evalua&ng)evidence) - university of california,...
TRANSCRIPT
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1. The Se,ng
2. A Story 3. The goal and why it’s so hard to reach
4. Tools for taking ac?on despite uncertainty 5. What would you do?
Evalua&ng Evidence Making Decisions in Uncertain Condi?ons
Meg Schwarzman Green Chemistry -‐-‐ 234 April 6, 2011
1. The Se,ng Pace and scale of technological advancement vs. capacity to assess impacts
72 billion lbs/day
Toys Cleaners Food Furniture Clothing Building materials Personal care products Electronics
CDC found 212 substances in the 2003-‐04 NHANES par?cipants -‐-‐ 163 in pregnant women
Synthe?c Chemicals are Ubiquitous
First 15 years of TSCA: EPA reviewed the risks of 2% of 62,000 exis?ng chemicals vs. es?mated 26% of concern. (GAO 1994)
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1. The Se,ng How Should we Respond?
Diagram drawn during lecture depic?ng the range of responses to the problems associated with chemicals, introducing the need to make decisions in the face of uncertainty. See video for details.
2. A Story
September 5th, 2008!
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UNPUBLISHED!
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>>> 8/21/2009 12:02 PM >>> Matthew Neff wrote: Dr. Schwarzman, Our medical editor, Kenny Lin, decided to reject the letter from Dr. Witorsch (and by default your response) due to potential author bias related to Dr. Witorsch's connections to the chemical industry. I apologize that these were not discovered before I solicited a response from you. I do appreciate your taking the time to write a reply.
Regards, Matthew Neff Senior Editor, American Family Physician
>>> Megan Schwarzman <[email protected]> 8/21/2009 1:58 PM >>>
It strikes me that -‐-‐with full disclosure of Dr. Witorsch's affilia?ons-‐-‐ publica?on of his leier and my response could be of great value. The transparency is of course cri?cal. A straighjorward demonstra?on of how the science is frequently misconstrued would be a real contribu?on the Journal could make, par?cularly for clinicians who are not steeped in the literature of this topic.
I'd be interested whether the medical editor would consider this.
Many thanks, Megan
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>>> Megan Schwarzman <[email protected]> 12/4/2009 7:38 PM >>> Dear Dr. Neff,
Thanks for sending along the leier from Dr. Kamrin. Although Kamrin did not claim any conflicts of interest, a brief Google search and scan of the literature uncovers a porjolio of affilia?ons fairly similar to Dr. Witorsch's. Kamrin is a re?red toxicologist from Michigan State University who has asserted, among other things, that dioxins are not a health hazard (specifically, TCDD, which is the most potent carcinogen known). An ar?cle ?tled "On the Dole of Dow" (starts on p. 7 of the aiached newsleier) describes some of this, as well as Michigan State's COI given their longstanding links with Dow. Kamrin's role is detailed star?ng on p. 12. The key ar?cle that Kamrin cites in his leier against low dose science is his own (note the quota?on marks in the ?tle): Kamrin MA. The "low dose" hypothesis: validity and implica?ons for human risk. Int J Toxicol. 2007;26(1):13-‐23.hip://ijt.sagepub.com/cgi/reprint/26/1/13
That ar?cle was funded by the "American Council on Science and Health" (on whose board of scien?fic advisers Kamrin serves) hip://www.acsh.org/ Here's an excerpt about the ACSH from the aiached newsleier ar?cle on Dow: "ACSH has argued that cholesterol is not linked to heart disease, irradia?on of food is fine, and saccharin is not carcinogenic. In 1997 an ACSH study concluded that childhood lead poisoning is no longer a widespread public health threat. Dow Chemical has funded the ACSH in the past though their current list of funding sources is secret."
Kamrin's wri?ngs are featured on the ACSH website, which also highlights a recent editorial from Investor's Business Daily calling Lisa Jackson (EPA's head Administrator) an "ideologue... unscien?fic radical ac?vist.“ ACSH also paid for Kamrin's recent ar?cle that is a revisionist review of phthalate toxicity, which concludes with the standard chemical industry statement: "there is no convincing evidence of adverse effects [of phthalates] on humans. Since the scien?fic evidence strongly suggests that risks to humans are low, phthalate regula?ons that have been enacted are unlikely to lead to any marked improvement in public health." hip://pdfserve.informaworld.com/295143_731350710_908974039.pdf
If you plan to publish Kamrin's leier, I will of course write a response. But, as before with Dr. Witorsch's leier, I would reveal the obvious conflicts of interest posed by his longstanding industry affilia?ons and espousal of their views. I'd like not to invest the ?me, however, if your editor feels Kamrin's conflicts will preclude publica?on. In case it's of interest, I'm also aiaching our recent piece on EDCs published in last week's edi?on of Science Magazine.
