Progressing Prescription Software: Finding the Best Path Forward for Adoption of Prescription Digital Therapeutics

Prescription digital therapeutics (PDTs) are software-based treatments that are delivered on a mobile device and have undergone clinical evaluation for FDA authorization.^1,2 PDTs have shown early promise in treating substance abuse disorders, psychiatric disorders, diabetes, and vision impairment in children, along with many other conditions.³ In a recent AJMC Peer Exchange, a panel of experts delved into PDTs, discussing their real-world implementation and coverage, cost savings, and implications for equity and access. The discussion focused on the use of PDTs in mental health. The session was moderated by Robert O’Brien, RPh, senior vice president of specialty pharmacy at Real Endpoints in Canton, Ohio.

Evidence Standards and Policy Considerations for PDTs to Unlock Adoption and Patient Access

PDTs are software-based products used to treat, manage, and prevent diseases; these products comply with standards of Good Manufacturing Practices and have undergone clinical evaluation for FDA authorization.^1,2 PDTs have shown early promise in treating many conditions, including mental and behavioral health disorders, substance abuse disorders (SUDs), diabetes, urinary incontinence, and ophthalmology disorders.³

PDTs can be particularly useful in conditions for which no FDA-approved pharmacotherapies exist (eg, SUDs involving cocaine, cannabis, and methamphetamines) and may also be used to improve adherence to approved pharmacotherapies.¹ Examples of PDTs for SUDs are reSET and reSET-O.⁴ These PDTs deliver an evidence-based therapeutic program combining cognitive behavioral therapy based on the Community Reinforcement Approach,⁵ providing motivational incentives for treatment retention and drug abstinence.1 The efficacy of reSET/reSET-O was evaluated in several clinical trials and real-world studies, demonstrating high rates of retention and abstinence and reduced health care resource utilization.^1,4

Digital health tools represent a growing field.^2,6 As of 2021, there were more than 350,000 digital health-related mobile applications with more than 90,000 new applications added.^2,6 The majority of these can be classed as wellness apps that are publicly available but lack sufficient evidence regarding their design, development, and evaluation.⁷ Fewer than 50 were classified as PDTs that were either available or FDA approved in 2021, with clinical trial results expected for another 150 by 2022.²

Despite FDA clearance, many questions remain about PDTs, including coverage policies, utilization management, contracting strategies, prescriber demand, and optimal coordination of all these aspects for successful adoption.^3,6 There are also delays around key legislation to mandate coverage in Medicare, as the Access to Prescription Digital Therapeutics Act of 2022 has yet to pass the US Congress.^2,8 This bipartisan bill—introduced in the US Senate in 2022—proposes to add PDTs to the list of services and products eligible for coverage under Medicare and Medicaid and would direct the CMS to establish payment methodologies and product-specific Healthcare Common Procedure Coding System (HCPCS) codes for PDTs.^2,8

PDTs are prescribed by treating clinicians and typically delivered on a mobile or wearable device.¹ Although there are many PDTs now on the market, reimbursement is complex.⁹ PDTs are usually covered by health insurance but sometimes by employers, health care providers, and patients themselves.^1,9 PDTs may be covered by insurers under either the pharmacy or medical benefit, but there is uncertainty because of the unique nature of PDTs as intangible products.^3,6 Payment is made using Current Procedural Terminology (CPT)/HCPCS codes.⁹ Value-based payment can enable health care providers to purchase PDTs if they believe they will decrease costs or enhance the value of care that they deliver.⁹

Although there are no current best practices for payers in determining coverage of PDTs, the Medicaid program in Massachusetts has implemented a multistep approach to reviewing PDTs for potential coverage, composed of core and supplemental criteria including disease prevalence, efficacy and safety data, and costs.² These criteria can be a starting point, but standardized frameworks need to be created by payers and benefit managers to prioritize prescription of PDTs.²

Stakeholder Insights

“Similar to other prescription products, digital therapeutics are reviewed and approved by the FDA,” Diana Brixner, PhD, professor at the College of Pharmacy at The University of Utah, said. “Evidence is considered, clinical efficacy and safety [are] evaluated, and these decisions are very much evidence based for approval.… On the other hand, the non-[PDT], like a mobile app, is not reviewed by the FDA, and there is no clinical evaluation of evidence.”

