FDA regulations and prescription digital therapeutics: Evolving with the technologies they regulate.

Technological progress in digital therapeutics-and, in particular prescription digital therapeutics (PDTs)-has outpaced the processes that the Food and Drug Administration (FDA) uses to regulate such products. Digital therapeutics have entered the health care ecosystem so rapidly that substantial misunderstandings exist about how they are evaluated and regulated by the FDA. This review briefly explains the relevant regulatory history of software as medical devices (SaMDs) and reviews the current regulatory landscape in which prescription and non-prescription digital therapeutics are developed and approved for use. These are important issues because PDTs, and digital therapeutics in general, are an explosively growing field in medicine and offer many advantages over conventional face-to-face treatments for the behavioral dimensions of a wide range of conditions and disease states. By allowing access to evidence-based therapies remotely and privately, digital therapeutics can reduce existing disparities in care and improve health equity. But clinicians, payers, and other healthcare stakeholders must appreciate the rigor of the regulatory frameworks within which PDTs are approved for use.

Prescription digital therapeutics: A new frontier for pharmacists and the future of treatment.

Within digital health, digital therapeutics (DTx) are increasingly used to provide clinical treatment. DTx are evidence-based, U.S. Food and Drug Administration-authorized software to treat or manage medical conditions and are available either via prescription or as nonprescription products. DTx that require clinician initiation and oversight are called prescription DTx (PDTs). DTx and PDTs have unique mechanisms of action and are expanding treatment options beyond traditional pharmacotherapy. They may be implemented on their own or used in combination with a drug and in some cases may be the only treatment option for a particular disease state. This article explains how DTx and PDTs function and how these technologies can be incorporated by pharmacists as they attend to their patients' care.

Evaluation of real-world outcomes associated with use of a prescription digital therapeutic to treat substance use disorders.

BACKGROUND AND OBJECTIVES: Digital therapeutics can expand the reach and fidelity of behavioral treatment for substance use disorders (SUDs). This analysis evaluated real-world engagement and clinical outcomes in patients diagnosed with SUD who were prescribed reSET®, an FDA-authorized prescription digital therapeutic (PDT). METHODS: Patients were prescribed a 12-week PDT comprising 61 therapy lessons (31 "core" and 30 "keep learning" lessons) and contingency management rewards (positive reinforcement message or monetary gift cards) based on lesson completion and negative urine drug screens. Engagement (defined as any activity in the PDT), retention (any activity in Weeks 9-12), and substance use data were collected automatically by the PDT and analyzed descriptively. Associations between early lesson completion and end-of-treatment outcomes were assessed. RESULTS: Six hundred and fifty-eight patients filled their prescription. Evaluated were 602 patients who were exposed to therapeutic content by completing at least one lesson (median age 37 years, 33% female, 41% male, 26% unreported sex). Median lessons completed was 33 (out of 61 possible), and 52% of patients completed all core modules. Retention in treatment during the last 4 weeks of treatment was 74%, and 62% were abstinent (missing data considered positive). [Correction added on 13 December 2022, after first online publication: In the preceding sentence, the treatment percentage values were revised from 74.6% to 74%.] DISCUSSION AND CONCLUSIONS: Patients with SUD exhibited robust engagement with a PDT, high rates of retention through 12 weeks, and substantial rates of abstinence at end of treatment when the therapeutic was used in a real-world setting. PDT's hold promise as a new way to access effective SUD treatment. SCIENTIFIC SIGNIFICANCE: This study is the first to report real-world PDT engagement and clinical outcomes data from a large, geographically diverse population of patients with SUDs.

Assessing the ability of boys with Duchenne muscular dystrophy age 4-7 years to swallow softgel capsules: Clinical trial experience with edasalonexent.

WHAT IS KNOWN AND OBJECTIVE: There is limited information on acceptability of solid dosage forms by young patients with neuromuscular disorders such as Duchenne muscular dystrophy (DMD). Capsule size selection and ability to swallow the NF-κB inhibitor edasalonexent were assessed in males 4-7 years of age with DMD enrolled in clinical trials for a new therapeutic. METHODS: The Phase 3 PolarisDMD randomized, double-blind, placebo-controlled trial enrolled 131 patients from 8 countries. The Phase 2 MoveDMD trial enrolled 31 patients in the United States. As part of enrolment criteria, these trials assessed the ability to swallow softgel 100 mg (~10 mm) or 250 mg (~15 mm) capsules formulated with a phosphatidylcholine-containing coating. Supportive strategies included pill-swallowing techniques and aids. RESULTS: Most (97%; 175/181) patients screened were able to swallow capsules. In Phase 2 and 3, respectively, 77% (24/31) and 61% (80/131) of enrolled patients selected the larger capsule and among those selecting the smaller capsule, most transitioned to the larger capsule. There were no obvious geographical differences in ability to swallow capsules and size selection was not correlated with age. Compliance was high (92%-98%) through 52 weeks of dosing with no discontinuations due to capsule burden. WHAT IS NEW AND CONCLUSION: Swallowing of capsules was not a barrier for drug administration in young patients with DMD. Capsule formulations may be an acceptable alternative to liquid formulations for children as young as 4 years of age.

