Risk and Benefit Analysis Special Lectures

1. RISK BENEFIT ANALYSISSpecial LecturesUniversity of KuwaitRichard WilsonMallinckrodt Professor of PhysicsHarvard UniversityJanuary 13th, 14th and 15th 2002

2. January 15th 2003Decisions about Risks.(1) General Formal ApproachesNet Present Value (NPV)(2) Decision Trees(3) Value Of Information (VOI)Cases:(a) Regulation of PesticidesDaminozide (ALAR) film and write up(b) Control of Particulate Matter(c) Risks of Terrorism

16. Briefing for Acting EPA Administrator(Your Name Here) Background on the Alar Situation January 2003 Richard Wilson based upon an analysis by John Graham and George Gray

17. Alar • Alar is trade name for daminozide - primary manufacturer is Uniroyal Chemical Company • Toxicological concern due to Alar as well as breakdown product and metabolite unsymmetrical dimethylhydrazine (UDMH) • Alar functions as growth regulator - major use is apples • ripe apples stay on tree longer • easier to harvest entire crop at once • improves appearance of apples

18. Pesticide Residue Regulation • EPA registration under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) is necessary for pesticide use • Registration determines which crops pesticide can be used and under what conditions • Use conditions determined to stay within tolerance for that crop • Tolerances set through comparison of efficacy and risk • Stated goal of pesticide regulation is to protect public health while considering the need for "an adequate, wholesome, and economical food supply"

19. Registration Under FIFRA at EPA • Registration is required before a pesticide can be sold or used in the U.S. • Manufacturer must submit efficacy and toxicological data which is used in setting tolerance - burden of proof on manufacturer of pesticide to demonstrate "safety” • Final output of process is legally binding label for the product indicating on which crops, in what amounts, and when it can be used • FIFRA established a Scientific Advisory Panel (SAP) to review EPA's evaluations of pesticide risks to human health and the environment - nonbinding review

20. Reregistration andthe Data Call-in Program • FIFRA 1972 amendments require that all currently registered ("grandfathered") pesticides be reregistered with up to date and modern toxicological data • EPA instituted the Data Call-in Program to get the required toxicity and residue chemistry data to support reregistration

21. Actions Under Reregistration • Continue registration • Request more data • Initiate Special Review process • change terms of registration • cancel some or all uses of pesticide • continue registration as is • Declare imminent hazard and suspend use • In all cases of change in registration the burden in on the Agency to demonstrate "unreasonable risk"

22. Summary of Alar Situation • Alar was first registered in 1963, registration for apples in 1968 • Tolerance for raw apples set at 30 ppm of Alar • 1980 - EPA announces plans for Special Review of Alar in light of Toth et al. animal bioassays - Special review called off after private discussions with Uniroyal (according to Congressional Research Service) • July, 1984 - EPA issues Notice of Initiation of Special Review after litigation by NRDC

23. Summary of Alar Situation • Lowers tolerance from 30 ppm to 20 ppm and sets tolerance expiration date of July 31, 1987 • July 1987 - EPA extends tolerance until January, 1989 • January, 1989 - EPA receives interim report from Uniroyal bioassay - excessive doses and high mortality • January 31, 1989 - extension of tolerance for Alar expires. Uniroyal is asking for another extension until bioassay data complete

24. If I get a disease or accident;What is the Cause?Who do I blame?Who will pay up?How should I change society to protect the next person?

25. Probability of CausationequalsRisk from Substancedivided byRisk from all Causes

26. NRDC's Intolerable Risk Report • Examination of risks of pesticide residues on fruits and vegetables with emphasis on risk to young children • Conclude that preschoolers are "exposed to hazardous levels of pesticides in fruits and vegetables.” • Report singles out UDMH as the "greatest source of cancer risk" in study • "The average preschooler's UDMH exposure during the first six years of life alone is estimated to result in a cancer risk of approximately 1 case for every 4200 preschoolers exposed."