“We would want to define some aspect of efficacy, safety, persistence, [and] adherence to the digital therapeutics that we could then monitor in a way that would let us know whether or not we’re spending the health plans dollars wisely,” added Paul Jeffrey, PharmD, of Jeff℞ey Consulting. “This information could largely be available through claims data.… So we have to see that we’ve paid a claim for a prescription, we’ve paid a claim for a hospitalization, we’ve paid a claim for an emergency department visit.… In case of schizophrenia or another psychiatric illness we can look at recidivism, persistence with treatment on an antipsychotic, [and] doctor and clinic visits.”

“With Medicaid, there is a need for peer-reviewed studies showing the outcomes and the cost savings,” agreed Ashley Peterson, MHA, director for contracting and analytics at Artia Solutions and the former pharmacy director at Florida Medicaid. “For any added service, it needs to be budget neutral or show cost savings. These studies take time but are needed to be able to use PDTs in these populations.”

Real-world analysis of the health plan at The University of Utah Health revealed great potential for savings and better outcomes with PDTs, particularly for patients in more rural environments, who can struggle because of the distance from treatment. “The data [were] really eye-opening and very informative to the health plan to realize the significance of the problem of opioid use disorder, some of the characteristics that drove lack of treatment, and what the benefit of treatment could be to the patient and to overall cost,” explained Brixner.

PDTs could have the greatest impact on or address the most significant unmet needs in disease states where behavioral change is key, for instance in mental health, said Brixner.

Another area she mentioned is complex disease states with complex drug regimens. “Management of drug therapy, improving adherence, giving patients reminders through a [PDT] that help them stay on track with their treatment plan.… Also, diabetes, hypertension, where one of the biggest challenges in treatment [is] that the patient doesn’t always experience daily consequences [and] only sees the consequences years later. There is a huge opportunity for PDTs to raise awareness, on a daily basis, of the importance of taking your medicine, monitoring, and being aware of hidden symptoms,” she said.

There are strategies that payers can use to provide coverage for PDTs and ensure successful implementation, advised Jeffrey. “As a former pharmacy director for the Massachusetts Medicaid program known as MassHealth, we were the first Medicaid program in the country to establish a payment methodology for a [PDT]…. The first products that we adopted were the Pear Therapeutics products reSET and reSET-O.… We entered a risk-based, volume-based contract that would allow us to put a fair amount of risk on the developer.… Because PDTs at the time did not have a national drug code [NDC] for payment, we had to [persuade] the developer to get that information together, create an NDC, and put it in the file that we were subscribing to so that we could then process the claim. We also had to make sure that the prescribers were Medicaid- or MassHealth-eligible prescribers, and then we had to communicate with our prescriber community.

“We required to engage with a certain number of patients for reimbursement,” Jeffrey added. Health care resource consumption was evaluated both 6 months forward and 6 months back for a patient, and that particular patient would be evaluated after a prescription for the reSET or reSET-O. The primary data included emergency department visits, hospitalizations, and detoxification visits, with the individual serving as their own control.

“…We treated about 650 patients, and the health care consumption dropped by 50% post use of the [PDT].” He said real-world analysis showed that “the total apparent cost avoidance for those 650 patients over that period was $722,000 of what we anticipated would’ve been paid.”

Peterson said that even without a waiver for value-based contractors, they were able to have a risk-based agreement, based on engagement. “At Florida Medicaid, I was not able to engage in value-based contracts, we didn’t have a CMS template approved at that time, but…the company provided a pharmacy in the pull-through and the clinical support for the patients,” she said. They were also able to negotiate that they would be charged for only the days that the patient showed engagement and noted the willingness to be flexible. “Manufacturers need to work with the payers to find something that works for each individual,” she noted.

