Evidence requirements of permanently listed digital health applications (DiGA) and their implementation in the German DiGA directory: an analysis.

BACKGROUND: With its digital health application (DiGA)-system, Germany is considered one of Europe's pioneers in the field of evidence-based digital health. Incorporating DiGA into standard medical care must be based on evidence-based success factors; however, a comprehensive overview of the evidence required of scientific studies for their approval is lacking. OBJECTIVE: The study aims to, (1) identify specific requirements defined by the Federal Institute for Drugs and Medical Devices (German: Bundesinstitut für Arzneimittel- und Medizinprodukte; BfArM) to design adequate studies, proving a positive healthcare effect, and (2) to assess the evidence given for applications permanently listed in the DiGA directory. METHODS: A multi-step approach was used: (1) identification of the evidence requirements for applications permanently listed in the DiGA directory, (2) identification of the evidence available supporting them. RESULTS: All DiGA permanently listed in the DiGA directory (13 applications) are included in the formal analysis. Most DiGA addressed mental health (n = 7), and can be prescribed for one or two indications (n = 10). All permanently listed DiGA have demonstrated their positive healthcare effect through a medical benefit, and most of them provide evidence for one defined primary endpoint. All DiGA manufacturers conducted a randomized controlled trial. DISCUSSION: It is striking that- although patient-relevant structural and procedural improvements show high potential for improving care, especially in terms of processes - all DiGA have provided a positive care effect via a medical benefit. Although BfArM accepts study designs with a lower level of evidence for the proof of a positive healthcare effect, all manufacturers conducted a study with a high level of evidence. CONCLUSION: The results of this analysis indicate that permanently listed DiGA meet higher standards than required by the guideline.

Oxaliplatin hypersensitivity: evaluation, implications of skin testing, and desensitization.

BACKGROUND: Oxaliplatin hypersensitivity (OXS) presents a challenge in the treatment of oxaliplatin-sensitive malignancies. OBJECTIVE: To analyze patient characteristics of patients with OXS, skin test results, and desensitization outcomes to optimize management. METHODS: Over 5 years, 48 patients with OXS were referred to the allergy/immunology unit at Massachusetts General Hospital. Their clinical reaction patterns were analyzed. Immediate hypersensitivity skin testing was used for risk stratification, and drug desensitizations were performed by using 3 related continuous intravenous protocols that were chosen based on clinical history, skin test reactivity, and the patients' previous desensitization outcomes. RESULTS: OXS occurred in both sexes, with mostly gastrointestinal-related tumors. Hypersensitivity reaction (HSR) onset had occurred during any course of therapy (course nos. 1-28), with a median onset at course no. 8. HSR to oxaliplatin was similar to those observed with cisplatin and carboplatin, including cutaneous, cardiovascular, pulmonary, and gastrointestinal symptoms. However, neurologic symptoms, including tingling, and systemic symptoms, including fever and chills, occurred more often in patients with OXS. Unique to OXS, 2 patients developed drug-induced thrombocytopenia; 1 patients also developed drug-induced hemolytic anemia. Skin testing was positive for the majority of patients with OXS (27/46 [59%]) and correlated with a greater likelihood of developing an HSR during subsequent desensitizations. We safely performed 200 desensitizations in 48 patients with OXS. CONCLUSION: OXS is common with much similarity to other platin agents but also have distinct differences in the onset of hypersensitivity, sex, tumor type, drug-induced hemolytic anemia, and drug-induced thrombocytopenia. Skin testing was helpful for risk stratification. All of the desensitizations were completed successfully.