Presentation to: UNINTENTIONAL DEATH COMMITTEE Discussion of Limiting Youth Exposure to Tanning Beds

Transcription

1 Presentation to: UNINTENTIONAL DEATH COMMITTEE Discussion of Limiting Youth Exposure to Tanning Beds PRESENTATION BY LEE FELDMAN, CHIEF SCIENTIFIC OFFICER INSTITUTE FOR SCIENTIFIC POLICY ANALYSIS TRYON, NC / WASHINGTON, DC ROOM 1027, LEGISLATIVE BUILDING 10:00 23-JANUARY-2012

2 Summary 1 Science Not Advocacy 2 Brief discussion of review of the state of research regarding weakness of correlational and causal linkages between tanning bed exposure and Cutaneous Malignant Melanoma (CMM) 3 Resolution of research findings & conclusions: Is their actionable information indicated in current science findings & conclusions? 4 Applicability of Precautionary Principle to health policy in this instance 2

3 High Integrity Policymaking Quality Input to Policymakers STAKES SOCIAL INTEREST (i) Narratives about the world become Mythologies NAR 0 NAR 1 NAR n Narratives about the world become Mythologies NAR 0 NAR 1 NAR n MYTH 0 MYTH 1 Myth n MYTH 0 MYTH 1 Myth n WARRING MYTHS WARRING MYTHS Ideally, the duration/intensity of the Evidentiary Epoch increases as the stakes get higher Myths yield to facts and analyses High Integrity Policymaking Method Improves Quality and Utility of Evidentiary Epoch Myths are exposed to evidence and evolve into better understandings of reality (sometimes) Myths yield to facts and analyses POLICY POLICY Normal Distortions Reduced Mythological Epoch Evidentiary Epoch Policy Epoch TIME (t) Lee T Feldman,

4 Distortion to Evidentiary Analysis Caused by High Social Interest Narratives about the world become Mythologies STAKES SOCIAL INTEREST (i) NAR 0 NAR 1 NAR n Narratives about the world become Mythologies, BUT NAR 0 NAR 1 NAR n MYTH 0 MYTH 1 Myth n MYTH 0 MYTH 1 Myth n WARRING MYTHS WARRING MYTHS Myths compete to become policy Unfortunately, EVIDENTIARY DEVELOPMENT Often Declines as Social Interest Increases POLICY The facts become a speed-bump as policymakers race forward to make policy POLICY Normal Distorted Mythological Epoch Evidentiary Epoch Policy Epoch TIME (t) Lee T Feldman,

5 Brief discussion of review of the state of research regarding strength of causal linkages between tanning bed exposure and Cutaneous Malignant Melanoma (CMM) 5 There are significant problems with current research exploring the linkage (if any) between indoor tanning bed use (UV-A & UV- B exposure) and cutaneous malignant melanoma Poor study designs, Significant methodological errors Highly subjective recall biases Several important biases in interpreting findings Conclusions that reach beyond the findings and many other problems summarized in Appendix I and the FDA report we have provided to you These studies do not achieve the level of research fidelity needed to be used as a basis for policy-making

6 Other Serious Problems with the Research 6 Studies relating indoor tanning-sourced UV-CMM studies, include coding elements that are substantially subjective: o Recall Bias: Interestingly, but not surprisingly, exposure recall varied between cases (cancer patients) and controls The degree to which this may add uncertainty to the result needsto be further investigated We believe there may be an unavoidable precautionary bias inherent to research in this field o Recall facts where there known significant recall biases: sunburn history (degree& frequency) type of tanning device used exposure durations (any history of tanning bed burn ) age of first exposure first burn level of environmental exposure (regular/episodic), consumer understanding of predisposing risk factors (skin type, moles, family history, etc) and environmental exposures (eg, latitude, indoor/outdoor work environment, etc) that may play a role in their decisions about UV exposure Selection bias in meta analyses: o decision to include or reject a particular study o different ways to measure effects (standardized mean difference or correlation) o diagnostic drift bias related to dysplastic or malignant nevi o the interpretation of effect size is also subjective For example, it is not clear if the IARC and other studies (eg, Lasovich) study employed the most accurate statistical method for combining results (fixed effects model or the random effects model

7 Resolution of research findings & conclusions: Is their actionable information indicated in current science findings & conclusions? Human co-evolution with sunlight suggests that there are complex and multifactorial relationships between biological mechanisms that have evolved: Vitamin D synthesis and by-product metabolites While there are known disease protective differences between oral D3 (supplements) and UV-produced Vitamin D, yet the mechanisms of action are not understood Some argue that supplements are a complete substitute for UV-sourced vitamin D There is no science to back up the claim and compliance is a major challenge Epigenetics (see next slide) 7

