Clinical Researcher—February 2022 (Volume 36, Issue 1)

PRESCRIPTIONS FOR BUSINESS

Jaydev Thakkar, MBA

 

The concept of “patient-centered care,” loosely defined as situations in which clinical decisions are based on the needs, goals, and preferences of the patient—not the physician—is decades old and broadly accepted among most healthcare providers. Patient-centered care is believed to encourage patient engagement by involving the patient in more care decisions and collaboratively helping him or her overcome obstacles that could interfere with an optimal outcome.

Patient-centeredness, however, is only now—in part thanks to the COVID-19 pandemic—reaching a tipping point in clinical research. Although flexibility and excellent care are expected, historically, clinical trials and other types of research were driven by the needs of site-centered research, which could require extensive travel and time lost for study participants. The pandemic initially brought travel and many types of elective healthcare procedures to a halt, and likewise, clinical trials. New participant enrollment in April 2020, for example, was down 79% compared to the previous year.{1}

Research to develop new therapies that could improve outcomes and quality of life—and even save lives—needed to continue despite patient reluctance to participate. Enter decentralized clinical trials (DCTs). Although not a new concept, DCTs have accelerated in recent years{2} due to the expanded capabilities of wearable sensors and other monitoring devices that can be easily, or even passively, operated in the patient’s home.

More importantly, though, many patients prefer DCTs because the practice allows them to stay in the comfort of their home for most of the trial. On the other hand, while patient-centeredness can be advantageous for recruitment and retention, a DCT could end up posing greater challenges for life sciences companies and contract research organizations (CROs). Deciding what type of research to conduct virtually is important, for example, as is the technology used to gather and analyze data. Leading companies are even developing digital therapeutics along with pharmacotherapy to be co-prescribed for maximum efficacy.

When the optimal strategy is chosen, however, DCTs and hybrid models that include remote and in-person elements can result in significant cost savings and can accelerate timelines for clinical researchers. Essential to this outcome is to stay focused on the patient in all aspects of trial design and execution.

Why DCTs?

As of late 2020, more than three out of four (76%) life science organizations report at least some of their trials have already been decentralized, and 38% indicate more than half are decentralized.{3} Other than COVID-19, one of the reasons for this shift is nearly 70% of potential clinical trial participants live more than two hours away from a study center.{4}

Similarly, survey results from 2017 show that nearly one-quarter (23%) of participants in a clinical research study reported that the location of the study was what they liked “least” about the research, which was a close second to “possibility of receiving the placebo” (24%) as their top concern.{5} More than 1 in 10 participants (11%) said site visits were too time-consuming. Other survey results of patients with chronic conditions found “inconvenience of travel” as one of the most common reasons for non-participation.{6} These obstacles to participation and retention for an onsite research study can be worsened by the frequency of visits, patients’ out-of-pocket costs, and patient frailty.

Meanwhile, patient comfort with telehealth and remote patient monitoring is high. A 2020 survey of patients found 98% of patients reported satisfaction with telehealth.{7} Likewise, 74% of patients with COVID-19 reported satisfaction with a remote patient monitoring program that included around-the-clock tracking of their vital signs.{8} An even earlier survey of post-lung transplant patients found that 90% of participants were satisfied with a home spirometer program that included electronic transmission of data as well as assessment and management by remote clinicians.{9}

DCT Use Case Example: Heart Failure

DCT or hybrid models can engender high satisfaction levels by eliminating logistical challenges for patients. In addition, these models are applicable for a wide range of therapeutic areas, such as heart failure, where timely initiation and dose intensifications of guideline-directed medication therapy (GDMT) continue to be a major challenge despite the availability of guidelines from professional societies, such as the American Heart Association and the American College of Cardiology. Less than 1% of heart failure patients are on the optimal dose of their heart failure medication and less than 25% of eligible patients receive all of their GDMT medications.{10}

Clinical decisions regarding the use and dosing of GDMT among heart failure patients must take into consideration various factors, including medical history, vital signs, laboratory data, and patient symptoms, as well as medication-related side effects. Currently, medication decisions are made by the care team periodically during in-person or virtual clinical interactions based on data gathered from disparate data sources.

Digital Therapeutics and DCTs

Decentralized and hybrid trials and research are now under way to study more efficient ways to identify optimal medication and dosage using digital therapeutics. By combining wearable sensors, an artificial intelligence algorithm based on real-world data and patient-facing tools, digital therapeutics can help investigators more quickly achieve optimal therapy because they help clinicians more accurately assess a patient’s health status and drug tolerance through continuous physiology monitoring and inclusion of lab assessment results for analysis.

Digital therapeutics, which are typically categorized as software-as-a-medical device (SaMD), also improve engagement and retention by automatically prompting clinicians and patients for medication initiation and up-titration while the burden of site visits is eliminated through a patient-clinician communication system that can include streaming video encounters through a mobile device. Lastly, using a SaMD to support DCTs requires fewer resources than nurse-led programs because safety management and titration recommendation management guidelines can be distilled in the system.

Not only are such digital therapeutics being used to study drugs, but leading pharmaceutical companies are developing solutions that incorporate a SaMD to be co-prescribed as a companion to the drug to help determine efficacy and tolerance sooner and develop personalized treatment options. Likewise, the technology also enhances clinical research as a care option by flagging early deterioration in a patient’s condition well before a medical crisis would have otherwise occurred. This tap on the clinician’s shoulder enables him or her to intervene early to avoid costly and devastating medical issues and to improve outcomes overall—all while advancing clinical research.

