By Kai Langel
The pharmaceutical industry is reinventing itself to be more patient-centric rather than product-centric, which is great news. However, many would claim that this transformation is taking place at a frustratingly slow pace and that there is a lot of talk about patient engagement and centricity, but far too little action.
To discover how members of the industry define patient engagement in the first place, eClinicalHealth interviewed more than 50 individuals from various backgrounds, including regulatory, clinical operations, technology and patient advocacy, asking them one simple question: “What does patient engagement mean to you?” We expected responses to fit into a few well-defined categories like “engaging patients to promote a clinical trial opportunity” or “engaging patients during the trial conduct” or “engaging with patients who use our products.”
To our surprise, however, the responses were more varied and often depended on the respondent’s role. One of the most insightful responses was from a person working with patient advocates. He said that patient engagement should mean that patients have a hand in all these tasks:
- Defining patient needs relating to a disease
- Designing the products and services to address their needs
- Supporting the trial programs to develop said products
- Providing feedback on how well these products addressed their needs in the end
This observation carries an important message to all of us in the industry, encouraging us to broaden our perspectives to continue our work with the patients in mind. By meaningfully engaging patients in our clinical research, we all stand to benefit.
Case Study Overview
eClinicalHealth, a cloud-based eClinical technology company, led a trial in Finland with partners Sanofi, Langland and Mendor utilizing a single wireless blood glucose meter in a completely remote clinical trial setting. The objective of VERKKO, this Phase IV clinical trial for diabetes, was to evaluate the use of eClinicalHealth’s patient-centric Clinpal platform integrated with Mendor’s 3G-enabled wireless blood glucose meter and assess the performance of the novel remote research model.
In this case study, we will examine the VERKKO clinical trial with particular attention on patient recruitment and engagement. We will share best practices and lessons learned by elaborating on the actions that can be taken before, during and after trials to improve patient engagement and, ultimately, trial execution and operational success.
Engaging Patients Prior to Trial Start
One of our takeaways from our remote VERKKO trial is the importance of proactively seeking patient input during trial design, prior to launch.
In our trial, we captured patient feedback at the end of the trial — which we will describe in more detail later. Both the quantitative feedback and the comments were overwhelmingly positive. However, what got our attention was the patients’ willingness to share their thoughts far beyond what we asked. For example, when we asked about their satisfaction with the automated glucose profiling mechanism, patients reported very positive satisfaction ratings, but added that they would have liked the ability to record insulin use and carbohydrate intake. They also pointed out some parts of the instructions that were not as clear as they could have been. Had we known this from the start, this would have been very easy for us to address.
So, how do we as an industry get that patient input before the trial begins?
Patient focus groups are one option, enabling in-depth engagement with a limited number of individuals. But in this trial, we used our patient engagement system Clinpal, which enabled us to engage a patient community in an automated manner, allowing patients to view a video about the planned trial or program and then provide feedback via a numeric rating or open-ended comments. Obtaining this kind of communication early can be invaluable. As this is not a trial-specific activity, it can be launched efficiently without the need for IRB or ethics committee approval.
Online Recruitment: Easy for Investigators and Simple for Patients
In the VERKKO trial, we recruited patients through targeted ads on Facebook, directing patients to learn about the trial online and complete a prescreening questionnaire, after which they received their login credentials to Clinpal. During the trial enrollment phase, candidates were invited to log in to access their personal dashboard and see the status of their application. They also had access to additional patient-facing trial documents. If they had any questions, they could reach out to the trial site using secure messaging.
We recruited 74 patients entirely through Facebook. Sixty of the 74 registrations were enrolled in the trial, representing an 81% conversion rate.
Our technology platform enabled us to ease both administration and patient concerns. For example, once the site had reviewed and accepted their application, patients could access the electronic patient information sheet to learn about the automated blood glucose measurement process they would use and other key trial aspects. After completing a short quiz to confirm their understanding, patients were invited to electronically sign the consent form, indicating their approval to join the trial and confirming their questions had been answered. All this was completed remotely.
Another important outcome of online recruiting is the level of technology acceptance, even in an older generation. The average age of patients who completed this trial was 56 years old and several participants were 70 years and older. All age groups reported a consistently positive experience throughout the conduct of the trial.
Patient Engagement and Retention
Capturing patient feedback and satisfaction ratings in the VERKKO trial was insightful. We were pleased satisfaction was very high: Overall patient satisfaction related to their trial participation was rated as 4.52 out of 5.
But what if things hadn’t gone so well? Especially in a remote trial, we would have had no idea that participants were dissatisfied because we never saw them. Perhaps we would have seen poor compliance or a high drop-out rate, but we would not have had any insights about why this is. This can be an issue in site-based trials as well, as visits are often infrequent and patients may hesitate to share concerns in front of the site staff.
The average drop-out rate across all clinical trials is around 30%, but patient retention is a problem that sponsors are often either not aware of or don’t proactively address. Over-recruiting is often the fix; however, it’s an expensive way to address it. An even larger issue may be missing data that candidate dropouts create, which causes noise in the data due to the conservative statistical methods to “fill” the missing data with default values. In the end, if you have too many dropouts, it may be impossible to demonstrate clinically meaningful efficacy due to this issue.
