Estimating the costs of early infant male circumcision in Zimbabwe: results from a comparative trial of AccuCirc and Mogen Clamp Karin HAtzOld , MD, MPH Population Services International Collin Mangenah, CeSSHAR Zimbabwe Harsha Thirumurthy, UNC 8th International AIDS Economics Network Pre-Conference Meeting July 19, 2014 Melbourne, Australia Good Afternoon Everyone, I will be presenting data on costing of early infant male circumcision, results from a comparative trial of two devices, the Mogen clamp and the AccuCirc device. I would like to acknowledge my two colleagues, Collin Mangenah from Cesshar Zimbabwe and Harsha Thirumurthy from University of North Carolina, who conducted this costing study. Harsha Thirumurthy, University of North Carolina at Chapel Hill Collin Mangenah, Centre for Sexual Health HIV AIDS Research Zimbabwe

Study Background EIMC is cheaper, quicker, simpler & has complete healing in less than 7 days with low rate of AEs Zimbabwe plans to offer EIMC for HIV prevention alongside adult and adolescent VMMC Currently EIMC devices prequalified by WHO New device - AccuCirc pre-packaged, disposable, potentially usable by midwives AccuCirc previously evaluated in Botswana, (single-arm study with 151 male infants) While countries in Southern and Eastern Africa are scaling up Voluntary Medical Male Circumcision for HIV prevention targeting adults and adolescents, several countries have started thinking about the sustainability phase of VMMC and started with pilots in early infant male circumcision. The Zimbabwean Government plans to offer EIMC for HIV prevention alongside VMMC and initiated a pilot implementation study in collaboration with PSI, CESSHAR, UCL and other research partners in Zimbabwe. There are several devices for EIMC that are FDA approved and in use in the US and several other countries conducting EIMC, the most commonly used are the GOMco clamp, the Plastibel procedure and the Mogen clamp. In Zimbabwe we assessed the safety, feasibility, acceptability and costs of a newer device, AccuCirc device, which is going for prequalification by the WHO TAG in September this year. The accuCirc device has been previously evaluated in Botswana in a single arm study with 151 participants. The device comes pre-packaged, pre-sterilised as an disposable instrument set and is potentially to be used by non-physician providers at the primary health care level because of its ease and its safety. Gomco clamp, Mogen clamp & Plastibell (Potential for rare, serious complications2 e.g laceration, amputation or necrosis of the glans penis) Potential EIMC device complications (i) A mismatch in sizes of the separate pieces of the Gomco clamp can result in laceration of the glans penis (ii) circumcision using the Mogen clamp can result in partial or total amputation of the glans penis or removal of too little foreskin (in which case the remaining foreskin remains vulnerable to infection with HIV) (iii) migration of the Plastibell during circumcision can result in necrosis of the glans and other injuries

Prequalification studies in Zimbabwe Comparative trial AccuCirc vs Mogen Clamp Doctor delivered n = 150 Ratio=2:1 Primary outcomes Relative safety Relative acceptability Relative cost Field trial AccuCirc only Nurse mid-wife delivered n=500 No randomisation Primary outcomes Safety Acceptability Cost A Quick overview of the two studies that had been conducted in Zimbabwe with guidance from the WHO TAG in view of the prequalification of the device. The first study was a comparison trial with 150 infants, completed in July last year with 50 mogen clamp circumcision against 100 AccuCirc, the seconfd study was a field trial with 500 AccuCirc device male circumcision for which recruitment has just been finalised. Prmary outcomeswere safety, acceptability and cost.

Costing research questions What is the unit cost of EIMC in Zimbabwe? AccuCirc Mogen Clamp What are the key cost drivers for EIMC in Zimbabwe? Role of various components: Device and Commodities price Personnel salaries Facility capacity utilization Nurse mid-wives procedure time The research question for the costing component was: What is the unit cost of EIMC using either the AccuCirc device or the Mogen clamp and what are the key drivers of its costs, we did a sensitivity analysis of the various cost components: For clinic equipment the purchase price of each capital good was divided by the amortization period to get its annualized depreciation value and multiplied by a discount rate of 3%.

