Teachers' Cancers La Quinta Middle School 1988-2005 Sam Milham, MD ...

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  • Teachers' Cancers La Quinta Middle School 1988-2005 Sam Milham, MD ...

    1. 1. L. Lloyd Morgan [bilovsky@aol.com] 1 Interphone Studies To DateInterphone Studies To Date An Examination of Poor Study DesignAn Examination of Poor Study Design Resulting in an UNDER-ESTIMATIONResulting in an UNDER-ESTIMATION of the Risk of Brain Tumorsof the Risk of Brain Tumors L. Lloyd Morgan BEMS, San Diego, 12 June 2008
    2. 2. L. Lloyd Morgan [bilovsky@aol.com] 2 MethodologyMethodology What If There Is No Risk of Brain Tumors?  ORs <1.0 would be ~equal ORs>1.0  Think coin tossing • OR=1.0 are excluded  ~5% of ORs would be significant  ORs <1.0 would be ~equal ORs>1.0  Calculate ratio: OR<1.0/OR>1.0  13 Interphone brain tumor studies to date • Exclude 2 overlapping studies and recent (Schlehofer) study • Analysis restricted to 10 Interphone brain tumor studies  Calculate binomial p-values
    3. 3. L. Lloyd Morgan [bilovsky@aol.com] 3 MethodologyMethodology Calculate Ratio by Categories by Studies  How to have statistically independent categories?  Compare between studies, not within studies  Categories • Brain Tumors – All – Acoustic Neuroma – Glioma – Meningioma • Years of use (Years) • Cumulative hours of use (Hours) • Cumulative number of calls (Call #) • “Regular” cellphone use (“Regular”) • Years of ipsilateral cellphone use (Years Ipsi) • Years of contralateral cellphone use (Yrs Contra) • Minutes of cellphone use per day (Min/Day)
    4. 4. L. Lloyd Morgan [bilovsky@aol.com] 4 ResultsResults Percent Significant Findings By Category Expectation: ~5% 0% 5% 10% 15% 20% 25% All Years Hours Call # "Regular" Years Ipsi Years Contra Min per Day Categories ~ expected Based on 7 Findings 0%
    5. 5. L. Lloyd Morgan [bilovsky@aol.com] 5 ResultsResults Ratio (OR<1.0/OR>1.0): Exposures: >10 Year and <10 Year 0.0 1.0 2.0 3.0 4.0 5.0 >10 year <10 year Ratio Longest Exposure Lowest Ratio p=0.16 p=3.6 x 10 -22 ~ Expected ratio if no risk
    6. 6. L. Lloyd Morgan [bilovsky@aol.com] 6 ResultsResults Ratio by Category 0 1 2 3 4 5 6 7 8 All Call # Hours Years "Regular" Years Contra Min per Day Years Ipsi Categories Ratio p=1.2x10-20 p=6.0x10-07 p=6.1x10-06 p=1.1x10-07 p=0.0011 p=0.0097 p=0.16 p=0.097 Highest Exposure Lowest Ratio Non-significant Near-significant
    7. 7. L. Lloyd Morgan [bilovsky@aol.com] 7 ResultsResults Ratio by Brain Tumor Type 0 1 2 3 4 5 6 All Acoustic Neuroma Glioma Meningioma Ratio p=1.2x10-20 p=2.9x10-5 p=6.0x10-10 p=8.2x10-9
    8. 8. L. Lloyd Morgan [bilovsky@aol.com] 8 Interphone Protocol Design FlawsInterphone Protocol Design Flaws  Flaw 1: Selection Bias  Participating controls use cellphones more than non- participating controls • Weighted average control participation rate: 59% • Löon 2004: 20% control refused; 34% used, 59% did not use  Underestimates risk  Flaw 2: Tumors outside the radiation plume are unexposed  Unexposed tumors treated as exposed  Plume volume small relative to brain volume • Well know since 1994 (4 previous papers)  Underestimates risk
