Anna Skabeev

Clinical trials often serve as the first point of interaction between a patient and a sponsor company. Nevertheless, clinical teams can lose sight of this fact when designing the technical components of clinical studies. The outcome can be cumbersome trial protocols adding unnecessary burden on patients already in a challenging situation, and, therefore, unhappy patients, low recruitment and high dropout rates, as well as low scores on company perception surveys.

	The intent of patient-centric clinical trials is to lessen the burden of participation by making the participant journey as convenient and pleasant as possible, and, therefore, help in addressing the issues above.

	While terms such as “patient centricity” and “patient-centric trials” have become industry buzzwords and made their way into various publications and oral presentations, there is still much to do when it comes to implementation. The aim of this article is to provide practical overview on what clinical trial managers (CTM) can consider in their work to take a step toward patient-centric trials today using the current clinical trial model. 

	In a theoretical example, a CTM is accountable for a high-profile trial within a new therapeutic area for their organization. The company’s 2017 corporate goal is continuously on display throughout the office: “all staff are to implement goals and measures related to patient’s satisfaction and loyalty.” By measuring patient satisfaction across the organization, executive leadership anticipates the establishment of a baseline understanding of how the company is perceived by its most important stakeholder, the patient.

	It is easier said than done: the only patient satisfaction data you have, in this example, is from an orphan drug Phase III trial a year ago, in which retention rates were disappointingly low. Participants complained of challenging visit schedules and poor communication of the trial intent, design, and outcomes. Consequently, the study was delayed and over budget. Most companies have looked only at cost, timelines, and quality of results, not patient or site experience. But patient and site experience plays an important role in all of these factors. You want to execute a successful trial by implementing a more patient-centric approach. How can you make the clinical trial journey more efficient and less cumbersome for the participants and clinical staff? 

	Figure 1 below illustrates gaps in the trial continuum from a participant perspective. By adequately addressing the gaps at every phase of the process, a CTM can help ensure that their trials are designed in a way that is not just scientifically rigorous, but also incorporates patient perspectives.

	Improvements in patient-centricity can be made throughout drug development and life cycle management, from trial planning activities to product launch. Trial planning activities may include live protocol simulations, patient advisory boards and other ways of soliciting patients and caregiver input on what a trial should include, and protocol review committees with key cross-functional stakeholders outside the organization (including patients and patient advocacy organizations). Some companies use crowdsourcing at the protocol development stage to gain patient insights on the protocol, including endpoints and procedures. By thorough planning that prioritizes the participants’ trial experience, CTMs can help ensure that they are considered stakeholders in the trial experience and results. 

	The quality, timelines, and, therefore, the cost of a trial is significantly affected by the commitment of the participants to achieving a successful trial. This commitment increases with a deeper understanding of trial requirements, and, thus, willingness to follow all trial routines, such as regular attendance of trial visits, timely and detailed reporting in patient diaries, and the quality of patient-reported outcomes. Although the FDA has not developed specific guidance on all possible aspects of patient-centric trials, the agency does emphasize the importance of incorporating patient perspective in the development and evaluation of new medicines and has several 

	Incorporating the patient perspective into trial planning and activities is not an easy task that can be done by the CTM alone. However, unless an organization has a function dedicated to patient-centricity, the CTM will need to be the driver and ensure that the appropriate internal and external stakeholders are at the table. The person may also need to assist in the development of guidance and policies for his or her organization, particularly regarding compliance and the selection of third-party vendors. Success depends on the support of multiple groups in the organization, including legal and compliance, regulatory, corporate communications, medical research, and medical affairs. Outside the company, buy-in from external patient advocacy groups and clinical trial sites will be needed to complement the company’s support. If a CTM runs their study with a contract research organization (CRO), it, of course, will need to be involved from the get-go. 

	For maximum impact, the CTM can do the following:

		Review patient-centric approaches used by other companies in the same therapeutic area: what can you earn from current practice and outcomes? 

		Mindfully assess eligibility criteria to ensure they are not too restrictive 

		Mitigate unnecessarily complex protocols by involving the patient in the design process 

		Start the clinical trial planning process early, ideally 10 months prior to trial launch, to ensure time for refining and implementing the patient-centric approach 

		Build in additional time and budget for training of site staff

		Track the changes that incorporating a more patient-centric approach makes to timelines and budget

		Collect evidence to make the business case for patient-centric measures to your supervisors: enrollment and dropout rates, budgets, timelines

		Above all, consider the clinical trial patients’ journeys-how patients are making their decisions about trial participation-throughout the planning process  

	During the planning process, cultural differences should be considered. In the era of global clinical development, patient communication and trial materials must be created with cultural differences in mind and available in multiple languages. Better results at local sites will be achieved if staff are empowered to put necessary customizations in place. Patient registries can also help sponsor companies improve the post-trial relationship with participants. The role of a global CTM is to work with local colleagues to ensure these nuances are considered throughout the clinical trial phases. 

	Throughout trial start-up, recruitment, and retention, thoughtful communication with participants is essential to the establishment of patient-centric practice. Before the trial even begins, companies should publicize the trial appropriately, through government websites, patient advocacy and treatment center websites, and, as appropriate, mass advertisement.