Regards, Megan
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-‐-‐-‐-‐-‐-‐-‐-‐ Original Message -‐-‐-‐-‐-‐-‐-‐-‐ Subject: Re: Letter to the Editor of AFP Regarding your Editorial Date: Sat, 05 Dec 2009 09:54:07 -‐0600 From: Matthew Neff [email protected] To: Megan Schwarzman <[email protected]>
Dr. Scwarzman, Thank you very much for brining all of this to our attention. I will forward this on to our medical editor and we will review. I will let you know if we decide to reject the letter based on this information or decide to go ahead with publication. Thanks again.
Matthew Neff Senior Editor American Family Physician 11400 Tomahawk Creek Pkwy Leawood, KS 66211-‐6272
The End
3. The goal and why it’s so hard to reach
Risk = ƒ (hazard, vulnerability, exposure)
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Risk, Uncertainty, and Ignorance
EEA. 2001. Late Lessons from Early Warnings: The Precau?onary Principle 1896-‐2000. Environment Issue Report, no. 22. (Harremoes P, Gee D, MacGarvin M, S?rling A, Keys J, Wynne B, et al., eds). Copenhagen: European Environment Agency.
Risk Assessment Challenge 1: Hazard Iden?fica?on
Hazards differ by life stage Gesta?onal exposures affect developing organ systems Effects oxen not manifest un?l decades later Epigene?cs: gene expression changes can span genera?ons
Uncertainty and ignorance make it hard to ask the right ques?on
Tes?ng for the most sensi?ve endpoint Control vs. prenatal exposure to DES at 1ppb High dose causes decreased birth weight Low dose causes obesity
Newbold et al. Env. Health Perspet. v.113, 2005.
DES treated prenatally. Puberty-‐onset obesity
Control
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Risk Assessment Challenge 2: Dose-‐Response
Welshons et al. Environmental Health Perspec8ves 111:8 (2003)
Extrapola?on from high to low doses can mischaracterize effects
Ability to Establish “Proof” Depends on Level of Evidence Required
Choosing the right endpoint Lack of controls – ubiquitous exposure Mixed exposures – addi?ve effects Extrapola?on from animal tests: acute
vs. chronic; mixed exposures Industry influence – manufacturing
doubt
Levels of Evidence Complica?ng Factors
Proof of cause-‐and-‐effect
Balance of the evidence
Reasonable grounds for concern
Scien?fic suspicion of risk
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Associa?on of Urinary BPA Concentra?on With Medical
Disorders and Laboratory Abnormali?es in Adults Lang et al. JAMA, Sept 17, 2008—Vol 300, No.11
“Overall the new study, because of the inherent study design, cannot support the conclusion that BPA causes any disease. This kind of a study is inherently incapable of developing a cause-‐and-‐effect rela?onship.”
“Our view is that the science s?ll con?nues to support the safety of products made from bisphenol A. We have not seen the weight of the evidence shixing apprecia?vely [sic].”
Steve Hentges, American Chemistry Council polycarbonate/BPA Global Group
Epidemiology Can’t Prove Causa?on
Good Laboratory Prac?ces (GLP) Really?
GLP Does: Govern private labs tes?ng chemicals for regulatory purposes (not subject to IRB, peer review) Apply to care of animals, facili?es, equipment, and data collec?on
GLP Does Not: Govern government or academic research Address study design, personnel skills, or quality of test methods
Myers et al., Environmental Health Perspec?ves, 2008
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What GLP Studies Missed (BPA)
Endpoints found by independent research; not inves?gated by GLP studies:
Metabolic regula?on (insulin and adiponec?n) Prostate and mammary gland development
Reproduc?ve anomalies (fibroids, cysts, chromosomal abnormali?es in oocytes)
Brain and behavior changes
Outcomes Differ by Study Funding Source
Flaws in some industry-‐funded science Lack of posi?ve controls; Insensi?ve species Estrogenic feed Non-‐standard study methods Evalua?ng less-‐sensi?ve endpoints
Vom Saal and Welshons, Environmental Health Perspec?ves, 2006
Review of 109 Low-‐dose BPA studies; No Industry-‐funded studies showed harm
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Early Warnings for Mercury Toxicity Regulatory Thresholds Decline with New Science
Scheiler T, et al. Physicians for Social Responsibility, 2002
Cholera Epidemic of 1854, Broad Street District, London
Service area of the Broad Street well.
Primary preven?on: Remove the handle
4. Tools for taking ac?on in face of uncertainty
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Minimizing the Impact of Ignorance
Limit scope of possible surprises • Diversify technologies • Consider intrinsic proper?es • Minimize overall use of energy and materials • Account for real-‐world scenarios
Generate (and make good use of) informa?on • Monitor for possible impacts • Inves?gate all alterna?ves • Examine claims of efficacy and benefit • Seek interdisciplinary input, both scien?fic and local
5. What Would You Do?
Lex blank for in-‐class discussion of homework assignment.