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PATIENT-CENTRIC CLINICAL TRIALS

How language and tech are re-shaping clinical trials today?

Nimita Limaye, SVP, Strategic Partnerships and Medical Writing, CSOFT Health Sciences

This article elaborates upon the meaning of ‘patientcentricity’, and touches upon industry trends, evolving regulations and organisational strategies to develop a ‘Patient Focused Drug Development’ strategy, and the best practices and metrics used to define success. While technology has clearly been a game-changer in enabling a ‘patient-centric’ approach, with trials shifting focus from the site to the patient’s home, the industry is grappling with the need to ensure the ‘patient-connect’. This article discusses different strategies for driving patient-centric clinical trials, including the importance of listening to the patients needs and engaging with the patient in the right way..

So, we’re spending US$2.6 billion on bringing a new drug to the market (FDA News, 2014) and we’re spending about a dozen years to do so. That is a lot of time and money spent! For whom are we doing all this, again? The patient, yes, of course! But are we really listening to the patient’s voice and addressing the patient’s needs? The right to self-determination is the consequence of a free society. Yet is the patient a passive recipient of healthcare decisions made by the investigator and the sponsor, or can patients be active participants and participate in the decision-making process and improve their own clinical outcomes? A report published by The Economist Intelligence Unit (commissioned by PAREXEL) demonstrated that the patient-centric approach resulted in not only doubling the number of patients being recruited, but recruitment took half the time. In addition, the drug was 19 per cent more likely to be launched in these trials. Surprisingly enough, only 5.2 per cent of phase II-III trials followed this approach (EIU, 2018).

The industry is waking up, albeit a little late, to the need to drive patientcentric clinical trials. The ‘Chief Patient Officer’ is a new term that has come into existence as the industry adapts to the ever-evolving model of clinical trials and pharma companies are now taking measures to engage actively with patients. Bristol-Myers Squibb, for example, is soliciting patient inputs on their protocols, that include, among other things, the inclusion and exclusion criteria; and Ipsen Biopharmaceuticals seeks patient’s inputs from the start of the clinical trial set up and has adapted protocols based on patient’s inputs (Round and Williams, 2018). Merck has attempted to enhance patient retention by having at-home sample collection kits to minimise the patient burden. It is conducting conversations with subject matter experts to enhance its cultural competency and develop outreach tools. It is also monitoring enrolment data by ethnicity to enhance patient diversity and has focused on enhancing minority and ethnic representation (African Americans, for example, represent less than 5 percent of the clinical trial population) (Nissen and Geday, 2019).

With a similar objective in mind, Janssen conducted trials like GRACE (Gender, Race and Clinical Experience) and LOTUS, using social media, imagery and educational materials, and arranged for transport and chose sites so as to optimise inclusion. In addition to recruitment, patient retention is of prime importance. With one-third of patients dropping out of clinical trials, companies are investing in diverse initiatives to enhance patient retention. Janssen Pharmaceuticals has gathered feedback from over 1,700 trial patients in 19 countries to better understand patients needs and has launched Health Caring Conversations for Clinical Research, to drive science-based patientcentred conversations. It has also integrated concepts such as telemedicine, ‘Direct-to-Patient’ (DTP) shipment of drugs, collection of samples from patient’s homes and the use of platform solutions and wearables to take trials to the patient’s home (Levine, 2019). In fact, it is running two virtual clinical trials. The Heartline Study, which is the largest randomised trial on heart disease in history, which will run for three years on 150,000 patients, all above 65, uses the Apple Watch ECG application and the Apple’s iPhone Health app (Hale 2020). The CHIEF-HF is the first virtual trial to evaluate a new indication for Invokana (canagiflozin – a drug earlier approved to treat diabetic kidney disease). The trial which is to be conducted on 1900 patients leverages an innovative mobile clinical trial platform, and wearables and  will assess the quality of life and track physical activity of people with heart failure with or without type 2 diabetes. It follows a patient-centric approach and will not only take the trial to patient’s homes, but will also return patient’s their own data to help them understand how treatment and lifestyle choices affect their health. (Janssen, 2019).

Sanofi conducted a fully virtual phase IV clinical trial, VERKKO, using a wireless glucose meter to monitor diabetes, using things like e-consenting, and successfully recruited 60 patients (average age 56) via Facebook. More importantly, the patient satisfaction score was 4.52 out of 5, demonstrating the success of this patient-centric approach (Limaye R et al, 2018). Sanofi has also worked with patient advisors, standing-in as subject matter experts, representing patient groups. Leveraging their input at an early stage, has helped Sanofi design trials focused around the day-to-day lives of patients, and decrease the number of patient visits and significantly bring down the number of protocol amendments as well (ACRP, 2016). In a patient-centric approach towards oncology clinical trials, Pfizer launched the Living with Cancer initiative, which includes the LivingWith™ app which assists people manage their lives track how they’re feeling, and communicate with loved ones.As a part of the Pfizer Oncology Together program, Pfizer arranges for dedicated ‘Care Champions’ with a social-work background to deal with a lot of procedural, emotional, logistical and financial complexities. Pfizer also runs a patient gratitude program to acknowledge patients’ contributions. (Schmeltz, 2018). The FDA’s Oncology Center of Excellence (OCE) launched an initiative called Project Patient Voice to create a publicly available information bank describing patient-reported symptoms from cancer trials for marketed treatments and Astra Zeneca became the first company to participate in this initiative contributing patient data from its ongoing AURA3 trial for locally advanced or metastatic non-small cell lung cancer (Ray, 2020).