“The same stakeholders as for drugs are involved in reviewing evidence in a health plan and making final decisions on coverage, access, and benefit design, including a provider advocate and a drug information group of PharmDs [who] are evaluating drug therapy,” explained Brixner. “The Digital Center of Excellence [DCOE] is an organization that’s trying to…work with industry and create standards when evaluating these therapies. Certainly, information produced by the DCOE could be reviewed by health plans and their information pharmacists as well. The Peterson Health Technology Institute has partnered with ICER [Institute for Clinical and Economic Review] to do evaluation specifically of digital therapeutics. So there is a framework, and certainly that framework is going to be very useful for those evaluating PDTs in a health plan.”

When reviewing a product for coverage, Artia Solutions evaluates the burden on the provider, added Peterson. “Will there be increased billing and monitoring? Is this something that can be completed successfully without the monitoring of a physician, and what would the outcomes be? Do we have case managers that are trained in this? Are they prepared to accept this and review this information?”

Jeffrey said there was no best practice yet for contracting strategies between payers and PDT developers, “The idea of pulling all the stakeholders together in a process that would result in a document like a contract that you could evaluate the performance of the players—and then who has a stake and a risk in those different parts of the contract—would allow us to demonstrate some success in utilizing that.”

Most insurance companies offer a health plan that has a behavioral health benefit, a pharmacy benefit, a medical benefit, or a durable medical equipment benefit. The PDT must fit these categories to be adopted. “Pharmacy is the only place in the health care system where the pharmacy engagement is adjudicated to a payment status at the point of sale,” he explained. “To get the reSET and reSET-O approved, we had to consider it a durable medical equipment.”

They did not need additional authorization from CMS to adopt this product because the state plan in Massachusetts already considered the pharmacy program purveying durable medical equipment. “We had to overcome some of the obstacles, including an NDC, enrolling prescriber, and enrolling the pharmacy. And we then we had to make sure that our system was configured to recognize the PDT,” Jeffrey added.

Another option would be through the medical benefit, explained Jeffrey. However, “under the medical benefit, the claim isn’t paid until sometime long after the service is delivered,” and the claim risks not being reimbursed. “[PDTs] could be delivered under the medical benefit process, but the adoption there would be an entirely different schema from what I described.… We would literally have no control of it until we saw the claim for it, and then we could deny it. And then we’re not paying the provider for it because they’d have to bundle the service within the encounter they have with the patient,” Jeffrey added.

According to Jeffrey, the fastest path is through the pharmacy benefit, putting it in as an available benefit for all the people in the health plan so there is no added cost. “It is important to have buy-in from a leadership level, from people who are over these silos who can see the big picture with the medical and pharmacy benefit—because you hear the word prescription, and for most of these savings, the offset is not going to be seen in the pharmacy benefit. [We have to] make sure there’s accurate reimbursement for these products and what you’re comparing it to in the patient’s treatment landscape,” Jeffrey emphasized.

Brixner highlighted the need for an integrated delivery system that includes clinicians and providers. “An entire EMR [electronic medical record] system that goes through prescribing and then getting adjudicated through insurance is a process that takes time, perhaps 6 to 9 months. Commercialization and distribution strategies and relationships need to be established far ahead of launch. Big Pharma can adopt those processes to a particular product because they know who the thought leaders and the decision makers are.”

Strategies for Appropriate PDT Integration and Utilization

At a recent multistakeholder forum that included representatives from payers, pharmacy benefit managers, integrated delivery systems, patient advocacy, PDT innovator organizations, health economists, and academics, participants were asked to identify areas of opportunity around coverage and use of PDTs and to provide input to assist health care decision makers in making PDT coverage decisions.⁶

Participants identified standardizing product definitions and categorization across the PDT industry; emphasizing the value of regulatory approval in establishing standards of evidence for PDTs; establishing evidence frameworks to guide coverage and reimbursement decisions for PDTs; considering unique PDT product aspects such as data security, privacy, and product updates; advancing awareness and professional expertise in PDTs among all health care stakeholders; and promoting PDT adoption and equitable access as areas of opportunity.⁶ Because the appropriate benefit placement for coverage of PDTs may not fit precisely into the existing benefit category paradigm of medical, pharmacy, or durable medical equipment, a new stand-alone digital benefit category may be needed.⁶

Stakeholder Insights

“What needs to happen on a larger scale is that CMS needs to come out and address and provide support for all payers,” said Peterson. She added that the other commercial payers should look at what Medicare and Medicaid are doing. Providing more guidance and support can allow for improved communication and increased awareness. Another important aspect is standardized coding: Should it be under medical benefit or pharmacy benefit, or is it therapy or durable medical equipment?