EIMC comparative trial: safety and acceptability results 150 eligible male infants enrolled 100 Accucirc, 50 Mogen clamp 2 moderate (and quickly resolved) adverse events in the AccuCirc arm (95% CI 0.004-0.077) and 0 in the Mogen clamp arm (95% CI 0.0-0.089) Nearly all parents (99.5%) reported great satisfaction with the outcome All parents, regardless of arm said they would recommend EIMC to other parents, and would circumcise their next newborn son Just a quick overview of the results from the safety and acceptability results from the comparative trial, here depicted are the two devices, above the disposable device Accucirc, which has specific safety features incorporated, such as a protective shield for the glans and a circular retractable blade. The mogen clamp below is the most commonly used device in EIMC programs in africa, it is the disadavantage of not having a safety shield to protect the glans bearing the risk of distal tip glans amputation. we had two moderate adverse events, one insufficient skin removal and one excessive sking removal which both resolved quicly and without sequalae. In terrm of acceptabiliy,

EIMC Costing Methods Unit costs Direct (personnel, drugs, supplies, training & environmental costs ) + indirect (capital & overheads) Time and motion to calculate labor costs Stopwatch & video camera captured time spent on each task One way sensitivity analysis Device price, Salaries, Site Capacity Utilization, Procedure time Analysis excludes Costs to clients (transport, caregiver costs) Demand creation costs The Primary outcome of this cost analysis was the monetary cost of equipment, training and labour per EIMC procedure performed. For the costing methods we included unit costs of direct costs, salaries of the different cadres, training unit costs of drugs, supplies, waste management cost, cost for sterilisation of equipment, and indirect costs, capital costs and overheads. For clinic equipment the purchase price of each capital good was divided by the amortization period to get its annualized depreciation value which was multiplied by a discount rate of 3%. %. Its contribution to the unit cost of an EIMC procedure was then calculated by summing the annualized depreciation costs and divided by the total estimated annual number of EIMC procedures. Training costs for the pilot study were allocated over a 3.6 year period in-order to establish the annual training costs. We measured the time of each step involved with the circumcision to calculate labour costs. Uncomplicated EIMC procedures required five visits, comprising a screening visit (visit 1), an EIMC procedure visit (visit 2), follow-up visit day 2, follow-up visit day 7 and follow-up visit day 14. A one way sensitivity analysis was done to appreciate the influence of key drivers The analysis excluded the cost to clients and demand creation costs

Key assumptions Personnel 100% dedicated to EIMC Personnel Salaries based on PSI/Z & CeSHHAR scales Costs collected under pilot field study environment Use of MoHCC perspective excludes costs to clients, care giving costs Analysis based on 3024 annual procedures based on site capacity (12 procedures/day x 252 working days) Doctors trained by international consultants; nurses / mid-wives trained by local master trainers AccuCirc device price = $10 (Clinical Innovations)

Comparative trial costing results Cost Category - direct AccuCirc Cost($)/ EIMC Mogen Clamp Cost($)/EIMC Consumable supplies $15.01 $32.05 Non-consumable supplies $0.27 $0.10 Device cost $10.00 $0.21 Personnel costs $17.13 Training costs $1.88 Environmental costs $1.80 $1.20 Subtotal $46.09 $52.57 Cost Category - indirect Capital equipment costs $0.04 $0.06 Support personnel costs $5.50 $5.54 $5.56 TOTAL UNIT COST OF EIMC $51.62 $58.13 Key cost drivers Consumable supplies Mogen Clamp $32.05/ circumcision vs AccuCirc $15.01/circumcision The Mogen Clamp is a re-usable device 1 which requires sterilisation after every procedure whilst the AccuCirc is a single use (disposable) & self contained kit Personnel costs Personnel costs are based on the salary scales of CeSHHAR Zimbabwe and PSI Zimbabwe. Civil service salary scales are used in sensitivity analysis Mogen Clamp $17.13/ circumcision vs AccuCirc $17.13/circumcision Device costs Price of AccuCirc device ($10) is based on a quotation from Clinical innovations whilst price of Mogen Clamp ($213.23) is based on quotation from SKLAR Instruments All costs in 2013 US$

Cost Comparison of Comparative Trial and Field study** Cost Category - direct Doctor Cost($)/ EIMC Nurse / mid-wife Cost($)/EIMC Consumable supplies $15.01 Non-consumable $0.27 Device cost $10.00 Personnel costs $17.13 $4.68 Training costs $1.88 $0.95 Environmental costs $1.80 Subtotal $46.09 $32.71 Cost Category - indirect Capital equipment costs $0.04 Support personnel costs $5.50 $5.54 TOTAL UNIT COST OF EIMC $51.62 $38.25 Costs for AccuCirc in Comparative Trial (Doctors) vs Field study (Nurses) All costs in 2013 US$ ** Based on 400 EIMCs delivered by nurse/midwife

