Identification and characterisation of drug-related problems and its clinical and cost implications in transfusion dependent thalassaemia patients

Abstract

Thalassaemia is the most common monogenic disease that imposes a significant health burden. Management of these patients has been challenging and complicated by drugrelated problems (DRP). However, there is limited published data on the incidence and implications of DRP in transfusion dependent thalassaemia (TDT) patients. This study aimed to evaluate the burden, associated factors, and impacts of DRP on TDT patients. A systematic review of articles reporting epidemiology, factors, and implications of DRP on haematological patients was conducted as there was limited published DRP data on TDT patients. The search was conducted on Pubmed, Embase and Scopus databases from inception to 01 March 2022. Then, a cross-sectional observational study was conducted in the outpatient department of a tertiary hospital. Descriptive analysis was used for the characterisation of DRP. Logistic regression was used to assess the factors associated with DRP while the Mann-Whitney U test and Chi-square test were used to evaluate the clinical and cost implications. For the systematic review, 1417 articles were screened, and 14 articles on haematological diseases were included. A median DRP incidence of 68.65% (Interquartile Range, IQR 55.58; 86.08) was reported. The most common DRP reported in the review were “treatment effectiveness” (n=2723; 45.8%) and “treatment safety” (n= 2486; 41.8%) with polypharmacy and treatment complexity being positively associated with DRP. In the cross-sectional study among TDT, 150 patients (75%) out of 200 participants were affected by DRP. Treatment effectiveness (n= 172, 55.8%) was the most common DRP, followed by treatment safety (n= 122, 39.6%). Three factors significantly associated with DRP were medication regimen complexity index (MRCI) > 17.5 (Adjusted Odds Ratio, AOR 4.99, 95% CI: 1.934-12.87), blood transfusion of four weekly or less (AOR 3.69, 95% CI: 1.646-8.27), and Malay ethnicity (AOR 3.08, 95% CI: 1.36-6.97). Patients with DRP had significantly higher median serum ferritin levels (3833.02 μg/L) than those without DRP (1104.98 μg/L) (U=6591.50, z= 8.017, p-value<0.001). Interestingly, DRP acted as a full mediator in the association between MRCI and iron overload, with a significant Z mediation score value of 3.19. The annual medication cost in DRP patients was significantly higher than that without DRP (Median= MYR19,366.63, IQR: 7175.64- 26,684.76; Median=RM 3682.32, IQR: 2631.01-24,025.56) (U=4795.5, z= 3.038, p=0.002). Overall, DRP is prevalent in TDT patients, especially those related to treatment effectiveness, and has significant implications for both clinical and cost implications. Notably, our study highlighted the importance of controlling medication complexity to improve treatment outcomes, especially among patients with DRP. Future efforts in managing and preventing DRP in TDT patients are therefore warranted for improved clinical and cost implication.