“Providers will need to believe that there’s benefit and have the motivation to prescribe,” said Brixner, adding that with a PDT, there are a lot of practical questions. “What is the code that you need to use? Has that been adapted by the EMR system? Is it in the list? Can I choose it and it automatically gets prescribed? And then how does my patient access the PDT? As the provider’s having that dialogue with the patient, the patient has their concerns and doubts as well, and the provider needs to address those and make sure the patient feels comfortable that they will be able to access the product and how to use it,” she said.

The provider should be educated so they can answer questions from the patient about the potential benefits and concerns. Brixner believed a provider advocate could speed up the coverage process by explaining the benefits to the health plan. “Probably 2 years out from an anticipated launch, you need to have a provider advocate that can help you navigate this, the required processes to get a PDT available, [including] the process to have it entered into an EMR to be able to prescribe it. Those things need to be addressed very early on,” she said. Brixner added that providers do not need to know about a product until it is available and covered for patients, but that once it is, education is needed on the benefit, prescribing information, and administration “in a peri-launch type of a time frame. [Education will be] ongoing as real-world evidence becomes available.”

Jeffrey explained that at MassHealth they “have certain processes in place,” when it comes to prescriber education. “We have all our policy decisions published on our website, and that gets updated frequently.” They also used a prescriber letter, which was selectively sent to their prescriber population and that specifically mentioned reSET and reSET-O. This was targeted at addiction treatment and behavioral health. Their partner, Pear Therapeutics, was able to send out press releases and would help distribute the prescriber letter.

When it comes to payers tracking data on the utilization of the PDT and using that to adjust policies or coverage decisions, Peterson thinks this is still relatively unexplored. “So just having somebody to dig into the data and make use of what you’re receiving, there’s no other study that can show outcomes like this. With patient engagement and just making sure that the payer has access to the data and has the abilities through whatever contract mechanism they’ve decided to adjust to get the best use out of the products. I really think that the sky is the limit here with all of these products. And by having a flexible design, a flexible contract, [and a] flexible payment system, I think that that’s the kind of support that the payers need.”

Jeffrey mentioned that JeffRey Consulting recently created a pipeline-monitoring process with a budget impact forecast for prescription drugs, “which is now very robust.” They included PDTs in that process.

“We look at products that are in development or in clinical trials, determining whether we want to evaluate it. We created an algorithm for evaluating PDTs within our team so that we would have all the tools when it came to the contracting piece and the monitoring piece in place,” said Jeffrey.

He added that it was in the interest of the developer to let them know about the product as soon as possible. Then the payer has time to react, provide feedback, and flag what needs to happen before they get to market, for instance the need for an NDC.

Jeffrey added that an example of an outcomes-based agreement is a contract that makes a payment based on evidence generation by the payer, providing benefits to the company. “In our experience, the payer was very excited to have us publish our results. We had agreements like that with certain pharmaceutical companies,” said Jeffrey. He thinks that this may be a new opportunity that benefits different stakeholders. “Also, these digital therapeutics are sometimes used alongside drug therapy. We could think about using the digital therapeutic as support for adherence with the drug therapy, so the contract would include both,” he noted.

Jeffrey added that this would be particularly relevant for psychiatric disorders including major depressive disorder and schizophrenia. “Behavioral health issues are notoriously difficult for adherence and certainly major depressive disorder, but even more so schizophrenia. where recidivism and lack of adherence are major issues.” He thought it was another win-win opportunity: “Good for the patient, good for the company, good for the plan. I’m excited to see this coming and I almost wish I was in the trenches again so I could be thinking about what kind of contracts I could figure out.”