The fact is that sponsors should think very hard about how to keep every single individual in the trial they have recruited. This requires proactive planning with early-stage patient engagement, requiring sponsors to have insights about how their patients are doing and what concerns they may have.
Measuring patient satisfaction is best done by engaging patients throughout the trial. The Clinpal platform further allowed us to survey patients online who did not get enrolled about their experience, while patients who were enrolled could be queried about their views about the upcoming trial — allowing researchers to address any concerns up front. For example, a difference in participant satisfaction with the same trial in different countries may point to training issues at the country level. Perhaps sites where patient satisfaction is higher than average are using some best practices that can be applied elsewhere to increase overall satisfaction.
After patients were accepted into our VERKKO trial, the study materials — including the single, connected device for blood glucose measurements — were delivered directly to patients along with instructions for registering the device with their online Clinpal account to capture their structured blood glucose profiling routine.
Throughout the trial, patients had access to their personal dashboard, which included a visual study guide, so they could see activities they had already completed and upcoming milestones. They also had access to their blood glucose data, enabling them to see their measurements and compare them to their personal daily routines set earlier on in the process.
Patient measurements were instantly and automatically transferred to the Clinpal system where a logbook view and compliance dashboards were available to trial personnel for remote management. This is important not just for the sake of the data but also to ensure patient engagement as visibility into the research process can be important for participants, especially in a remote trial setting. Clinical trial sponsors should review and assess their protocol and engagement strategy, watching for any long periods with no site visits or for events within a trial where patients may require extra motivation.
At the end of our VERKKO trial, patients also had access to the full profiling report, which showed their average blood glucose excursion for the three daily routines, providing them insights into their diabetes control. It was clear from the comments that patients appreciated having this information available.
Comparing Patient Response in VERKKO Trial to Comparator Trial
The VERKKO trial was conducted with a “sister protocol” in which a second trial was conducted with an identical profiling mechanism but in a traditional manner with in-person visits and training at the trial site. This allowed us to compare some metrics directly. One significant finding was that in the VERKKO trial, patient compliance improved 18% compared to the traditionally conducted trial. The protocol was far from simple, requiring measurements within strict time windows; patients had to fully understand the protocol in order to be compliant. The fact that they did this so well on their own is a likely indicator of an efficient and patient-friendly informed consent process.
- Patient recruitment, conducted fully online was completed 56% faster compared to the previous trial, which recruited participants through eight participating trial sites.
- Fifty-one patients received their Mendor Smart meters and started the profiling protocol, with 46 completing the profiling process, a 9% drop-out rate, which was the same as in the comparator trial.
- Patients completed the glucose profiling 22% faster compared to the previous trial, resulting in shorter overall trial duration as well as a smaller time commitment for each patient.
- The trial site estimated having spent 66% less time in trial coordination activities. The entire trial was mainly managed between a single investigator and nurse, who were physically located in different areas.
Lessons Learned from Trial Exit Interviews
Patients taking part in trials are already sharing a lot of information with the sponsor and are generally willing to provide feedback. In the VERKKO trial, we had a 100% response rate to our online exit interview survey, which was part of the automated workflow in Clinpal. We measured several aspects, including importance and patient satisfaction. We also asked patients how much time they spent overall. The numeric ratings were useful, but they mostly confirmed that the trial was highly efficient and that most patients enjoyed being part of it.
The written comments, most of which were very positive, were particularly valuable as were the patient recommendations. For example, many patients did not like that we did not provide envelopes and stamps to return the study materials, so patients had to pay for this out of pocket. Patients commented on the volume of the alarms in their wireless glucose meters and wanted more flexibility with the time windows for their measurements. Several pointed out things that could have been more clear in the instructions. They also asked if the meter could have a counter showing the time until the next measurement.
The many comments we received will be truly helpful to us in the next trial. Our lesson learned is the value a pilot would offer. By first obtaining feedback in a small-scale pilot, we can then incorporate that feedback into a full-scale trial.
The VERKKO trial design mirrored the way the general public prefers to exchange information by providing education and opportunities to communicate online. Increasingly, people worldwide are using the internet to gather information and to communicate. Sixty-four percent of U.S. consumers are willing to see a doctor via video visits, and 70% say they would rather obtain prescriptions from their doctors via an online video visit rather than an in-office visit. Trends like these open opportunities for the clinical research industry, as this trial demonstrated.
The approach used in VERKKO is ideal especially for observatory studies that often involve large patient populations and require a more efficient approach. However, online patient recruitment and engagement can benefit studies of any phase.
All these benefits address critical challenges in clinical trials, translating into direct business value and increasing the return on investment. Perhaps, more importantly, when we provide patients with an efficient and convenient way to participate in trials, we have more engaged and better-informed patients, driving us toward better science.
Kai Langel, Co-Founder and Director, Patient Solutions, eClinicalHealth