A Hybrid Type III Effectiveness-Implementation Trial to Optimize Medication Safety With Oral Antitumor Therapy in Real-World: The AMBORA Competence and Consultation Center.

PURPOSE: Implementation science endeavors to facilitate the translation of evidence-based research into clinical routine. The clinical pharmacological/pharmaceutical care program evaluated in the randomized AMBORA trial on medication safety with oral antitumor therapeutics (OAT) optimizes care delivery and provides significant benefits for patients, treatment teams, and health care systems. Thus, we aimed to investigate the implementation of this care program within the AMBORA Competence and Consultation Center (AMBORA Center). METHODS: The AMBORA Center within a University Comprehensive Cancer Center offered several services (eg, patient consultations) and was evaluated according to the RE-AIM framework. This multicenter hybrid type III trial focused on implementation outcomes (eg, patient recruitment, referring units, evaluation of services) while concurrently investigating effectiveness (eg, side effects, medication errors). Quantitative and qualitative assessments were combined. RESULTS: The AMBORA Center conducted over 800 consultations with 420 patients in seven institutions. The primary end point of counseling 70% of patients treated with OAT was not reached. Patients were referred by 15 treatment units compared with 11 units in the AMBORA trial. On the basis of heterogeneous referral rates and characteristics across the institutions, barriers and facilitators of the implementation process were derived. Several survey results (eg, stakeholder interviews, online/paper-based questionnaires) reflected a high appreciation of services by patients and health care professionals. The severity of 60.1% (178 of 296) of detected side effects improved, and 86.3% (297 of 344) of medication errors were resolved. CONCLUSION: Despite not reaching the primary implementation outcome, the AMBORA Center included more treatment units and demonstrated patient benefit of the AMBORA care program by meeting all effectiveness outcomes. We outlined quantitative and qualitative implementation characteristics to enhance outreach and foster further dissemination of centers to optimize medication safety with OAT.

From the Randomized AMBORA Trial to Clinical Practice: Comparison of Medication Errors in Oral Antitumor Therapy.

The randomized AMBORA trial showed that medication errors are frequent in patients treated with oral antitumor therapeutics and that they can be substantially reduced by an intensified clinical pharmacological/pharmaceutical care program. While randomized controlled trials are essential to generate clinical evidence, their generalizability in real-world is not always given. The AMBORA care program was implemented in clinical routine within the AMBORA Competence and Consultation Center (AMBORA Center) at the Comprehensive Cancer Center Erlangen-EMN, allowing a thorough comparison of medication error frequencies and characteristics. Our primary analysis compared data at therapy initiation of new oral antitumor therapeutics from the AMBORA trial intervention group (n = 98) and the AMBORA Center (n = 142). Medication errors involving the oral antitumor therapeutics were twofold higher in real-world compared to the randomized controlled trial (mean 0.83 ± 0.80 per patient vs. 0.41 ± 0.53, P < 0.001). We observed more complex oral antitumor therapeutic regimens, a higher median number of medications, and a higher ECOG status in clinical routine vs. the randomized trial. A high percentage of medication errors was completely solved in both groups (85.7% vs. 88.3%, ns). Medication error characteristics within the complete medication (oral antitumor therapeutics and concomitant medication) were similar in both groups (e.g., patient-related causes, drug-drug/drug-food interactions). Taken together, medication errors were even more frequent in clinical routine than in the randomized controlled trial and a high rate was solved in clinical routine by a clinical pharmacological/pharmaceutical care program.

Optimizing Medication Safety with Oral Antitumor Therapy: A Methodological Approach for the Real-World Implementation of the AMBORA Competence and Consultation Center.

Generating evidence for the efficacy of an intervention is not sufficient to guarantee its implementation in real-world settings. The randomized AMBORA trial (Medication Safety with Oral Antitumor Therapy) demonstrated that an intensified clinical pharmacological/pharmaceutical care program has substantial benefits for patients, treatment teams, and the healthcare system. Thus, we are now investigating its implementation into routine care within the AMBORA Competence and Consultation Center (AMBORA Center). We perform a multicenter type III hybrid trial following the RE-AIM framework to assess the clinical effectiveness of this care program under real-world conditions, while evaluating the implementation outcomes. Semi-structured stakeholder interviews based on the Consolidated Framework for Implementation Research (CFIR) have been conducted to identify barriers and facilitators. So far, 332 patients treated with oral antitumor drugs have been referred to the AMBORA Center by 66 physicians from 13 independent clinical units. In 20 stakeholder interviews (e.g., with clinic directors), 30% (6/20) of the interviewees anticipated possible barriers which may partly hinder sustainable implementation (e.g., unavailable consultation rooms). Furthermore, important facilitators (e.g., operational processes) were identified. This methodological description adds knowledge on how to structure a hybrid effectiveness-implementation trial and proposes multilevel implementation strategies to improve the medication safety of oral antitumor therapy.

New Oral Antitumor Drugs and Medication Safety in Uro-Oncology: Implications for Clinical Practice Based on a Subgroup Analysis of the AMBORA Trial.

Oral antitumor therapeutics (OAT) bear a high risk for medication errors, e.g., due to drug-drug or drug-food interactions or incorrect drug intake. Advanced age, organ insufficiencies, and polymedication are putting uro-oncological patients at an even larger risk. This analysis sets out to (1) investigate the frequency and relevance of medication errors in patients with prostate cancer or renal cell carcinoma treated with OAT and (2) compile recommendations for clinical practice. This post-hoc subgroup analysis used data collected in the randomized AMBORA trial (2017-2020; DRKS00013271). Clinical pharmacologists/pharmacists conducted advanced medication reviews over 12 weeks after initiation of a new oral regimen and assessed the complete medication process for drug-related problems. Medication errors related to either the OAT, prescribed or prescription-free concomitant medication, or food were classified regarding cause and severity. We identified 67 medication errors in 38 patients within the complete medication within 12 weeks. Thereof, 55% were detected at therapy initiation, 27% were caused by the patients, and 25% were drug-drug or drug-food interactions. Problem-prone issues are summarized in a 'medication safety table' to provide recommendations for clinical practice in uro-oncology. Tailored strategies including intensified care by clinical pharmacologists/pharmacists should be implemented in clinical practice to improve medication safety.