8 Unintended Consequences 8 Epigenetics may be an important factor that has not been studied An epigenetic trait is a change in the phenotype (appearance), or gene expression, or a stably inherited phenotype resulting from changes in a chromosome without alterations in the DNA sequence, ie, causedby mechanisms other than changes in the underlying DNA sequence These changes may remain through cell divisions for the remainder of the cell's life and may also last for multiple generations (heritable) Epigenetics may play a significant role in the higher CMM susceptibility of people with infrequent UV exposure compared to people who have greater sustained (occupational) exposures yet lower rates of CMM This would include exposure-related and other environmental factors that may be driving increasing rates of CMM (other than that caused by diagnostic drift) There are three categories of signals that operate in the establishment of a stably heritable epigenetic state: the first is a signal from the environment, the second is a responding signal in the cell that specifies theaffected chromosomal location, and the third is a sustaining signal that perpetuates the chromatin change in subsequent generations

9 Epigenetics (continued) 9 Because humans have an exquisitely complex, evolved set of mechanisms that regulate the response to UV exposure, and these mechanisms incorporate epigenetic components that also regulate near-term heritable traits (eg, skin color which changes more quickly than DNA-regulated evolution allows and is heritable), We may learn that reducing overall non-burninguv exposure has the UNINTENDED CONSEQUENCE of increasing susceptibility to CMM and other disease ie, telling us to reduce burning exposures by staying out of the sun or other UV has the: (known) result of promoting a Vitamin D deficient population and, the (hypothesized) effect of preventing our bodies from mounting an adequate response to normal, non-burning UV exposures

10 Melanoma Risk is Multifactorial Imposing a Burden of Disease Analysis on Melanoma Risk Studies 10 Because CAUSAL factors for CMM risk are complex: A higher standard of evidence is required to move from correlative studies (ie, epidemiological) to conclusions about cause Complex confounders o Sunburn has a correlational association with CMM that rises to the standard needed to presume causation o HOWEVER, Non-Burning UV exposure does not o Other confounders MUST be considered in studies with clear firewalls between sub-groups in epidemiological studies Genetic factors, skin types, etc Environmental factors (UVA vs UVB ratios, etc) Nevi History of burns Other biological confounders (eg, hormonal exposures) Other environmental confounders (latitude, level of background exposure, etc)

11 Where does this leave us? 11 UNINTENDED CONSEQUENCES AND THE PRECAUTIONARY PRINCIPLE

12 Applicability of Precautionary Principle to health policy in this instance Resolution of research findings & conclusions: Is their actionable information indicated in current science findings & conclusions? It seems reasonable to think that: Because burning UV exposure is a known hazard Therefore, non-burning UV exposure is also a hazard o Especially since we seem to have a plausible mechanism of action (DNA cleavage) Therefore, a precautionary approach intending to reduce exposures should also reduce the hazard BUT IT WON T 12

13 Science Siloes and Unintended Consequences that Derive from Precautionary Policies 13 Premise: We assume the goal is absolute harm reduction rather than simply looking to reduce the use of indoor tanning facilities Fact: Given the weaknesses in the studies, it is not at all clear we can conclude that tanning beds impose a meaningful risk of CMM (ie, a risk greater than other normal daily activities that involve non-burning UV -sun- exposures) Obviously, this is disputed, but our read of the research suggests there is no evidence of a causalrelationship Even the correlationalrelationships are only weakly coupled to indoor tanning versus predisposing risk factors which have a higher correlation to CMM An inadequately explored area of research is the relative contribution to risk caused by predisposing risk factors: Prior or family history of CMM History of sun burns Unevaluated dysplastic nevi or many nevi Infrequent regular UV exposure Etc Fact: There are provocative epigenetic hypotheses that reducing controlled UV exposures may increase rates for cancer (esp colon cancer) There is a developing understanding of epigenetic response to UV that may suggest that limiting UV exposure actually reduces our ability to develop an appropriateprotective response when exposures occur

14 Science Siloes and Unintended Consequences that Derive from Precautionary Policies Fact: There are alternatives for tanners if restrictions prevent them from using indoor tanning facilities: Outdoor exposures where there is a known and predictable (and significant) risk of overexposure and burns, especially among adolescents Opinion studies of adolescents and college students clearly showthat knowledge of the risks from sun exposures does not prevent over-exposures and burns even when the study participants are fully cognizant of the risks We are not aware of any studies that have explored how people will respond to restrictions on the availability of salon-tanning --- Will they engage in more risky tanning modalities? Unsupervised home tanning also increases the risk of accidental burns, or tanning by individuals with predisposing risk factors who should not tan at all Fact: Predisposing risk factors are more relevant, and have a much higher correlative signature to CMM than indoor tanning without risk factors Fact: Tanning salons provide an adult-supervised, controlled environment where assessment and control of tanning risks are rigorous (and could be even more rigorous) Identification of, and education about, risk factors about which the consumer may be unaware Regulation of exposure durations and frequency Consumer education about safe UV exposure (outdoor, indoor, at work, etc) Controlled tanning modalities are highly preferable to pushing people into uncontrolled, unsupervised, and unaware outdoor sun exposure (where even FredType I skin types who should never tan, freely go out and get burned) 14

