Economic analysis of allogeneic hematopoietic stem cell transplantation in the Bone Marrow Transplant Center of Tunisia.

Introduction: New procedures and diagnostic tests in hematopoietic stem cell transplantation (HSCT) are associated with a significant increase in costs. The last cost estimate of allogeneic HSCT done in Tunisia was in 1996 and concerned only direct medical costs. Therefore, an updated cost analysis is needed. Objective: Analysis of direct costs during the first-year post-allogeneic HSCT in two groups of patients: Bone Marrow Transplant (Allo-BMT) and Peripheral Blood Stem Cell Transplant (Allo-PBSCT) and identification of factors leading to interindividual variations in costs in order to compare these costs with the budget allocated by the payer (CNAM). Methods: Pharmacoeconomic retrospective study, concerning patients who underwent allogeneic HSCT in 2013. Clinical and unit cost data were obtained from medical and administration records. Results:This study showed that the average direct cost of allogeneic HSCT in the population during the first year reached 56 638€. The average cost of Allo-BMT was 63 612€, and Allo-PBSCT was 45 966€ (p > 0.05). The initial hospitalization counted for 88% of total direct cost with an average cost of 41 441€ in Allo-BMT and 24 672€ in Allo-PBSCT (p < 0.05). Direct medical costs represented more than 70% of total direct costs, drugs, and laboratory tests occupied the largest share. Antifungals, antitumors, and antiviral drugs were the most expensive pharmaceutical classes with a mean cost, respectively, of 4 526€; 3 737€ and 3 268€. Some clinical criteria were significantly related to total direct costs like length of aplasia (p < 0.01) and GVHD (p < 0.05). However, the type of blood disease, its risk, length of mucositis, and the treatment protocol have no effect on the costs for all allogeneic patients. Conclusion: Our results showed that the costs of Allo HSCT have exceeded by far the budget allocated by the CNAM to the center, since the 90s to this day. That's why the total reimbursement mechanism should be revised.

Regulatory Challenges in the COVID-19 Era: The Case of Tunisia.

In view of the possible disruptions in the manufacturing and supply of health products following the coronavirus disease 2019 (COVID-19) pandemic, the Tunisian medicines regulatory authority was mobilized to guarantee patient safety. Teleworking has become the ultimate way of service continuity. The planning was revised according to health priorities. Work procedures were set online. A minimum list of medicines known as "medicines of health and strategic interest" was established. The Directorate of Pharmacy and Medicines (DPM) has been working on updating medicines stock data. A provisional suspension of authorizations for medicines export for 1 mo was decided. A fast-track procedure allowing the validation of alternative sources of raw materials has been put in place. An appeal for a fast track manufacture of hydroalcoholic gel/solutions was launched. A Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI) procedure has been adopted in order to dispense off-label prescriptions of hydroxychloroquine and azithromycin combination. Focus groups were organized in order to set up therapeutic trials exploring possible strategies of COVID-19 treatment, such as serotherapy and BCG vaccine. This proactive and anticipatory policy has made it possible to meet the health challenges dictated by this crisis.

Valuing health-related quality of life using a hybrid approach: Tunisian value set for the EQ-5D-3L.

OBJECTIVE: To develop a value set for EQ-5D-3L based on the societal preferences of the Tunisian population. METHODS: A representative sample of the Tunisian general population was obtained through multistage quota sampling involving age, gender and region. Participants (n = 327), aged above 20 years, were interviewed using the EuroQol Portable Valuation Technology in face-to-face computer-assisted interviews. Participants completed 10 composite time trade-off (cTTO) and 10 discrete choice experiments (DCE) tasks. Utility values for the EQ-5D-3L health states were estimated using regression modeling. The cTTO and DCE data were analyzed using linear and conditional logistic regression modeling, respectively. Multiple hybrid models were computed to analyze the combined data and were compared on goodness of fit measured by the Akaike information criterion (AIC). RESULTS: A total of 300 participants with complete data that met quality criteria were included. All regression models showed both logical consistency and significance with respect to the parameter estimates. A hybrid model accounting for heteroscedasticity presented the lowest value for the AIC among the hybrid models. Hence, it was used to construct the Tunisian EQ-5D-3L valuation set with a range of predicted values from - 0.796 to 1.0. CONCLUSION: This study provides utility values for EQ-5D-3L health states for the Tunisian population. This value set will be used in economic evaluations of health technologies and for Tunisian health policy decision-making.

Physical and chemical stability of cytarabine in polypropylene syringes.

