Development and Application of the Korean version of Medication Regimen Complexity Index (MRCI-K)

Abstract

Background: Polypharmacy may increase medication regimen complexity. The regimens with increased complexity could lead to undesirable health outcomes, such as adverse reactions, hospitalization, and decreased medication adherence. However, verified assessment tools for medication regimen complexity have not been introduced in Korea. The objectives of this research were to develop the Korean version of the Medication Regimen Complexity Index (MRCI-K) and to identify its feasibility as an evaluation tool in a hospital pharmacy practice. Methods: Part 1. Development of the MRCI-K: The development process encompasses cross-cultural adaptation, a reliability analysis and a validity analysis. The cross-cultural adaptation includes translation, back-translation, consolidation by the committee, and pilot testing, which were performed using virtual prescriptions. First, we evaluated the inter-rater and test–retest analysis to confirm the reliability of MRCI-K. In addition, three phases for validation evaluation were performed including convergent validity, discriminant validity, and criterion validity. In the evaluation of validity, the study population consisted of all patients discharged (100 outpatients) from the respiratory medicine ward from January 2016 to March 2016 . Modification of the instructions was introduced in order to evaluate the score in multi-dose dispensing. The convergent and discriminant correlation analyses were conducted to evaluate the validity of the modified MRCI-K as well. To estimate inter-rater reliability, the modified MRCI-K reliability was evaluated with 25 individuals randomly selected from the total sample population. Part 2. Application of MRCI-K: The medication reconciliation study was designed as a prospective, open, randomized controlled study with patients aged 65 or older admitted to the ward of hospital medicine from July 2020 to December 2020. A comprehensive medication reconciliation encompassed medication review based on BEER 2019, a screening tool of older persons' prescriptions (STOPP) and a screening tool to alert to right treatment (START) 2015, recommendations for drug selection, monitoring requirements, renal dose adjustment according to renal function (CrCl) and drug-drug interaction based on Lexicomp®. In addition, the simplification of the instructions of the discharge medication such as food and administration time matching was conducted to reduce the regimen complexity prior to discharge. Adverse drug events (ADEs) were monitored throughout the hospitalization process and follow-up telephone calls to were made to patients 30 days after discharge. The changes of MRCI-K and the modified MRCI-K were compared with the difference in scores between intervention and control groups in order to confirm the pharmacist intervention effect. Results: Part 1. Development of the MRCI-K: The reliability analysis demonstrated excellent internal consistency showing the intra-class correlation coefficient exceeded 0.90 for all cases in the MRCI-K and the modified MRCI-K. Validity was confirmed as a result of a strong correlation between the MRCI-K score and drug number with a Pearson's correlation coefficient of 0.955 and a weak correlation with length of stay (0.242, p < 0.001) and age (0.155, p = 0.005). Criterion validity was confirmed as a result of the good concordance between nine experts’ panel rankings of patient-level medication regimen complexity with the MRCI-K. The validity of the modified MRCI-K was identified as a result of a positive correlation between the modified MRCI score and drug number with a Pearson's correlation coefficient of 0.444 and a weak correlation with diagnosis number (0.134, p = 0.185) and age (-0.262, p = 0.003). Part 2. Application of the MRCI-K: A total of 32 patients were included and 26 patient finished the follow-up 30 days after discharge. Eleven events (34.4%) were reported as drug-related adverse events before the end of the discharge period. Five patients (19.2%) reported drug-related adverse events at the 30-day phone call. Three cases of severe adverse events (SAE) were detected such as hypoglycemia and drug-induced hepatitis. The number of adverse events that were reported on the 30-day phone call was less in the non-intervention group. There were higher scores reduction in the intervention group as compared to the control group in the MRCI-K (-6.2 vs -2.4, p=0.159) and the modified MRCI-K (-2.5 vs 0, p=0.067). We confirmed that the score reduction in the intervention group was greater than that of the control group as a result of the simplification intervention by the pharmacist. Conclusions: Compared with previous studies, this study showed satisfactory validity and reliability of the MRCI-K for the measurement of regimen complexity in Korea. Increased regimen complexity was observed compared to previous studies with polypharmacy, and dosage modification can be a major means of reducing administration time for regimen simplification in hospital pharmacy practice. In the comprehensive medication reconciliation process, we found that regimen complexity was reduced by the simplification intervention, and it could be evaluated as the MRCI-K and the modified MRCI-K. Further studies are needed to use the modified MRCI-K for all patients as an evaluation tool of pharmacist`s intervention.

