Sensitivity analysis We used the technique of Probabilistic Sensitivity Analysis (PSA) to account for uncertainty in the model input parameters. PSA lets uncertainty in the input parameters be reflected in the model output (the ICER). We identified and addressed the following sources of uncertainty in our base-case ICER estimate: the uncertainty around the relative risk values [35], the values of screening uptake [15], the sensitivity and specificity of the screening instrument [12], the follow-up rate of the brief intervention [10], decrease in alcohol consumption [10], and, the fraction of decrease in alcohol consumption maintained in the long run [22,23,24]. Table 4 summarizes the assumptions and the distributions for the input parameters used in the different References 1. Ezzati M, Lopez AD, Rodgers A, Van der Hoorn S, Murray CJ (2002) Selected major risk factors and global and regional burden of disease. Lancet 360(9343): 1347–1360. 2. Room R, Babor T, Rehm J (2005) Alcohol and public health. Lancet 365(9458): 519–530. 3. Cnossen S (2007) Alcohol taxation and regulation in the European Union. International Tax and Public Finance 14(6): 699–732. 4. Saitz R (2005) Unhealthy alcohol use. N Engl J Med 352: 596–607. 5. de Hollander AEM, Hoeymans N, Melse JM, van Oers JAM, Polder JJ (2007) Care for health. The 2006 Dutch Public Health Status and Forecasts Report. Bilthoven. 6. CBS Statline, 2007 Statistics Netherlands. 7. Fleming MF, Barry KL, Manwell LB, Johnson K, London R (1997) Brief physician advice for problem alcohol drinkers. A randomized controlled trial in community-based primary care practices. JAMA 277: 1039–1045. 8. Fleming MF, Manwell LB, Barry KL, Adams W, Stauffacher EA (1999) Brief physician advice for alcohol problems in older adults. A randomized community-based trial. J Fam Pract 48(5): 378–384. 9. Senft RA, Polen MR, Freeborn DK, Hollis JF (1997) Brief intervention in a primary care setting for hazardous drinkers. Am J Prev Med 13: 464–470. 10. Bertholet N, Daeppen JB, Wietlisbach V, Fleming M, Burnard B (2005) Reduction of alcohol consumption by brief alcohol intervention in primary care. Systematic review and meta-analysis. Arch Intern Med 165: 986–995. 11. Beich A, Thorsen T, Rollnick S (2003) Screening in brief intervention trials targeting excessive drinkers in general practice: systematic review and meta- analysis. BMJ 327: 536–542. 12. Fiellin DA, Reid MC, O’Connor PG (2000) Screening for alcohol problems in primary care. A systematic review. Arch Intern Med 160: 1977–1989. 13. Bray JW, Zarkin GA, Davis KL, Mitra D, Higgins-Biddle JC, et al. (2007) The effect of screening and brief intervention for risky drinking on health care utilization in managed care organizations. Med Care 45: 177–182. 14. Drummond MF, Sculpher MJ, Torrance GW, Stoddart GL (2005) Methods for the economic evaluation of health care programmes. Third edition edition. Oxford: Oxford University Press. 15. Solberg LI, Maciosek MV, Edwards NM (2008) Primary care intervention to reduce alcohol misuse. Ranking its health impact and cost effectiveness. Am J Prev Med 34(2): 143–152. 16. Wutzke SE, Shiell A, Gomel MK, Conigrave KM (2001) Cost effectiveness of brief interventions for reducing alcohol consumption. Social Science and Medicine 52: 863–870. 17. Babor TF, Higgins-Biddle JC, Dauser D, Burleson JA, Zarkin GA, et al. (2006) Brief interventions for at-risk drinking: patient outcomes and cost-effectiveness in managed care organizations. Alcohol & Alcoholism 41(6): 624–631. 18. Kraemer KL (2007) The cost-effectiveness and cost-benefit of screening and brief intervention for unhealthy alcohol use in medical settings. Substance Abuse 28(3): 67–77. 19. Fleming MF, Mundt MP, French MT, Manwell LB, Stauffacher EA, et al. (2000) Benefit-Cost Analysis of brief physician advice with problem drinkers in primary care settings. Medical Care 38(1): 7–18. 20. Fenwick E, Claxton K, Sculpher M (2007) Respresenting uncertainty: the role of cost-effectiveness acceptability curves. Health Econ 10: 779–787. 21. Van Baal PHM, Van den Berg M, Hoogenveen RT, Vijgen SMC, Engelfriet PM (2008) Cost-effectiveness of a low-calorie diet and orlistat for obese persons: Modeling long-term health gains through prevention of obesity-related chronic diseases. Value in Health 11(7): 1033–1040. 22. Babor TF, McRee BG, Kassebaum PA, Grimaldi PL, Ahmed K, et al. (2007) Screening, Brief intervention and referral to treatment (SBIRT): Toward a public health approach to the management of substance abuse. Substance Abuse 28(3): 7–30. 