One way sensitivity analysis Percent change AccuCirc Price Personnel Salaries Site capacity utilization Procedure duration 30% $41.24 $39.65 $36.74 $39.45 20% $40.24 $39.18 $37.16 $39.05 10% $39.24 $38.71 $37.65 $38.65 Base case $38.25 -10% $37.24 $37.78 $38.96 $37.84 -20% $36.24 $37.31 $39.86 $37.44 One way sensitivity analysis of EIMC using AccuCirc & nurse mid-wives Sensitivity analysis confirms device price, personnel costs & site capacity utilization as major cost contributers. Device price In sensitivity analysis AccuCirc unit cost increases with increased device price. A 30% increase in the price of the AccuCirc for example will lead to an increase in the unit cost of an EIMC procedure to $41.24. The anticipated higher price of the AccuCirc for scale-up as indicated by Clinicial Innovations the supplier of the AccuCirc will definitely have a significant impact on the unit cost of the procedure. In fact at the quoted future price of $25 the procedure using the AccuCirc and provided by nurses will cost $53.24 vs $38.25 Personnel costs This analysis utilised actual research staff salaries which are higher than those prevailing in the civil service through which EIMC will be scaled up. Salary scales for local authorities through whose facilities EIMC possibly could be offered in both urban and rural areas are actually higher than those paid to EIMC research staff. In sensitivity analysis decreasing personnel salaries by 20% leads to an decrease in the unit cost of a procedure to $37.31 Site capacity utilization Site capacity at the beginning of the EIMC pilot study was estimated at 12 procedures per day (based on personnel mix and type). However throughout the study challenges were experienced in recruitment leading to much lower numbers of infants circumcised per day. In sensitivity analysis a 30% increase in site capacity utilization for example decreases the unit cost of a procedure to $36.74 Procedure duration In sensitivity analysis reduced procedure time decreases cost of procedure. However improvements in procedure duration by nurses does not lead to substantial cost reductions

Field study cost results cont’d Total cost of EIMC procedure $38.25 by midwives vs $51.62 by doctors Would improvements by nurse mid-wives in time taken to perform a procedure impact the cost? Improvement in time taken by nurse mid-wives on EIMC procedure leads to further reductions in the cost of an EIMC but by a small amount.

Conclusions EIMC using AccuCirc is cheaper compared to Mogen Clamp ($51.62 vs $58.13) Nurse-delivered EIMC is considerably cheaper than by doctors ($38.25 vs $51.62) Key cost drivers are device price, personnel costs, & site capacity utilization Sensitivity analysis confirms device price, personnel costs & site capacity utilization as key cost drivers Improvements in time taken to perform EIMC does not lead to substantial cost reductions ($38.25 vs $ 37.44)

Recommendations Device price is a large portion of AccuCirc costs; Need to negotiate price reduction Site capacity utilization is an important cost driver; Ensuring demand for EIMC is therefore critical Cost substantially reduced if EIMC is performed by nurse mid-wives instead of doctors (this is also likely to make procedure more widely available)

Acknowledgements Centre for Sexual Health & HIV/AIDS Research (CeSHHAR) Zimbabwe, Harare, Zimbabwe Centre for Sexual Health & HIV Research, University College London, London, UK Ministry of Health and Child Care, Harare, Zimbabwe Population Services International-Zimbabwe, Harare, Zimbabwe University of Zimbabwe, Harare, Zimbabwe London School of Hygiene & Tropical Medicine, London, UK UNC Gillings School of Global Public Health, NC, USA Bill & Melinda Gates Foundation, USA City Health Department, Harare, Zimbabwe EIMC Study team Gerald Gwinji, MoH Zimbabwe Getrude Ncube, MoH Zimbabwe Owen Mugurungi, MoH Zimbabwe Cynthia Chasokela, MoH Zimbabwe Margaret Nyandoro , MoH Zimbabwe Nontando Mothobi, MoH Zimbabwe Ismail Ticklay, University of Zimbabwe Karin Hatzold, Population Services International Christopher Samkange, University of Zimbabwe Collin Mangenah, CeSSHAR; Frances Cowan, CeSHHAR; University College London Judith Sherman, UNICEF Zimbabwe Webster Mavhu, CeSHHAR; University College London Helen Weiss, London School of Hygiene & Tropical Medicine Harsha Thirumurthy, University of North Carolina at Chapel Hill Andrea Biddle, University of North Carolina at Chapel Hill