BACKGROUND: Cytarabine is widely used to treat leukemia and lymphoma. Currently, Cyrabol®, powder for injection, is one of the specialties marketed in Tunisia. However, no stability data when diluted with 0.9% NaCl are available. The aim of this study is to evaluate the physical and chemical stability of cytarabine (Cyrabol®) solution after dilution in 0.9% NaCl (1 mg/mL, 5 mg/mL and 10 mg/mL) in polypropylene syringes under different storage conditions. METHODS: Cytarabine solutions (1 mg/mL, 5 mg/mL and 10 mg/mL) in 0.9% NaCl were prepared in polypropylene syringes and stored for 28 days under different conditions. Cytarabine preparations in glass containers were prepared as a control to detect any adsorption. Chemical stability was assessed by a stability-indicating high-performance liquid chromatography method. The stability-indicating capacity of the method was proved by forced degradation tests. Linearity, precision and limit of detection and quantification were performed according to the International Conference on Harmonisation recommendations. Physical stability was checked by visual inspection. RESULTS: The method was proven to be a validated stability-indicating assay. At 2-8°C, all tested solutions were chemically stable for 28 days. However, at 25°C, the main degradation product gradually increased during the study and the chemical stability of 1 mg/mL, 5 mg/mL and 10 mg/mL solutions was 14 days, 8 days and 5 days, respectively. Similar results were observed in the glass containers. CONCLUSION: The highest physical and chemical stability of cytarabine diluted in 0.9% NaCl in polypropylene syringes was observed at 2-8°C. At 25°C, better stability was found in the 1 mg/mL solution compared with those at higher concentrations (5 mg/mL and 10 mg/mL).

Perception of hematologists and oncologists about the biosimilars: A prospective Tunisian study based on a survey.

INTRODUCTION: Biosimilar drugs have significantly shaken the global pharmaceutical market through a better access to the health care services. The aim of this study is to establish a state of play in Tunisia based on the knowledge and perceptions of doctors on biosimilars in order to identify the problems related to these drugs and to propose solutions for improvement. MATERIALS AND METHODS: In our study, we conducted a prospective, descriptive survey using a questionnaire, destinated to oncologists and hematologists with different grades, from both public and private sectors and from several regions. The questions focused on physicians' general knowledge of biosimilars and their comparison with reference on safety, quality, efficacy, and indication. Finally, we explored the proportion of physicians who are favorable to the policy encouraging biosimilar use. RESULTS: One hundred and seven doctors among 150 answered the questionnaire; 57% were oncologists and 43% were hematologists. About one over five physicians defines biosimilar as a chemical drug. About 29% do not differentiate between a biosimilar and a generic one. A percentage of 68 believe that a biosimilar can have all the indications of its reference following complementary clinical studies. On the other side, 68.2% support the policy encouraging these drugs. Last, only 3.7% of the practitioners believe that they are well informed about biosimilars. DISCUSSION: Our results are comparable to other surveys described in the literature. However, this is the first study that targets oncologists and hematologists specifically. CONCLUSION: Our study showed a lack of information from oncologists and hematologists about biosimilars in Tunisia. Thus, health authorities should carry out training programs on biosimilars and introduce clear and effective legislation in order to allow better access to health care services.

Parenteral Nutrition Complications in Children Undergoing Bone Marrow Transplantation.

BACKGROUND: Parenteral nutrition (PN) seems to be a practical solution to face the negative nutritional effects of bone marrow transplantation. OBJECTIVE: Report and describe all observed PN-related complications in children undergoing allogenic bone marrow transplantation in a tertiary center and determine the possible risk factors. MATERIALS AND METHODS: This was a retrospective and observational study including 51 allografted children 2 to 17 years of age. We collected from medical patient records any noticed PN-related complications using an assessment causality method. The independent risk factors for complications were investigated by multivariate analysis. RESULTS: A total of 92% of patients (n=47) developed a total of 136 complications attributable to PN. The incidence rate of complications was 5 for 100 patient days of PN. Infectious complications (32.3%) and electrolytic disorders (27.9%) were the most common conditions identified during our study. Multivariate analysis showed that the duration of PN exposure, age, and hyperglycemia were the risk factors for the onset of these complications. CONCLUSIONS: Although we have noticed multiple complications attributable to PN, a certain causal link is difficult to establish in this particular context. Emphasizing enteral nutrition in bone marrow graft protocols would be the best way to avoid these complications.

Direct cost analysis of the second year post-allogeneic hematopoietic stem cell transplantation in the Bone Marrow Transplant Centre of Tunisia.

Background: Hematopoietic stem cell transplantation (HSCT) is a medically complicated therapy with a long recovery time. In Tunisia, the National Health Insurance Fund (CNAM) covers only the first year post-transplantation, after which the costs are borne by the hospital. Objective: Describe complications that can occur during the second year post-allogeneic HSCT and calculate direct costs in different groups of patients. Methods: In this pharmacoeconomic study, medical records of the second year post-allogeneic HSCT were collected. Studied variables included frequent observed complications and medical and non-medical direct costs. Results: The average total direct cost in the population during the second year post-transplantation was $11,571, 97% of which represents direct medical costs Drugs accounted for the largest share (80%) of total direct costs, dominated by the cost of antifungals (52%) and antivirals (26%) drug . Cytomegalovirus status was seen in 9.3% of patients and was associated with a seven-fold increase in direct costs (p < 0.001).​​In patients who developed chronic GVHD, the average direct cost was three times higher than for those who did not (p = 0.032). Conclusion: Given the importance of direct costs in the post-transplantation period a review of the hospital financing mechanism and a new convention with the CNAM is crucial.​​.