Brixner added that knowledge of the Academy of Managed Care Pharmacy (AMCP) dossier is needed. “Big Pharma has experience with the AMCP dossier. They fill it out for every product to begin to address coverage. [In April], at the AMCP meeting, Format 5.0 [was] announced, which includes a framework for the assessment of digital therapeutics. For the Big Pharma companies, this will be a quick uptake. But smaller companies will need the education on what the format is, why and how they need to do this, and what the resources are to complete it… So I think that’s another example of the increased facilitation by Big Pharma partnering with PDTs as far as access and information.”

Optimizing Access and Compatibility for Improved Outcomes

It is recognized that low uptake is a major challenge for manufacturers and payer groups as these products become incorporated into practice.² Working together with health systems and providers by using directed education and workflow support about the product can help increase access to the appropriate population.² Equitable recruitment of study participants most likely to benefit from PDTs is also important.² It is recommended that manufacturers work in collaboration with providers to provide workflows, continuing education, and training programs, and make these accessible to various stakeholders to ensure the appropriate use of their products.²

Coproduction of PDTs with providers and stakeholders can be a solution to increase uptake, engagement, and health care outcomes, with the aim of placing end users at the heart of the process.⁷ Recommendations for coproducing PDTs for mental health include involvement of a diverse stakeholder group, involvement at all stages, inclusivity and consideration of roles, balancing suggestions and fidelity, and the inclusion of collaborative creative and “think aloud” methods to allow for authentic feedback.⁷

Stakeholder Insights

On how payers determine whether they are optimally providing coverage on the pharmacy or the medical benefit when they are considering a PDT, Peterson thought coding is important to enhance patient access and adoption of PDTs for patients. “Previously I was left with only 1 option to cover through the pharmacy point of sale. We had barriers on the medical side, some of the durable medical equipment or therapy, or different benefits that [Jeffrey] described. With more guidance and parameters, we can outline flexibility. We’re still so new in this process that payers that do want to provide coverage are just looking to give the patient access however they can.”

“At MassHealth, when we made the benefit available, it had to be available to everybody. All of our patients, all of our providers had to have the authority to prescribe it unless we decided to restrict it, which we did not,” explained Peterson. “We worked with particular providers to make sure we kept them informed all the way because they had 3 very large clinics across the state. We worked with the Bureau of Substance [Addiction] Services in the Department of Public Health, and they had directed dozens of clinics and had influence over most of the behavioral health clinics that were supported through public funds. So that became our way of getting the word out there, and they became some of our best advisers in terms of how we were going to launch.”

Jeffrey added that stakeholder engagement is important. “If we were to launch the major depressive disorder or schizophrenia product, I would work with our Department of Mental Health because it was a sister agency, and we had a long-standing relationship with how we make products available in the mental health space with them. Having that kind of relationship and bringing people in as early as possible is vital.”

“Teaching PharmD students, and other graduate students about digital therapeutics, is another area of how we bring professionals-in-training up to speed on PDTs,” Brixner explained. “There is so much in the literature, but it almost becomes overwhelming as far as how many different ways you can evaluate evidence and generate evidence for digital therapeutics…. The good news is the information’s going to keep on coming. My advice is to keep an eye on the literature for what’s being published to help us all in understanding how to best evaluate and generate evidence for digital therapeutics.”

All stakeholders agreed that PDTs have a role in mitigating or reducing health care disparities and inequities in access to treatment or health outcomes across different populations. “We can look at examples like telehealth, which since [COVID-19] has taken a huge leap forward,” said Peterson. “I think it’s going to take a major payer or a federal initiative to give some legitimate coverage, guidance, or support to advance this to the level where it needs to be and where it can thrive. In the meantime, we’re all doing all this work behind the scenes. Great studies are being published, but now it needs to be noticed on a larger stage for wide-scale adoption.”

Brixner added that she expects the combination of drug therapy and digital therapeutics to result in “improved outcomes, lower-overall-cost holy grail of treatment and disease management.” Regarding health disparities, she said that “it’s going to provide access to people that typically have had challenges accessing health care. I think having the ability to manage your disease on a phone where you can have access to it immediately is going to be a huge step forward."

“It’s going to provide access to people who typically have had challenges accessing health care. So I think it’s a big win for Medicaid,” added Jeffrey.