15 Summary findings of our analysis Summary findings of our analysis Two key take-aways: 15 1The current body of research related to indoor tanning and CMM and other cancers is not complete, has too many methodological flaws, has too many inherent biases, does not demonstrate a causal linkage,and is inadequate for use in a policy-making context 2Dermatologists are correctly practiced in the dictum when in doubt, take it out However, in this case, a precautionary approach has a serious side effect: Taking out controlled tanning modalities (eg, salons) may push those most at risk of CMM-inducing behaviors into exactly the higher-risk contexts we are trying to control and may therefore have the unintended consequence of actually increasing the potential for harm

16 Speaking as a citizen of North Carolina 16 Thank you for your time today In my work as a science policy advisor (HHS, WHO, DoD, many corporations & unions), I often find that people focus on the narrow issue at hand without consideration for the collateral and derivative consequences In this case the narrow issue at hand is the potential harm caused by indooruv exposure When I first looked at this issue, I too assumed there must be a risk I started my professional life as a research immunochemist and it seemed perfectly reasonable to assume ANY UV exposure had a significant potential for harm I regularly used UVC to induce mutagenesis in my lab As we began reviewing the research, two things struck me: (i) the research was not very good, and (ii) as I should have known, we co-evolved in a hostile, UV rich environment and developed powerfulmechanisms to deal with that environment Like everything in life, there is a delicate risk-benefit calculus inherent to our biology (it is not a perfect world), but we evolved mechanisms that work more or less (this is a complex topic) My personal concern is that policy in this area will lack nuanceand will actually adda meaningful potential for harm, especially for children (who should not be the victims of our inadequacies as doctors, researchers, or policy-makers) Simply put, there are just too many uncertainties here, especially related to how people will respond if indoor tanning salons are restricted in a way that forces consumers to change behaviors If teenagers would simply respond rationally, there would not be drug, cigarette or other risk-behavior problems in the US We can not reasonably expect peopleto recognize the risks of natural sunlight, especially when we tell them that indoor tanning salons add a special risk so much so that we ban or restrict them Of course we cannot ban sunlight or prevent burns, but that does not then mean that we should think that indoor tanning somehow posses an equivalent (and additive) risk and we should thereforeban it because we can Based on our reviews of the science, I now believe that salons will actually reduce overall risks precisely because they managethose risks (yes, they are not risk free, carcinogenesis is a numbers game), but they do prevent burns, control exposures and durations, and provide important risk awareness education to tanners These are all issues that should be considered by you as you review your options I fully understand that we all share the motivation of protecting the public Putting an official stamp of approval on weak science, especially when we have good reason to believe that people will think they are reducing harm by tanning outdoors, is exactly contrary to intentions of everyone interested in this issue

17 Appendix I 17 BRIEF SUMMARY OF KEY FINDINGS ABOUT THE QUALITY OF CURRENT RESEARCH LINKING INDOOR TANNING AND CUTANEOUS MALIGNANT MELANOMA

18 Brief discussion of review of the state of research regarding strength of causal linkages between tanning bed exposure and Cutaneous Malignant Melanoma (CMM) 18 The 2006 WHO/IARC report [International Journal of Cancer 120: ] is an often-cited meta analysis Based on 19 epidemiological studies Small relative risk of 115; 95% CI, Marginal statistical significance o IARC conclusions go well beyond their findings No evidence of dose-response relationship [unusual for radiological phenomena] Significant methodological flaws in analysis Failed Failsafe N analysis*: In the IARC meta analysis, removal of just one study eliminates any statistical significance [rr=101] Meta analysis had significant selection bias o This is a fragile study Only 7 studies provided any input related to age of first use (before age 35) Relative risk of 175 reported is not supported by IARC s own review experts Inadequate assessment re: influence of confounders in original studies * Failsafe N calculates the number of studies with null results that would need to be added to a meta analysis in order for the reported effect to be considered unreliable

19 Resolution of research findings & conclusions: Is their actionable information indicated in current science findings & conclusions? Several meta-analyses have suggested a modest increase of relative risk of melanoma related to ever using a tanning device (despite significant heterogeneity in the device technologies used in these studies) Uncontrolled home tanning units are included in these studies and should not be considered equivalent to controlled salon-tanning It is a methodological mistake to include multiple presumed causal UV sources into one study as if they are equivalent o There have been significant changes over the last several years in indoor tanning technology There are no non-epidemiologicalstudies that provide a robust understanding of the disease-causing disease-preventing nature of non-burning UV exposure in humans Some studies investigating tumorigenesis used long-term sustained exposure of several months (mice) as a surrogate for long-term human exposure (years) This experimental design has been criticized o o o 19 Does not take into account the normal immunological repair mechanisms and other metabolic effects that take place during gaps in exposure modalities The kind of long-duration or continuous exposure used in these types of animal studies may, in fact, promote immunosuppression that is, in and of itself, carcinogenic Animal models are not appropriate surrogates (especially non-primate studies) We prepared a more detailed analysis for the US FDA on each of the major studies This has been provided to you under separate cover