	Make your sites partners in the trial by soliciting their input and providing training and materials before recruitment begins. Their role is critical; they can make the journey for the patient less complicated and more rewarding. From the start, remind your sites to convey the concrete benefit to a participant in culturally-appropriate ways: that he or she is often getting even more attention and oversight of their care while they are in a clinical trial, even if they receive the placebo. Schedule regular patient experience evaluations in addition to standard clinical assessments. The CTM can help ensure that the sites (with the support of the sponsor) can provide input on local culture and have the materials they need to include participants as active partners in advancing critically important research. Acting mindfully, a CTM has a chance to help sites make participants true partners in the trial process.

	Above all, emphasize that two-way communication between site and participant is the priority. This principle should inform the “toolkit” a CTM provides to their sites so that they can do the following effectively: 

		Get participant feedback before executing by asking questions about scheduling, etc.: “Will this be onerous for you?” Sites need to look several steps ahead to allow for patient schedules (work/family)

		Set participant expectations: these are the responsibilities and rights as a participant. Always offer to include the participant’s caregiver (if any) 

		Discuss and explain protocol endpoints and other scientific aspects of the trial with participants before, during, and after the trial 

		Explain expected protocol operational hurdles and opportunities to participants; solicit their advice on addressing these issues

		Ensure that the sites have easy means of providing feedback throughout the trial. Timely feedback can help the CTM and sites address unforeseen problems that arise before the trial is negatively impacted

		Explain that it is the participant’s responsibility to keep the study blind. They are essential members of the team 

		Cultivate patient loyalty: anticipate their questions and objections and have answers ready in lay language

	Once the trial is underway, similar strategies and tools can improve patient retention. In addition to providing standard appointment reminders, CTMs can use e-diaries, wearable devices, and even “bring your own devices” (BYOD) to make participation easy, collaborative, and interactive.

	BYOD allows participants to use their own devices, like smartphones and tablets, to complete study assessments, such as monitoring daily activity and collecting patient reported outcomes (PRO) and quality of life data. The BYOD devices approach may also be used to enhance communication with study participants through easy and virtually no-cost measures, such as sending out study visit reminders or sharing individual trial data.

	BYOD has recently been evaluated, by Bracket, in a Phase II Parkinson’s disease clinical trial. Results were presented at the Annual DIA Meeting in June 2016. Participants used an application that included a mix of surveys and tasks. The active phone sensor collected and tracked their progress. Over the course of the study, adoption went up and, by the end of the trial, 80% of the data was submitted via the app. Adam Butler, Bracket’s Senior Vice President for Strategic Development, expects to see a “tipping point of very heavy adoption” of BYOD in clinical trials over the next three to five years.

	Participants that feel involved in the process through these strategies may even offer more and better feedback. With sufficient funding and staffing for the sites, CTMs can go even further by incorporating home visits by site staff and/or healthcare professionals. Including these strategies in trial design can help CTMs create and manage patient-centric programs that can lessen the burdens on the participants and improve results. 

	Once participants are chosen, communication toolkits for the sites can help staff establish a more personal relationship between patients and the company through basic low-cost components such as a welcome letter and information about the trial in lay language. Other ways in which the CTM can improve the participants’ experience include the following: 

		Engagement and community building, via patient associations, face-to-face advisory boards via third parties, surveys, social listening, and other channels

				Participant newsletters and brochures written in lay language

				Talking points for the sites to supplement these materials

	As simple and inexpensive as these measures are to execute, surprisingly, most companies do not provide them to participants consistently. CTMs can step up and fill this gap to begin establishing a patient-centric experience for participants from the first interaction.  

	Carrying the patient-centric principle through the post-trial period is critical. CTMs can play a role managing this process. For example, a simple “thank you” for trial participation can go a long way and help a patient consider participation in a future study. Sharing trial results in a lay language improves the company-participant relationship. It is also the right thing to do from an ethical point of view. Still, most patients do not receive information regarding the outcome of the trial they participated in or of the important role that they played.

	Patient-centricity may lie beyond the scope of a typical development program. Collecting real-world, long-term data is critical and can be achieved via patient registries. While the idea sounds simple and not new, there are still a lot of questions when it comes to how. The Clinical Trial Transformation Initiative (CTTI) has a work-stream underway to develop recommendations with the aim to increase use of patient registries in clinical research.

	The main intent of assessing these measures is to understand the percentage of participants touched by patient-centric tactics. This will guide CTMs for upcoming trials by identifying what innovations work best. A CTM can also, at the end of a trial, ask for direct feedback from participants, via a third party, on the patient-centric activities that were implemented. Keep in mind that you might see cultural and regional differences for which you should account in reviewing results. The following participant information from the sites can help a CTM understand results, refine techniques for future trials, and report learnings to   colleagues: 

		Percentage provided insights on protocol, endpoints, and operational hurdles to overcome 

		Percentage educated about the general trial journey and the one they are to consider joining

		Percentage informed about trial progress 

		Percentage that were part of a trial community 

		Percentage that received a thank you from the sponsor via the site 

		Percentage that received lay language summary reports of trial outcome via the sites 

		Follow-up by sites, with a CTM’s guidance, can include the following:

		Identifying areas in which participants need further education on the clinical trial journey in general and for the protocol specifically

		Conducting participant surveys during and after the clinical trial

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