Avoiding the Technology Burden

While site visits and travel can be a burden for patients, so can the care-at-home technology used during decentralized and hybrid clinical trials. If the technology is too complicated, or trial demands are too onerous for patients at their homes, engagement and retention can suffer despite patients’ growing acceptance of telehealth and home health devices. Some technology factors clinical researchers should consider include:

• Patient burden. How much data entry will be required of the participant? If there are too many daily or weekly forms to fill out, too much testing to perform, or complex software to navigate, then investigators can expect more dropouts, or even worse, inaccurate or unreliable data. The technology platform should offer a simple user interface while automatically collecting as much physiologic data as possible, alleviating the patient from conducting their vital signs testing and reporting. The research should not require the patient to repeatedly fill out long, complicated forms, but rather questionnaires that take only a few minutes to complete.
• Clinician burden. Emerging technologies inevitably prompt the need for education and support for patient questions or technical troubleshooting. Also, site staff can be overwhelmed by inventory management and logistics. Investigators and site staff, however, should be focused on patient care, reviewing actionable alerts, and promoting patient engagement with excellent care, not technology issues. Life science companies and CROs should select a technology partner that will support the complete platform with helpful, knowledgeable patient-facing representatives to troubleshoot and resolve challenges. Also, ensure that a technology partner can handle logistics and inventory management of devices, shipping direct to patients’ home when needed, remotely onboarding patients on the technology platform, and tracking patient compliance.
• Device agnostic. The platform selected should also not limit investigators to what type of device they can use to drive their research. A device-agnostic, fully integrated remote patient monitoring platform also limits the number of vendors that researchers must manage and makes trial participation more seamless for patients.
• Modular and scalable. Few life science firms or CROs study just one therapeutic area. By choosing a highly modular and scalable digital therapeutic platform to support research, investigators can pursue DCTs and hybrid studies across a wider range of conditions and easily expand the number of participants as needed.

Beyond Trial Support

DCTs can be leveraged to investigate drugs as well as digital therapies. For example, a rather remarkable study found patients receiving chemotherapy for metastatic solid tumors survived longer when they used a web-based tool to document their symptoms compared to those who did not.{11} Instead of talking with a nurse or physician by phone or a site visit, a randomly selected group of patients answered a simple weekly questionnaire online about the side effects of chemotherapy. Researchers determined that health-related quality of life improved for the intervention group, the members of which also survived for a median five months longer than those in the control group, which is an outcome that some oncology drugs would hope to deliver.

Researchers did not conclude that reducing site visits or travel influenced this outcome, but the study and others demonstrate the possibilities of clinical research and therapeutic solutions that enable patients to remain in the home more often. With a focus on patient-centeredness and using technology solutions that alleviate participant burden, life sciences companies and CROs can not only improve their recruitment and retention, but also arrive at meaningful results sooner using fewer resources and driving optimal outcomes.

References

1. Sathian B, Asim M, Banerjee I, et al. 2020. Impact of COVID-19 on clinical trials and clinical research: A systematic review. Nepal J Epidemiol 10(3):878–87. doi:10.3126/nje.v10i3.31622
2. Chancellor D. 2020. Decentralized and Hybrid Trials 2020: Global Research Study into Adoption and Technologies. Clinical Trials Europe Conference presentation. https://pharmaintelligence.informa.com/resources/product-content/sitecore/shell/~/media/informa-shop-window/pharma/2020/covid-24-campaign/slides/decentralized-clinical-trials-in-2020.pdf
3. 2020. Survey: COVID-19 the Tipping Point for Decentralized Clinical Trials. https://www.oracle.com/news/announcement/covid-19-the-tipping-point-decentralized-clinical-trials-111820.html
4. 2017. Sanofi’s Digital Initiative Simplifies Patient Participation in Clinical Trials. https://www.sanofi.com/en/science-and-innovation/patient-participation-in-clinical-trials
5. Anderson A, Baker H. 2019. Building Patient-Centric Trials Putting the Patient First. CISCRP and Medical Research Network presentation. https://www.ciscrp.org/wp-content/uploads/2019/08/CISCRP.MRN-Slide-Deck-7.17.pdf
6. DasMahapatra P, Raja P, Gilbert J, et al. 2017. Clinical trials from the patient perspective: survey in an online patient community. BMC Health Services Research 17 (article 166). https://doi.org/10.1186/s12913-017-2090-x
7. https://www.mckinsey.com/industries/healthcare-systems-and-services/our-insights/helping-us-healthcare-stakeholders-understand-the-human-side-of-the-covid-19-crisis
8. Kodama R, Arora S, Anand S, Choudhary A, Weingarten J, Francesco N, Chiricolo G, Silber S, Mehta PH. Telemedicine and e-Health (ahead of print). http://doi.org/10.1089/tmj.2020.0459
9. Finkelstein SM, MacMahon K, Lindgren BR, et al. 2012. Development of a remote monitoring satisfaction survey and its use in a clinical trial with lung transplant recipients. J Telemed Telecare 18(1):42–6. doi:10.1258/jtt.2011.110413
10. Greene SJ, Butler J, Albert NM, DeVore AD, Sharma PP, Duffy CI, Hill CL, McCague K, Mi X, Patterson JH, Spertus JA, Thomas L, Williams FB, Hernandez AF, Fonarow GC. 2018. Medical Therapy for Heart Failure with Reduced Ejection Fraction: The CHAMP-HF Registry. J Am Coll Cardiol 72(4):351–66. doi:10.1016/j.jacc.2018.04.070; PMID:30025570
11. Basch E, et al. 2016. Symptom Monitoring with Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial. Journal of Clinical Oncology 34(6):557–65. doi:10.1200/JCO.2015.63.0830

Jaydev Thakkar, MBA, is Chief Operating Officer of Biofourmis, a digital therapeutics, decentralized clinical trial, and virtual care start-up based in Boston, Mass.