PDTs Represent a Shift in How Treatment Is Delivered

Prescription digital therapeutics (PDTs) are part of a broader category of digital health products that may be used for lifestyle, wellness and other health-related purposes. However, the difference is that PDTs require clinical evidence and regulatory oversight, as well as a prescription from a healthcare provider, explained Mahsa Salsabili, Pharm.D., Ph.D., in a Managed Healthcare Executive K-Cast video series. Salsabili is lead pharmacoeconomist at UMass Chan Medical School in Worcester, Massachusetts.

PDTs use software to prevent, manage and treat medical disorders and diseases based on clinical evidence and validated behavioral therapeutic principles. There are already more than a dozen of them on the market in the U.S., with more under development. To be authorized for use on the market, they undergo clinical studies to demonstrate their safety and efficacy.

“[PDTs] are legally permitted to make claims about treating specific conditions and must comply with regulations for manufacturing, quality control, postmarket surveillance and so on,” Salsabili said. “These are key components that differentiate [PDTs] from the general health and wellness apps, which don’t undergo the same clinical testing or regulatory oversight.”

Approval process

The approval process for PDTs to be a therapeutic software product involves several steps, starting with a presubmission stage where the designation is discussed with FDA officials to determine the appropriate regulatory pathway. This stage also provides information to the company on the clinical study requirements and evidence needed.

The actual submission includes evidence on the product description, validation and clinical data. There is also software documentation covering the design, risk control and cybersecurity. The FDA assesses the software’s performance, usability and security controls with human testing, evaluating potential use risk and the possibility of errors.

Once the PDT is approved, the manufacturer will create periodic safety reports and submit real-world use data. They may also be required to gather evidence in postapproval studies.

“Although digital therapeutics are categorized as medical devices, they have research and development requirements similar to pharmaceuticals in that clinical studies are required during the premarket approval process to demonstrate effectiveness and safety for a specific therapeutic indication,” Salsabili said. “However, unlike the extensive preclinical and clinical trial requirements specified for drug manufacturers seeking a new drug approval, the FDA has limited guidance regarding the evidence standards necessary for approval of digital therapeutics products.”

Disease use

PDTs have a significant focus on conditions that have a behavioral component to them that might benefit from a product using cognitive behavioral therapy (CBT). PDTs have use in mental health conditions and chronic diseases.

For depression, anxiety, attention-deficit/hyperactivity disorder and posttraumatic stress disorder, PDTs deliver CBT and mindfulness therapies. For substance use disorder (SUD), PDTs use contingency management and therapeutic education. In chronic diseases, PDTs use medication and lifestyle coaching in diabetes, obesity and cardiovascular disease; symptom tracking and adherence support for respiratory conditions; and CBT and mindfulness therapy for pain management.

With or without standard treatment

Typically, PDTs are used as a stand-alone therapy for mild to moderate cases and early-stage or well-controlled disease. However, they can also be used alongside traditional treatments or other therapy for severe illness. For chronic pain management, PDTs might be used with physical therapy and pain medications. For patients recovering from SUD, PDTs might be used in conjunction with counseling and medication-assisted treatment.

Although PDTs might not be suitable for severe, high-risk or complex cases as a monotherapy, Salsabili said, it may be used as a monotherapy as a prevention before disease progression. “Using [PDTs] as a monotherapy offers several benefits, including increased access to treatment without requiring in-person provider visits, potentially lowering costs as a cost-effective frontline treatment and catering to patients who prefer an app-based, self-guided approach,” she said.

However, the use of PDTs as a monotherapy requires high self-motivation and activation from patients. “Both monotherapy and adjunct therapy applications of prescription digital therapeutics are viable options depending on the severity of the condition, clinical judgment and other contextual factors surrounding the prescription digital therapeutic and the targeted condition,” Salsabili said.

Clinicians must also be trained on the integration of PDTs into existing workflows. They must also be knowledgeable about specific indications and approved treatment areas for PDTs, as well as published clinical evidence and appropriate patients to prescribe PDTs.

When a clinician prescribes a PDT, it’s important to set expectations with the patient, explain the importance of adherence and provide technical training to use the PDT to ensure patients can use the PDT effectively, she said. Once a patient is on a PDT, the clinician should leverage the data and reporting from PDTs to direct follow-up discussions and therapeutic adjustments.

“[PDTs] represent a shift in how therapy is delivered,” Salsabili said. “So appropriate clinical integration by clinicians is critical for optimizing the impact of [PDTs] alongside traditional treatment modalities.”

Access to care

More than specific disease support, PDTs provide continuous remote therapeutic support between clinic visits, allow for personalized and adaptive treatment and monitoring, and improve patient engagement in disease management, according to Salsabili. The interactive nature of PDTs can increase patient motivation, which is crucial for successful lifestyle and behavioral changes required to effectively manage diseases that are targets for PDTs.

Traditionally, the lifestyle and behavioral changes required for effective disease management are difficult to sustain over the long term. The interactivity of PDTs can increase patient motivation and accountability. Currently, disease management is reactive and disjointed, Salsabili said. On the other hand, PDTs have the potential to allow for proactive and coordinated care teams through the use of data sharing among healthcare professionals. A data-driven approach can provide better care coordination and improve overall patient outcomes.