I. 연구 배경 및 목표 최근 노인 인구와 병존 질환의 증가로 다약제 사용이 증가하고 있다. 사용 약물 개수의 증가는 처방이 복잡해지는 결과를 가져올 수 있다. 처방이 복잡해질수록 약물 부작용이 증가하고, 복약순응도는 저하되며, 재입원률이 높아지는 등 처방의 복잡도는 부정적인 임상 결과와 관련이 있다고 알려져 있다. 해외에서는 임상 약료 서비스의 하나로 복잡한 처방을 간소화하는 중재 연구가 진행되어 왔으나 한국에서는 다약제 사용이 증가함에도 불구하고 그에 따른 처방의 복잡도에 대한 평가와 중재 활동이 이루어지지 않는다. 본 연구에서는 한국형 처방 복잡도 지수(Korean version of Medication regimen complexity index, MRCI-K)를 개발하여 한국의 처방 복잡도 상황을 정량적으로 평가하고자 하였다. 또한 약사의 처방 간소화 중재 결과를 한국형 처방 복잡도 지수로 확인하여 추후 다약제 약물 중재 연구를 위한 기초 자료로 제공하고자 하였다. II. 연구 내용 및 방법 본 연구는 한국 처방 복잡도 지수의 ‘개발’과 ‘적용’, 두 단계로 진행되었다. 한국 처방 복잡도 지수의 개발은 후향적 관찰연구로 디자인되었다. 먼저 처방 복잡도 지수(Mediation regimen complexity index, MRCI)를 근거로 하여 번역과 문화적 적용(Translation and crosscultural adaptation) 과정을 거쳐 MRCI-K를 준비하였다. 2016년 1월부터 3월까지 인하대병원에서 퇴원한 331명의 입원환자와 100명의 외래환자를 대상으로 신뢰도와 타당도 검증을 시행하였다. 또한 병원에서 멀티도즈 단위 (Multi-dose dispensing)로 투약되는 상황을 고려하여 MRCI-K에 지시사항을 추가하여 변형된 한국형 처방 복잡도 지수(Modified MRCI-K)를 준비하였다. 100명의 외래환자를 대상으로 신뢰도와 타당도 검증을 시행하였다. MRCI-K의 적용은 전향적 무작위 배정 연구로 디자인되었다. 2020년 7월부터 12월까지 인하대병원 입원의학과에서 5가지 이상 약제를 투약 중인 65세 이상의 입원 환자를 대상으로 중재 연구를 진행하였다. 입원 중의 약물 중재와 퇴원 시 처방 간소화 활동 후 환자군과 대조군 간의 처방 복잡도 지수의 점수 변화와 보고된 약물 부작용 건수의 차이를 확인하였다. III. 연구 결과 MRCI-K는 높은 신뢰도와 타당도를 나타냈다. 한국의 처방 복잡도는 해외보다 높은 수준으로 전체 점수에서 지시사항에 해당하는 점수가 높은 비중을 차지했다. 변형된 처방 복잡도 지수(Modified MRCI-K)는 높은 신뢰도를 나타냈으나 타당도 결과는 MRCI-K의 타당도 검증 결과와 차이가 있었다. 입퇴원 시기 약사의 약물 중재 활동 결과로 중재군은 대조군에 비하여 전체 처방 복잡도 지수의 감소가 더 컸으며 용법의 간소화로 지시사항에 해당하는 부분의 점수 감소가 가장 컸다. 또한 중재군은 입원 중과 퇴원 후 30일에 확인된 약물 부작용 보고 건수가 대조군보다 적었다. IV. 결론 한국형 처방 복잡도 지수(MRCI-K)는 한국의 처방 복잡도 정도를 정량적으로 평가할 수 있는 지표로 높은 신뢰도와 타당도를 나타냈다. 해외 결과와 비교해 한국의 처방에서 높은 처방 복잡성이 관찰되었으며, 많은 지시사항은 처방 복잡성의 주요한 원인이었다. 처방 간소화 중재 활동의 결과로 처방 복잡도의 감소를 확인하였으며, 이는 MRCI-K와 변형된 MRCI-K점수 감소로 평가할 수 있었다.