Some of the important aspects of designing a patient-centric clinical trial include:

  • Obtaining patient’s inputs into the Target Product Profile (TPP), the blueprint of the product label
  • Obtaining patient’s inputs into protocol design – ‘crowd-sourcing’ of protocols, to find out what works best for patients, from patients. Transparency Life Sciences has developed a platform ‘Protocol Builder’, which enables patients and physicians to share their inputs in the protocol development process and this platform is being used to develop trials for irritable bowel disease, Parkinson's disease, and multiple sclerosis (Carlson, 2014). It is believed that the most successful trials of the future will be designed by patients
  • Obtaining patients insights at all stages along the patient journey from TPP to product label
  • Identifying end-points that are important to patients – establish meaningful benefit to patients. Patients know what matters to them – what makes a difference to their lives. This has been highlighted in the U.S. Food and Drug Administration’s (FDA’s) Guidance for Industry on Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims (Dec ‘09). ICH E8 (R1) (May 2019)also stresses upon the importance of obtaining patient input in the design, planning and conduct of clinical trials
  • Recognising that it’s not only about quantitative research: qualitative research also matters. Personal interviews, focus groups, etc help better understand the patient’s point of view
  • Ensure that content validation of Patient-Reported Outcomes (PROs) is based on patient’s inputs. PROs are questionnaires which obtain the patients point of view on the impact of the treatment on their symptoms, their quality of life, treatment satisfaction, or the impact of the treatment on their daily life
  • Understanding ‘what is the most burdensome aspect of the disease?’
  • Ensuring that the most relevant ‘current’ needs of the patient are being addressed as patients’ needs are also evolving
  • Conducting ‘mock’ trials. Running a ‘day in the life of a patient’. Putting yourself in the patient’s shoes – and figuring out whether you like what you are experiencing. If you perform UAT for a software application before launching it to ensure that end-user’s requirements are being met, shouldn’t we be doing the same for patients?
  • Enhancing patient education. Knowledge drives empowerment – leads to better decision making. This allows patients to have a better control over their health and also improved adherence
  • Use the right level of health literacy. The Patient Protection and Affordable Care Act of 2010, Title V, defines Health Literacy as ‘the degree to which an individual has the capacity to obtain, communicate, process, and understand basic health information and services to make appropriate health decisions.’ It is recommended that health information should be communicated in lay language so that an 11 – 13-year old (6th – 8th) grade literacy level) cab understand it. Microsoft Word’s Flesch-Kincaid grading scale recommends a readability score (reading ease) of 60 – 80. This is impacted by the length of the words and sentences used and by the percentage of passive sentences used. Short, sweet and simple is the way to go! All medical jargon should be avoided and scientific terms should be broken down into simple, lay language. The active tense is recommended. Images and pictograms if used, should be simple. Only relevant information should be included and it should be contextual
  • Ensuring that you are communicating with the patient in the right language, at the right time, using culturally sensitive communication
  • Facilitating logistical needs - with 70 per cent of patients staying more than 2 hours from the trial site, it can be challenging for a patient to participate in a clinical trial. Traveling to a site would be even more difficult for patient’s that are aged, frail, are children, or have infants. Arranging for a concierge to help with travel to the site or managing day care costs can make a lot of difference.
  • Partnering with patient advocacy groups and establishing patient alumni networks and patient communities to obtain deeper insights and greater engagement
  • Establish increased transparency by sharing aggregate trial results
  • Developing patient-friendly websites
  • Creating a digital health strategy to listen to the patients’ voice
  • Conducting virtual clinical trials – enhancing access to clinical trials. Providing the patient with the comfort of participating from home
  • Empathy is a very big piece of this. AI driven customised text-messaging, that can respond to patient’s needs.

While many companies are implementing novel ‘patient-centric’ strategies, there is still some ambiguity in defining the right measures of success to determine the efficacy of the implementation strategy. In a survey conducted by Deloitte across pharma, medtech and patient advocacy / disease research organisations, it was found that challenges still exist in establishing the performance of a ‘patientcentric’ model (Myers et al, 2020).