“In the future, [PDTs] have significant potential to drive transformation in medicine by increasing access to evidence-based therapies for underserved populations,” she said. “PDTs can also mitigate financial and income constraints faced by underserved populations as they may potentially offer a cost-effective alternative to traditional therapies, making quality care more accessible and affordable.”

Because PDTs can be accessed remotely, patients and providers can overcome geographic barriers that limit access to care and workforce shortages that limit clinical capacity. PDTs can provide a solution to both the shortage of mental health professionals in certain locations and the strain on the healthcare system due to the rising prevalence of chronic diseases without sacrificing care quality, Salsabili said. “By improving access, adherence, remote monitoring, personalization and coordinated care, PDTs can help compensate for shortcomings in chronic disease care capabilities,” she said.

Payer decisions

There are few payers that have publicly announced coverage of PDTs, although some launched digital health formularies in late 2019. The cost of the product and the cost avoidance through use of the product are both factors that payers consider for PDT coverage. They also consider the clinical evidence available, patient engagement rate and whether the data from the software can be integrated in electronic medical records. “Overall, insurance seeks solid evidence … confirming the therapeutic value and potential cost benefits of reimbursing [PDT]s within existing medical billing codes and policies,” Salsabili said.

Payers that want to support clinicians who are implementing PDTs can publish guidance on covered indications, patient eligibility and any prior authorization criteria, along with approved codes and required documentation. “Payers can develop evidence-based guidelines and clinical protocols, delineating appropriate clinical scenarios and use cases for [PDTs], while aligning with professional society guidance and standards,” she said.

Any coverage updates should be made clear with explanations around the rationale and evidence of a policy change. In addition, payers should highlight any PDTs under consideration or that have been newly approved. Clear communication between payers and providers is critical to optimize successful implementation of PDTs, Salsabili said.

She suggested that payers conduct a two-step preliminary assessment of whether a PDT is promising. First, disease prevalence, effectiveness, safety and cost should be considered, with supplemental criteria considered to determine whether the PDT provides value to other stakeholders. This supplemental assessment should involve the relevant stakeholders, such as patients and providers, to provide input into the PDT and management of patients with the relevant conditions. The payer should then conduct a full product review, similar to a new drug review.

She added that payers should conduct economic evaluations that include cost-effectiveness, budget impact, return on investment and impact on nonclinical and societal outcomes. Currently, there are a limited number of PDTs that have looked at the cost-effectiveness of their products. “[Although] there is a growing number of economic analyses that point to the potential cost-effectiveness of digital therapeutics worldwide, the overall evidence is still emerging across clinical areas,” Salsabili said.

Role of manufacturers

Manufacturers must build the evidence-based rationale and gather stakeholder support to support the rationale of PDT use by payers, providers and patients. They should have comprehensive data from well-
designed randomized control trials that also validate clinical and patient-reported outcomes and include subgroup analyses to identify high-value populations for the PDT, Salsabili noted.

To highlight the overall economic value and return on investment for utilization, manufacturers should conduct cost-effectiveness modeling, such as budget impact analyses and projections of long- and short-term cost offsets.

“Manufacturers should also offer novel value-based contracts, including innovative risk-sharing pricing models, performance guarantees and outcome-based rebate structures aligned to demonstrate value while providing technology-enabled monitoring for value-based agreements,” Salsabili said.

Manufacturers also play a role in patient education and adoption through marketing and promotion of specific therapeutic benefits, user-friendly websites and media explaining how PDTs work. Patient adherence can be encouraged through the use of intuitive app experiences, gamification, social support communities, personalized coaching and transparent data sharing. Plus, ongoing support for technical issues and connectivity, as well as mechanisms to provide user experience feedback to the manufacturer, are all important. “All key stakeholders [and] manufacturers can demonstrate the unique value proposition of [PDTs] and facilitate their practical adoption into routine clinical use,” Salsabili said.

Value-based contracts

Value-based contracts can help manage the risk and uncertainty around real-world adherence and the durability of effects of PDTs, Salsabili explained, and they are becoming more prominent. Some of the models include the following:

• Pay-for-performance models link reimbursement levels to achieved outcomes Shared-risk models are based on real-world performance metrics with patient outcome guarantees
• Outcomes-based models include rebates if the clinical goals are not met
• Risk- and value-based contracts should align stakeholder incentives by connecting the motivations of manufacturers, providers and payers so all are potentially rewarded for patient outcomes and value.

The models not only quantify clinical improvements and economic return on investment, but they also ensure appropriate use by incentivizing providers to prescribe PDTs for the best-suited populations and restrict off-label use, she said.

“[PDT] manufacturers have incentives to ensure appropriate utilization and outcomes under these arrangements as more longitudinal efficacy and economic data become available,” Salsabili said. “Value-based arrangements are expected to grow, facilitating coverage in return for proven real-world cost offsets and clinical benefits.”