MULTIPLE FIRST-LINE TREATMENTS (MFT): WHY ARE THEY CRITICAL AND HOW CAN THEY BE IMPLEMENTED? PRASHANT YADAV The William Davidson Institute, University of Michigan,USA
Multiple First-Line Therapies (MFT) for Malaria When more than one drug is employed in a population at any given time, simulation models show that the emergence and spread of resistance is delayed (Laxminarayan et al 2006), Boni et al, 2008 Under MFT several therapies are available and prescribers/caregivers/end-patients determine which therapy to use according to preset guidelines
Multiple First Line Treatments : the tradeoffs Delayed emergence and spread of resistance Increase in overall treatment seeking Multiple First Line Treatment Higher costs of program implementation Higher cost of procurement, inventory holding We need to better understand the costs and benefits of MFT
Fraction of population resistant to drug in use Drug variety and resistance: Preliminary model 100 90 10 years 20 years 80 70 60 50 40 30 20 10 0 0 1 2 3 4 5 6 7 8 9 10 Number of drugs
Choice modeling to understand treatment seeking under drug variety Anti-malarial products are perceived as bundles of characteristics Prescriber/caregiver/patient preferences are defined on these characteristics rather than on the products themselves Preference spectrum : the space of all possible combinations of levels of attributes, where each point corresponds to a potential product location in the category Each prescriber/care-giver/patient is characterized by the specification of its most preferred anti-malarial in the preference spectrum Antimalarial B Ideal point on Attribute1 for a population/patient segment Antimalarial A Attribute 1 e.g. number of doses
Choice model details A patient i with most preferred drug x i associates a utility U ij to a product j in the assortment U ij = Z p g( x i b j ) Z is a positive constant representing the benefit associated with taking an antimalarial with high efficacy. p is the price of product Patients choose the variant with the highest utility among the set {U j : j S {0}} A no-treatment option, denoted by j = 0 occurs if the patient does not derive positive utility from any option i.e. the patient chooses alternative form of treatment Denote by k the number of patients who choose the no treatment option
Higher Program Costs of MFT High cost of maintaining more than one first line treatment Pricing and bargaining power disadvantage with suppliers when buying multiple products from different manufacturers vs. a single product from a single manufacturer Higher cost of training program staff for MFT Managing synchronized procurement cycles for n >1 products is a planning nightmare for already weak procurement systems Buffer/safety stock required to maintain the same level of service in the supply system goes up by a factor of n
Findings from combining choice model, resistance model and higher program costs Let A i = {1, 2,, i} for 1 i n. Then, there exists an S* {A 1,, A n } that maximizes social welfare Theorem 1: k is decreasing in the cardinality of S * Higher variety in the anti-malarial space improves the fraction of those who seek formal treatment Lemma 2: * S A n Social welfare is not maximized by including all available anti-malarials in the treatment assortment for the population. Corollary: A small subset of anti-malarials with very distinct attributes (e.g. single dose, multiple doses) that are farthest from each other on the attribute space should be selected in the socially optimal assortment
Coping with additional costs from MFT Larger volume purchasing from a single supplier does not always lead to lower procurement price for AIDS, TB and Malaria drugs Evidence in Yadav and Lai 2007, What Explains Prices of Pharmaceuticals Purchased by Developing Countries? Similar evidence in Waning et al. 2007 & 2008 Voluntary pooled procurement (VPP) could allow obtaining comparable prices for multiple smaller purchases Procurement systems need to be strengthened to handle synchronized multiple product procurement
Implementing MFT will be a complex multi-stakeholder incentive alignment exercise Donors and National Programs Quality regulators National Programs Prescribers Patients Willingness to share drug switching costs of national programs Willingness to bear additional program costs from increasing choice within the treatment guidelines Expanding the choiceset of qualified and registered suppliers within each therapeutic category requires more human resource capacity at NDRAs Additional program costs for training, monitoring, stock management threadbare treatment guidelines vs. treatment guidelines with more choice Drug switching inertia Or Finding the optimal drug
Conclusions Multiple simulation models show that Multiple First Line Treatments (MFT) delays the emergence and spread of drug resistance MFT also comes with higher program costs, some of which can be reduced MFT could be socially beneficial but only for new products with unique dosing or adherence benefits MFT requires a balanced viewpoint from multi-stakeholders We need studies that closely monitor the emergence and spread of resistance in countries that have recently started MFT to strengthen the evidence base on MFT