23. Wutzke SE, Conigrave KM, Saunders JB, Hall WD (2001) The long-term effectiveness of brief interventions for unsafe alcohol consumption: a 10-year follow-up. Addiction 97: 665–675. Excessive Alcohol Use scenarios. In order to perform the analysis the model was run 1000 times. For each run of the model, at random a number is drawn for each of the ‘‘uncertainty’’ parameters from the distribution specified for that parameter (see table 4). This leads to a different output of the model for each run. The variability in outcome is then a reflection of the uncertainty due to the input parameters. Author Contributions Conceived and designed the experiments: MVdB. Performed the experiments: PHMvB. Analyzed the data: LT RTH PHMvB. Wrote the paper: LT MVdB PHMvB. 24. Nilssen O (2004) Long-term effects of brief intervention in at-risk alcohol drinkers: a 9-year follow-up study. Alcohol & Alcoholism 39(6): 548–551. 25. Baumberg B, Anderson P (2006) Alcohol in Europe: a public health perspective. London: Institute of alcohol studies. 26. Schutten M, Jansen H, Meerkerk GJ, Van de Wetering B, Van de Mheen D (2004) Laagdrempelige screening en behandeling van alcoholproblematiek in de huisartspraktijk. Zelfde gang, deurtje verder. Rotterdam: IVO instituut voor onderzoek naar leefwijzen & verslaving. 27. Saunders JB, Aasland OG, Babor TF, De la Fuente J, Grant M (1993) Development of the alcohol use disorders identification test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption. Addiction 88: 791–804. 28. Van Baal PH, Hoogenveen RT, de Wit GA, Boshuizen HC (2006) Estimating health-adjusted life expectancy conditional on risk factors: results for smoking and obesity. Popul Health Metr 4: 14. 29. Jacobs-van der Bruggen MA, Bos G, Bemelmans WJ, Hoogenveen RT, Vijgen SM, et al. (2007) Lifestyle interventions are cost-effective in people with different levels of diabetes risk: results from a modeling study. Diabetes Care 30(1): 128–134. 30. Hoogenveen RT, van Baal PH, Boshuizen HC, Feenstra TL (2008) Dynamic effects of smoking cessation on disease incidence, mortality and quality of life: the role of time since cessation. Cost Eff Resour Alloc 6(1): 1. 31. Van Baal PHM, Polder JJ, De Wit GA, Hoogenveen RT, Feenstra TL, et al. (2008) Lifetime medical costs of obesity. Prevention no cure for increasing health expenditure. PLoS Med 5(2): 242–249. 32. Van Baal PHM, Feenstra TL, Hoogenveen RT, De Wit GA, Brouwer WF (2007) Unrelated medical care in life years gained and the cost utility of primary prevention: in search of a ‘perfect’ cost-utility ratio. Health Econ 16: 421–433. 33. Van den Berg M, van Baal PHM, Tariq L, Schuit JS, de Wit GA, et al. (2008) Modelling the cost-effectiveness of increasing alcohol taxation. BMC Medicine 6: 36. 34. Struijs JN, Van Genugten MLL, Evers SMAA, Ament AJHA, Baan CA, et al. (2005) Modelling the future burden of stroke in The Netherlands. Stroke 36(8): 1648–1655. 35. Holman CD, English DR, Milne E, Winter MG (1996) Meta-analysis of alcohol and all-cause mortality: a validation of NHMRC recommendations. Med J Aust 164(3): 141–145. 36. POLS, gezondheid en arbeid (2006) Permanent Onderzoek Leefsituatie, gezondheid en arbeid (CBS) . 37. Melse JM, Essink-Bot ML, Kramers PGN, Hoeymans N (2000) A national burden of disease calculation: Dutch disability-adjusted life-years. AJPH 90: 1241–1247. 38. Slobbe LCJ, Kommer GJ, Smit JM, Groen J, Meerding WJ, et al. (2003) Cost- of-illness in The Netherlands. Bilthoven. 39. College van Zorgverzekeringen (2005) Richtlijnen voor farmaco-economisch onderzoek; evaluatie en actualisatie. Diemen: CVZ. 40. Bradley KA, Bush KR, McDonell MB, Malone T, Fihn SD (1998) Screening for problem drinking. Comparison of CAGE and AUDIT. J Gen Intern Med 13: 379–388. 41. Bush K, Kivlahan DR, McDonell MB, Fihn SD, Bradley KA (1998) The AUDIT alcohol consumption questions (AUDIT-C). Arch Intern Med 158: 1789–1975. 42. Volk RJ, Steinbauer JR, Cantor SB, Holzer CE (1997) The alcohol use disorders identification test (AUDIT) as a screen for at-risk drinking in primary care patients of different racial/ethnic backgrounds. Addiction 92(2): 197–206. 43. Oostenbrink JB, Bouwmans CAM, Koopmanschap MA, Rutten FFH (2004) Standaard kostprijzen en rekenwaarden. Bijlage bij ‘‘Handboek voor Koste- nonderzoek, methoden en standaard kostprijzen voor economische evaluaties in de gezondheidszorg’’. Diemen: CVZ. 44. Jarl J, Johansson P, Eriksson A, Eriksson M, Gerdtham UG, et al. (2008) The societal cost of alcohol consumption: an estimation of the economic and human cost including health effects in Sweden. Eur J Health Econ 9: 351–360. PLoS ONE | www.plosone.org 7 May 2009 | Volume 4 | Issue 5 | e5696