27. Summary of Alar Situation • September, 1985 - EPA sends Draft Preliminary/Final Determination and Draft Cancellation Notice to Science Advisory Panel. SAP determines that scientific data from Toth cancer studies inappropriate for estimation of cancer risk due to excessive doses and high mortality in treated animals • EPA allows continued use of Alar pending new toxicology data from Uniroyal

28. Estimating Risks of Alar • EPA estimate cancer risk due to Alar residues on food at: 4.5 x 10-5 for life time exposure to UDMH 1.5 x 10 -5 during the first 5 years of life assuming a linear dose-response • Remember that we call these "plausible upper limits" to the risk and the risk may be as low as zero • NRDC estimates risk at: 2 x 10-4 during first 5 years of life for average consumers 9 x 10-4 during first 5 years of life for high consumers • NRDC risk estimates ~ 50 times higher than EPA

29. The Questions You Must Face • What factors in addition to the scientific facts must you consider in your decision-making concerning ALAR? • Should you appear on 60 Minutes? Should you reveal the regulatory decision on 60 Minutes? • If you agree to the interview how should you prepare? • In addition to "Why hasn't EPA banned Alar?" and "Is the current law adequate to protect the public from the risks of pesticides?" what other questions should you anticipate?

31. Probability of CausationOld ProcedureCome let us Cast Lots to find out for whose cause this evil is upon us.Jonah 1:7

32. How should I assign POC?Blame?Compensation?Precautionary Regulation?These should be kept distinct

34. Risk from postulated cause is often calculated Risk from all causes can be approximated as the Incidence in a similar population.If the cancer is rare, POC can be high even if the risk is low.

35. POC for berylliosis is unity for beryllium as a causebecause no other cause is knownPOC for asbestos exposure as a cause of mesothelioma among males is 80% (Occupation)and 20% among females

36. Compensation for Radiation Exposures1985 veteran “Downwinders”(if upper 99th percentile of POC > 50%; effectively POC >5%)1996 UK Workers(if POC >20%)2000 Old AEC employees(if upper 99th percentile of POC > 50%; effectively POC >5%)

37. Legal rule to avoid frivolous lawsuits:The postulated cause must be “more likely than not”POC>50% or (RR>2)But Rutherford instructionIf total asbestos exposure is a proven cause, it can be assigned to individual suppliers even if individual POC < 50%.

38. RISK of respiratory ailments due toLIFETIME exposure toAIR POLLUTIONis 3% to 5%average in the USA!POCvaries from30% to 80%Do we compensate?

39. Rule to avoid frivolous lawsuits:The postulated cause must be “more likely than not” POC>50%But Rutherford instructionIf total asbestos exposure is a proven cause, it can be assigned to individual suppliers even if POC < 50%.

40. If I develop leukemia:POC from my Medical Exposureswould be over 50%Could I sue using the Rutherford case?Minister of Health, UKUS State Department (visa requirement)Harvard UniversityCommonwealth of MassachussetsONRDOE (AEC)

41. Value of Information (VOI) AnalysisA Tool for Considering Research Priorities:Are fine particles bad for your health? Richard Wilson, D. Phil., MA Harvard University part of Lecture at the University of Kuwait 13th January 2003

42. John Evans, Sc.D. John Graham, Ph.D. James Hammitt, Ph.D. T.J. Carrothers, Sc.D. Scott Wolff, Sc.D. Jonathon Levy, Sc.D. Jouni Tuomisto, MD, Ph.D. Andrew Wilson, S.M. Joshua Cohen, Ph.D. Example: Risks from PMCase studied in detail by: Research funded by US Environmental Protection Agency ORD as an element of Harvard PM Research Center and also by unrestricted HCRA funds.

43. Basic Framing of Issue • Decisions about environmental control are frequently complicated by uncertainty. • In many cases uncertainty could be reduced by further research. • Decision makers face the tension between acting now or delaying control decisions while research is conducted. • VOI analysis offers a framework for systematic examination of this issue.

45. Hypothetical Problem • In the absence of further control, current levels of exposure to a contaminant leads to population risk, R=1 (cases/yr). We assign $1 million to each case • There are three things which can be done • no control - no cost and no risk reduction • moderate control - 0.25 M $/yr and 50% risk reduction • stringent control - 0.81 M $/yr and 90% risk reduction • Decision criterion is maximization of net benefits (or minimization of total social costs).

46. Total Social Costs(with no uncertainty)

47. Total Social Costas a Function of Unknown Risk

48. Uncertain Estimate of Risk

49. Opportunity Loss • The opportunity loss is the difference between … • the total social cost of the strategy that was chosen on the basis of the expected value of risk, and • the total social cost of the strategy that would have been chosen if the true value of risk had been known before the decision was made.

50. Total Social Costwith Uncertainty in R