1. COSTS STUDY OF SEVERE PNEUMONIA IN AN EQUIVALENCE TRIAL OF ORAL AMOXICILLIN VERSUS INJECTABLE PENICILLIN IN CHILDREN AGED 3 TO 59 MONTHS Patel AB, APPIS Trial group, Indira Gandhi Medical College, Nagpur, India. Source of Funding: Department of Child and Adolescent Health and Development, World Health Organization; Applied Research in Child Health (ARCH) Project and USAID grant

2. Injectable penicillin is the recommended treatment for WHO-defined severe pneumonia [lower chest in-drawing (LCI)] Oral amoxicillin, if found equally effective, could reduce referral, hospitalization, the risk of needle-borne infection, administration costs and costs to family. INTRODUCTION

3. This multicentre randomized, open label equivalency study - APPIS (Amoxicillin Penicillin Pneumonia International Study) was conducted at tertiary care centres in 8 countries. Costs of treating severe pneumonia was estimated at Nagpur center in India.

4. OBJECTIVES To determine the total costs, direct medical, direct non-medical and indirect costs of treating severe pneumonia in a tertiary care hospital within an equivalence trial of parenteral penicillin and oral amoxicillin in children aged 3-59 months

5. METHODS Central randomisation at WHO. Envelopes opened in their allocation sequence. Baseline characteristics assessed Assignment to either oral amoxicillin syrup (45mg/kg/day divided in three doses) or parenteral penicillin G (200,000 IU/kg/day divided in four doses) for 48 hours.

6. METHODS If better (absence of LCI with fast breathing) discharged at 48 hours with a course of oral amoxicillin for 5 days Outcome assessment periods - 48 hours, 5th day and 14 th day

7. Definitions of Treatment Failures (Outcome) 48 hrs - Persistence of lower chest in-drawing -- - Low oxygen saturation - Appearance of danger signs - Life-threatening or serious adverse drug reaction - Received another antibiotic - Newly diagnosed co-morbid condition - Parents/guardian withdrew consent - Child left against medical advice - Death

8. DEFINITION OF TREATMENT FAILURES (Outcomes) 5th day - Previously defined as treatment failure at 48 hours - Recurrence of lower chest wall in-drawing 14th day - Previously defined as treatment failure at 48 hours or 5th day - Signs of non-severe pneumonia on follow-up at 14th day

9. RESULTS - STUDY EFFICACY Treatment failures 48 hours - 19% in each group (risk difference - 0.4; 95% CI -4.2 to 3.3) 5th day - 22% cumulative 14 th day - 25% Baseline characteristics were similar in both groups

10. CategoriesTime Period Direct MedicalBefore Enrolment(BE) Direct Non-Medical Hospitalization(Hosp) IndirectVisits Perspective – Family and Government Protocol driven costs were excluded COST ASSESSMENTS

11. RESULTS - Direct Medical Costs BE 12.37 (±44.22) 9.90 (±25.05) 0.62 Hosp 728.68 (±256.73) 838.05 (±410.80) 0.02 Visits 47.03 (±22.12) 47.94 (±26.76) 0.80 Services 296.4 (±107.25) 236.74 (±117.35) 0.65 Investigations 358.46 (±27.54) 375.14 (±129.61) 0.20 Medication 114.40 (±113.79) 216.32 (±207.76) 0.0001 Overall 788.09 (±260.47) 895.40 (±396.88) 0.02 Costs Amoxycillin Penicillin P [Mean (±S.D.)] [Mean (±S.D.)] Value

12. RESULTS - Direct Non-Medical Costs BE 0.68 (±3.83) 1.47 (±6.98) 0.3 Hosp 51.48 (±54.61) 54.10 (±48.61) 0.7 Visits 16.58 (±20.90) 18.57 (±26.34) 0.5 Overall 68.74 (65.73) 73.6 (±67.72) 0.5 Costs Amoxicillin Penicillin P [ Mean (±S.D.)] [ Mean (±S.D.)] Value

13. RESULTS - Indirect Costs Hosp 41.9(±46.7) 41.7 (±62.3) 0.7 Visits 11.9 (±22.1) 3.1 (±6.7) 0.03 Total 54.4 (±83.2) 43.9 (±61.8) 0.27 Costs Amoxicillin Penicillin P Value [ Mean (±S.D.)] [ Mean (±S.D.)]

14. Average Daily 307 (±50.7) 373 (±147) 0.006 Medical Cost RESULTS - Total Costs Before Enrolment 13.05 (±44.77) 11.37 (±30.45) 0.7 Hospitalization 834.40 (±335.18) 921.51 (±445.26) 0.05 Visits 74.25 (±41.56) 73.51 (±42.22) 0.90 Total Cost 920.13 (±344.05) 1004.65 (±432.64) 0.06 Costs Amoxicillin Penicillin P [ Mean (±S.D.)] [ Mean (±S.D.)] Value

15. RESULTS - COSTS SAVINGS Prevalence of severe pneumonia is estimated to be 6 % (6 M ) in under-five At least 30 % (257142)would be treated according to the national program with inj. penicillin Incidence estimated to be 857142 per year Cost-saving of Rs.110 per case would annually save Rs.28.3 M

16. LIMITATIONS Unmeasured protocol driven costs can inflate costs of treatment. Variability in determining resources and costs use limits generalizability of study. Cost savings have been underestimated, as oral treatment if given at home can further reduce loss of wages to family ( Indirect cost). Decision tree needed to estimate projected cost savings due to prevention of needle bourne infections / or morbidity/ or mortality due to oral amoxicillin

17. CONCLUSIONS Amoxicillin was clinical equivalent to injectable penicillin in the treatment of severe pneumonia At the health care facility cost saving was Rs.110 per case Additional research is needed to estimate the full public health and costs benefit at the community or household level