    9. 9. L. Lloyd Morgan [bilovsky@aol.com] 9 Flaw 2Flaw 2 Tumors Outside Radiation Plume Are UnexposedTumors Outside Radiation Plume Are Unexposed  Radiation plume’s volume is small % of brain’s volume  Ipsilateral: exposed Contralateral: unexposed  Absorbed radiation decreases rapidly with plume penetration depth • Half-way to the brain’s mid-line, >90% of energy is absorbed  Percentage of absorbed cellphone radiation  Ipsilateral temporal lobe: 50-60% (wt. av.=53%) • ~15% of brain’s volume  “Ipsilateral” cerebellum: 12-25% (wt. av.=19%) • ~5% of brain’s volume  62-85% of absorbed radiation is in ~20% of the brain’s volume  Plume decreases rapid with depth (actual exposed brain’s volume: <20%, perhaps 15%)
    10. 10. L. Lloyd Morgan [bilovsky@aol.com] 10 Flaw 2Flaw 2 Absorbed Radiation Decreases Rapidly w DepthAbsorbed Radiation Decreases Rapidly w Depth Relative Absorbed Radation and Penetration Depth in Temporal Lobe 0% 10% 20% 30% 40% 50% 60% 15-24 25-34 35-44 45-54 55-64 65-74 75-84 Depth (mm) % Absorbed Radiation Relative to Max Absorbed Radiation 900 MHz European Phones (worst case) 800-900 MHz Japanese Phones Source: Cardis et al 2008
    11. 11. L. Lloyd Morgan [bilovsky@aol.com] 11 Interphone Protocol Design FlawsInterphone Protocol Design Flaws  Flaw 3: Latency time  Known latency times • Ionizing radiation & brain tumor: 20-40 years • Smoking & lung cancer: ~30 years • Asbestos & mesothelioma: 20-40+ years  Short latency times underestimates risk  Flaw 4: Definition of “regular” user  “Regular” user: At least once a week for 6 months or more • If definition of “regular” smoker were used, would a risk of lung cancer be found?  Definition of “regular” user underestimates risk
    12. 12. L. Lloyd Morgan [bilovsky@aol.com] 12 Flaws 3 and 4Flaws 3 and 4 Latency Time and the Definition of “Regular Users”Latency Time and the Definition of “Regular Users” UK Subscribers by Year 0 10 20 30 40 50 60 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Years from Eligibility Date (Latency Time) Millions 0 Wt. Ave. Eligibility Date 2002.5 123456789101112131415 <5 year latency 85% User-Year >5 year latency 15% User-years >10 year latency 2% User-years
    13. 13. L. Lloyd Morgan [bilovsky@aol.com] 13 Interphone Protocol Design FlawsInterphone Protocol Design Flaws  Flaw 5: Young adults and children excluded  Children and young adults at greater risk than adults • Interphone Protocol: 30-59 years – Some studies reduce minimum age to 20 years • Underestimates risk
    14. 14. L. Lloyd Morgan [bilovsky@aol.com] 14 Flaw 5Flaw 5 Young AdultsYoung Adults andand ChildrenChildren ExcludedExcluded 0 1 2 3 4 20-29 years 30-39 years 40-49 years 50-59 years Age Range OR P<0.01 Source: J.W. Choi el al.Case-control Studies on Human Effects of Wireless Phone RF in Korea, BEMS 2006 Increased Risk of Brain Tumor 0 1 2 3 4 5 6 7 8 20-80 years 20-29 years 20-80 years 20-29 years Analog cellphone Cordless phone OR Source: Hardell et al. Arch Environ Health. 2004 Mar;59(3):132-7. Israel: Ionizing Radiation Korea: Cellphone Rad. Sweden: Cellphone Rad. Excess Relative Risk (ERR) per Gray (Gy) Malignant Brain Tumors by Age from Ionizing Radiation Exposure 356% 224% 47% 0% 100% 200% 300% 400% <5 5-9 10+ Age at Exposure ERR/GY Mean estimated dose: 1.5 Gy (range 1.0 to 6.0 Gy) Source: Sadetzki et al., RADIATION RESEARCH 163, 424–432 (2005)