“I think that what is missing in our health care system is, as the patient, we’re so disconnected from this product or service that is being given to us, we don’t know how to access it. We don’t know how to utilize it,” Peterson said. “We know how expensive it is when patients access the wrong level of care. Continued engagement really emphasizes patients seeking the appropriate level of care, following up with primary care, and then having a device reminding them of consistent treatment so they don’t end up in an emergency situation where they’re monitoring their mental health, which results in improved physical outcomes. So really looking at the whole person and what these products can provide,” Peterson added.

Raising awareness is the biggest advantage if Congress passes the Access to Prescription Digital Therapeutics Act, said Brixner. “The adoption of this act won’t necessarily mean that all PDTs are covered by CMS organizations, but it is a recognition that there is a potential of benefit,” she said. She said any individual plan covering Medicare and Medicaid patients, or any other patients covered by CMS, should be evaluating this and making a proactive decision on whether this can benefit their members.

“In our health care ecosystem, one of the first questions that gets asked is, is my insurance going to cover this? Right. So, if the answer to that is no, then it’s going to be an impediment to access,” Jeffrey said. The Prescription Digital Therapeutics Access Act provides a framework for solving this and establishes a pathway for insurer coverage, added Jeffrey, which should greatly improve access. “I believe it’s critically important to have PDTs recognized by another branch of the federal government; CMS, for example. The FDA is all on board, and they have a great suite of services around digital therapeutics. Time for the partnership to marry up so that our patients can have access to this promising therapy.”

All agreed on the potential of PDTs. It would be “a win-win situation for developer providers, patients, and insurance companies,” said Brixner.

“I think it’s hard to envision a future where digital health isn’t more a part of our day-to-day life,” added Jeffrey. “It’s inevitable that we will see digital therapeutics become perhaps as commonplace as drug therapy, but we’re stalled at the moment, and I think that we need to break that open. I think that bigger pharma companies getting involved might be that point, but certainly governmental approval…is essential.”

Peterson emphasized the need for a champion within the community for maximizing PDT coverage access, “whether it be mental health or addiction, having that support from the community, [or] bringing in whatever partners you can to support coverage through the payer space.”

References

1. Xiong X, Braun S, Stitzer M, et al. Evaluation of real-world outcomes associated with use of a prescription digital therapeutic to treat substance use disorders. Am J Addict. 2023;32(1):24-31. doi:10.1111/ajad.13346

2. Salsabili M, Tesell M, Alcusky M, et al. Prescription digital therapeutics: applying Medicaid experience to value assessment and formulary management. J Manag Care Spec Pharm. 2023;29(6):685-691. doi:10.18553/jmcp.2023.29.6.685

3. Lumbreras AG, Hurwitz JT, Liang X, et al. Insights into insurance coverage for digital therapeutics: a qualitative study of US payer perspectives. J Manag Care Spec Pharm. 2024;30(4):313-325. doi:10.18553/jmcp.2024.30.4.313

4. Velez FF, Ruetsch C, Maricich Y. Evidence of long-term real-world reduction in healthcare resource utilization following treatment of opioid use disorder with reSET-O, a novel prescription digital therapeutic. Expert Rev Pharmacoecon Outcomes Res. 2021;21(4):519-520. doi:10.1080/14737167.2021.1939687

5. Meyers RJ, Roozen HG, Smith JE. The community reinforcement approach: an update of the evidence. Alcohol Res Health. 2011;33(4):380-388.

6. AMCP partnership forum: the evolving role of digital therapeutics. J Manag Care Spec Pharm. 2022;28(7):804-810. doi:10.18553/jmcp.2022.22093

7. Brotherdale R, Berry K, Branitsky A, Bucci S. Co-producing digital mental health interventions: a systematic review. Digit Health. 2024;10:20552076241239172. doi:10.1177/20552076241239172

8. Access to Prescription Digital Therapeutics Act of 2022, S 3791, 117th Cong (2021-2022). Accessed May 11, 2024. https://www.congress.gov/bill/117th-congress/senate-bill/3791

9. Powell AC, Bowman MB, Harbin HT. Reimbursement of apps for mental health: findings from interviews. JMIR Ment Health. 2019;6(8):e14724. doi:10.2196/14724