, but deployed nonetheless, was telemedicine. In some cases, this solution was coupled with mobile research nursing.

“During the initial outbreak of the pandemic, many sites were open but were not permitting onsite data monitoring. In other words, oversight and management of study conduct was very limited. In response, industry implemented many remote monitoring tools and processes to support the gathering and evaluation of valuable research data.

“As we look to the future, we anticipate more utilisation of a risk-based quality management approach and remote monitoring for data review. It is probably too early to see if these solutions, among others, are fully adopted to support reducing the site and patient burden on future studies regardless of emergency conditions.”

McLindon adds, though, that sponsors are more open to decentralised trials as a way of making trials more resilient in challenging times – although actual levels of adoption will depend on factors like endpoints under consideration, overall study design, investigational product safety profile, patient profile, and regional regulatory acceptance of decentralised technologies and processes.

“Many pharma companies are seeking ways to make their studies more resilient and minimise future disruptions. To that end, we see strong movement from a traditional site-based approach to a more hybrid trial approach – incorporating aspects of decentralised solutions (technology, process, techniques) rather than an adjusted attitude to go fully decentralised.”

Likewise, a CTTI study found that the majority of respondents (76%) – with a median age of 61 years – reported they would prefer to participate in a decentralised study using mobile devices over traditional ones, citing greater convenience and fewer in person visits.

Respondents reported they were willing to use a variety of technologies – including mobile apps, wearable devices, and ingestible sensors – provided they were comfortable, convenient, and easy to use.

In 2019, ICON conducted its own patient survey on decentralised trials and, as with other research, found most of the respondents were interested in having decentralised solutions included in their clinical trial experience.

ICON is now conducting a follow-up survey in Q4 2020, and McLindon says he expects patients’ desire for decentralised solutions to have increased.

The potential of wearables

A recent ICON whitepaper highlighted connected devices in particular as an example of a tool that can help decentralise trials, facilitate patient access to studies and boost engagement.

The rise in using connected devices is owed in part to the popularity of wearables in the general public, such as Apple watches and Fitbit devices. In parallel, there has been an emergence of “over the counter” medical grade devices and sensors that were designed with the patient in mind, meaning they are easy to use, and have good connectivity and simple data flows.

These devices also have the benefit of being able to monitor daily life activities, such as the ability to go shopping or walk upstairs and see how therapies affect these aspects of patients’ lives.

This allows sponsors to select measures that are more meaningful to patients – which has long been a goal of companies looking to improve the patient centricity of their trials.

This is particularly important in areas such as rare disease and disease of the central nervous system, where traditional outcomes assessments are generally accepted as not being sufficiently sensitive.

Similarly, cardiovascular clinical trials that use digital health technologies can provide continuous assessment of the quantity and intensity of activity throughout a patient’s day, creating a clinically important digital endpoint for heart failure.

In fact, in an ICON webinar survey included in the whitepaper, 17% of attendees found patients living with cardiovascular indications to most benefit from novel digital endpoints.

Providing options

McLindon concludes that it’s important to provide study participants with as many options as possible in order to reduce patient burden.

“We need to be able to make a patient’s participation in research no different than their standard of care journey – we need to be able to present clinical research as a care option that mirrors their current care options.

“Prior to the pandemic, we witnessed how home-based patient visits increased patient satisfaction, compliance, and retention. By offering patients options to participate in research, we increase the patient catchment area and provide more access to research for a diverse population.

“Innovations will continue to help evolve the overall trial process and further enhance the patient and site experience even after COVID-19,” he says, adding that he believes more patient-centric study designs are “here to stay”.

For more insights into best practice for patient-centred clinical trials, read the full Patient Centricity panel report, featuring more comments from all participants and data from ICON’s own research.

For further reading see the Digital Endpoints whitepaper, or take a look at ICON’s report on Agile Clinical Monitoring.

EB McLindon

EB McLindon is senior vice president, patient, site & decentralised solutions at ICON. Since joining ICON, EB has driven the development of the company’s site and patient strategy and led a large team of functions in the delivery of solutions including; Accellacare, ICON’s global clinical research site network, Symphony, ICON’s in-home health provider, patient recruitment and retention services and FIRECREST digital solutions. He is currently providing consultancy to help sponsors realise the potential of decentralised trials by developing the infrastructure, technology and operational framework for success. Previously EB had a key role in the development of Accelovance, a CRO that owns and operates clinical research sites.

ICON plc is a global provider of outsourced drug and device development and commercialisation services to pharmaceutical, biotechnology, medical device and government and public health organisations. The company specialises in the strategic development, management and analysis of programmes that support clinical development – from compound selection to Phase I-IV clinical studies. With headquarters in Dublin, Ireland, ICON employed approximately 15,250 employees in 94 locations in 40 countries as of 30 September, 2020. Further information is available at www.iconplc.com.

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