Economic Burden and Health-Related Quality of Life Associated with Current Treatments for Anaemia in Patients with CKD not on Dialysis: A Systematic Review.

BACKGROUND: The cost and health-related quality of life (HRQoL) burden associated with treatments for anaemia of chronic kidney disease (CKD) is not well characterized among non-dialysis-dependent (NDD) patients. OBJECTIVE: Our objective was to review the literature on costs and HRQoL associated with current treatments for anaemia of CKD among NDD patients. METHODS: The Cochrane Library, MEDLINE, Embase, NHS EED, and NHS HTA databases were searched for original studies published in English between 1 January 2000 and 17 March 2017. The following inclusion criteria were applied: adult population; primary focus was anaemia of CKD; patients received iron supplementation, red blood cell transfusion, or erythropoiesis-stimulating agents (ESAs); and reported results on HRQoL and/or costs. Studies that included NDD patients, did not compare different treatments, and had relevant designs were retained. HRQoL and cost outcomes were summarized in a narrative synthesis. RESULTS: In total, 16 studies met the inclusion criteria: six randomized controlled trials, four prospective single-arm trials, three retrospective studies, one prospective observational study, one simulation study, and one cross-sectional survey. All included ESAs. Treatment of anaemia (compared with no treatment) was associated with HRQoL improvements in five of six studies and lower costs in four of four studies. Treatment aiming for higher haemoglobin targets (compared with lower targets) resulted in modest HRQoL improvements, higher healthcare resource utilization (HRU), and higher costs. CONCLUSIONS: In NDD patients, untreated anaemia of CKD leads to higher costs, higher HRU, and lower HRQoL compared with initiating anaemia treatment. Relative to aiming for lower haemoglobin targets with ESAs, higher targets conferred modest HRQoL improvements and were associated with higher HRU.

Economic and quality of life burden of anemia on patients with CKD on dialysis: a systematic review.

Aims: The overall cost and health-related quality of life (HRQoL) associated with current treatments for chronic kidney disease (CKD)-related anemia are not well characterized. A systematic literature review (SLR) was conducted on the costs and HRQoL associated with current treatments for CKD-related anemia among dialysis-dependent (DD) patients. Materials and methods: The authors searched the Cochrane Library, MEDLINE, EMBASE, NHS EED, and NHS HTA for English-language publications. Original studies published between January 1, 2000 and March 17, 2017 meeting the following criteria were included: adult population; study focus was CKD-related anemia; included results on patients receiving iron supplementation, red blood cell transfusion, or erythropoiesis stimulating agents (ESAs); reported results on HRQoL and/or costs. Studies which included patients with DD-CKD, did not directly compare different treatments, and had designs relevant to the objective were retained. HRQoL and cost outcomes, including healthcare resource utilization (HRU), were extracted and summarized in a narrative synthesis. Results: A total of 1,625 publications were retrieved, 15 of which met all inclusion criteria. All identified studies included ESAs as a treatment of interest. Two randomized controlled trials reported that ESA treatment improves HRQoL relative to placebo. Across eight studies comparing HRQoL of patients achieving high vs low hemoglobin (Hb) targets, aiming for higher Hb targets with ESAs generally led to modest HRQoL improvements. Two studies reported that ESA-treated patients had lower costs and HRU compared to untreated patients. One study found that aiming for higher vs lower Hb targets led to reduced HRU, while two other reported that this led to a reduction in cost-effectiveness. Limitations: Heterogeneity of study designs and outcomes; a meta-analysis could not be performed. Conclusions: ESA-treated patients undergoing dialysis incurred lower costs, lower HRU, and had better HRQoL relative to ESA-untreated patients. However, treatment to higher Hb targets led to modest HRQoL improvements compared to lower Hb targets.