Some short-term Return on Investment (RoI) metrics that are used to measure the success of a patient centric approach include:

  • Higher patient satisfaction scores
  • Improved recruitment and retention
  • Faster Trials
  • Fewer protocol amendments
  • Greater brand loyalty.

The viewing lens is changing – the patient is finally finding a voice – the patient perspective is actually being obtained from the patient – not from the provider or payer, nor from the regulator or the sponsor. The consumerisation of care and higher levels of patient education has encouraged the development of a patient-centric approach (Robinson, 2014). A very interesting difference in patient vs physician perspective has been shared by John Bridges, a professor at Johns Hopkins University, who brought to light striking differences between the patient’s and the physician’s perspective. He highlighted that in patients with schizophrenia, patients prioritise improved satisfaction, independence, physical health, activities of daily living, and work capacity, as against decreased psychotic symptoms, improved self-confidence, improved capacity for communication and emotion, and decreased mistrust and hostility, which were prioritised by physicians (Myers et al, 2020).

The FDA has been a catalyst of change driving Patient-Focused Drug Development (PFDD) and is developing 4 guidances on how sponsors can obtain comprehensive patient input, how they can identify what is important to patients, the methods for developing fitfor-purpose clinical outcome assessments (COAs) and how these COAs can be incorporated into regulatory decision making (FDA, June 2020). The main objective of PFDD is to assess how to better incorporate the patient’s voice in drug development and evaluation. The FDA has organised several patient listening sessions in collaboration with NORD (The National Organization for Rare Disorders), which have been helpful in obtaining the patients perspectives, both in terms of the impact of the treatment on a day-today basis, as well as the long-term impact. There are also FDA led and externally led PFDD meetings and the FDA’s Patient Representative Program (PRP), in which Patient Representatives provide direct input to inform the Agency's decisionmaking (FDA, August, 2019).The Patient Engagement Collaborative (PEC), a joint initiative of CTTI (The Clinical Trial Transformation Initiative) and the FDA involves meetings of the FDA with 16 diverse representatives from the patient to achieve more meaningful patient engagement in drug development and regulatory decision making (December 2018).

In a survey conducted by CTTI in 2017 on 193 patients in the US across four therapeutic areas, that 90 per cent were willing to use alternate modes of communication with a trial doctor instead of in-person visits and 76 per cent indicated that they would prefer to participate in a mobile trial instead of a traditional trial and thought that the data would be more accurate. Many were also very willing to use mobile apps, wearables devices and patches, bodilyfluid diagnostic devices, and ingestible sensors (Perry et al, 2019). Thus, technology is not only being increasingly accepted by patients, but is becoming a way of life for them.

In a survey conducted by CTTI in 2017 on 193 patients in the US across four therapeutic areas, that 90 per cent were willing to use alternate modes of communication with a trial doctor instead of in-person visits and 76 per cent indicated that they would prefer to participate in a mobile trial instead of a traditional trial and thought that the data would be more accurate. Many were also very willing to use mobile apps, wearables devices and patches, bodilyfluid diagnostic devices, and ingestible sensors (Perry et al, 2019). Thus, technology is not only being increasingly accepted by patients, but is becoming a way of life for them. Digital Health Innovation (May 2020). The FDA recently approved a video game called EndeavorRx, developed by Akili Interactive Labs to treat ADHD. This has become the first video game to be approved by the FDA as a digital therapeutic (Nield, 2020).

Yet patient’s still want the personal touch and don’t want to participate in a trial in a vacuum (Stoecker, 2019). To make it even more personal is Mabu, Catalia Health’s AI enabled robot which helps treat patient’s with chronic illnesses. It uses AI to learn about each patient through daily conversations, provides feedback to the patient and shares data with the healthcare provider as well (Winn, 2019).

Laura Holmes Haddad, cancer survivor, who shared her journey at the DIA Annual Conference 2020, highlighted three things that drive patient centricity:

  • Acknowledging the patient behind the number
  • Easing the economic burden on patients
  • Educating the provider.

She emphasised that though the trial sponsor and the patient are inextricably linked, at the nucleus of this relationship, humanity is the core.It’s really simple isn’t it – keeping the patient in the centre – or is it? There has been a paradigm shift. The focus has shifted from the healthcare practitioner to the patient. Patients are indeed uniquely positioned to inform drug development. We need to understand their language, to hear what they are saying – and be sensitive to their needs. To quote Dr. Eric Topol, ‘The Patient Will See You Now!’ The world today is truly becoming ‘patient-centric’.

--Issue 40--

Author Bio

Nimita Limaye

Nimita Limaye has over two decades of life sciences leadership experience and serves as the SVP, Strategic Partnerships & Medical Writing at CSOFT Health Sciences. She is a strategic business leader with a strong understanding of the drug development industry, with rich cross-cultural experience working across the US, Europe and Asia.

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