    15. 15. L. Lloyd Morgan [bilovsky@aol.com] 15 Interphone Protocol Design FlawsInterphone Protocol Design Flaws  Flaw 6: Comparison cellphone radiated power: higher vs lower  Analog Vs Digital phones • No longer possible  Rural Vs Urban users  Underestimates risk
    16. 16. L. Lloyd Morgan [bilovsky@aol.com] 16 Interphone Protocol Design FlawsInterphone Protocol Design Flaws  Flaw 7: Cordless phone, walkie-talkie, Ham, and proximity to TV & radio transmitters  Treated as unexposed  Underestimation of risk  Flaw 8: Exclusion of brain tumor types  Includes only acoustic neuroma, glioma & meningioma  Other brain tumor types are excluded • For example lymphoma and neuroepithelial brain tumors  Underestimates risk  Flaw 9: Exclusion of brain tumor cases because of death  Underestimates risk of most deadly brain tumors
    17. 17. L. Lloyd Morgan [bilovsky@aol.com] 17 Interphone Protocol DesignInterphone Protocol Design FlawsFlaws  Flaw 10: Recall bias  Light users underestimate use  Heavy users overestimate use  Result: Large underestimation of risk
    18. 18. L. Lloyd Morgan [bilovsky@aol.com] 18 How to ResolveHow to Resolve FlawsFlaws  Increase diagnosis eligibility time  Nine Interphone studies: weighted-average 2.6 years • Hardell et al. eligibility time: 6 years  Lower age range to <15 years  Pay controls (and cases?) for participation in study  Do not tell controls what is the purpose of the study  Interview proxies in case of death  Separately report both case and proxy interview results  Treat unexposed tumors as unexposed  Etc., Etc., Etc., …
    19. 19. L. Lloyd Morgan [bilovsky@aol.com] 19 Conflict-of-InterestConflict-of-Interest  Cellphone Industry  Interphone funding is inadequate to resolve flaws • More funding, greater potential of substantial revenue loss  Researchers’ conflict-of-interest (unconscious?)  Source of funds is known in spite of “Firewall”  Honest, but  “Don’t bite the hand that feeds you” • 90 significant protective results – Ignored by authors (no commentary in the text)
    20. 20. L. Lloyd Morgan [bilovsky@aol.com] 20 Potential Brain Tumor RiskPotential Brain Tumor Risk 30-year Latency30-year Latency Poisson Distribution Calculation 0% 20% 40% 60% 80% 100% 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 Years Since First Exposure Risk 1985 1st Use 1995 10 Yrs 2005 20 Yrs 2015 30 Yrs 0.002% 4% 55% 97%
    21. 21. L. Lloyd Morgan [bilovsky@aol.com] 21 Potential Public Health RiskPotential Public Health Risk Potential Brain Tumor Cases From Use of a Cellphone Assuming a 30-Year Latency Time and 10% of Users 1 Diagnosed with a Brain Tumor 0 200,000 400,000 600,000 800,000 1,000,000 1,200,000 1,400,000 1,600,000 1,800,000 19851986 198719881989 19901991199219931994 1995199619971998199920002001 200220032004 20052006 200720082009 20102011 201220132014 20152016201720182019 Potential Cases of Brain Tumors per Year 0 50 100 150 200 250 300 350 400 450 Cellphone Subscribers millions Year 2004 44,447 Dx ~3,600 from cellphone use Year 2019 1,590,513 1 Based on 10% of long-term smokers are diagnosed with lung cancer Source Cellphone Subscribers: CTIA Source brain tumor diagnosed in 2004: CBTRUS
    22. 22. L. Lloyd Morgan [bilovsky@aol.com] 22 ConclusionsConclusions  Interphone results substantially underestimate the risk of brain tumors  Great majority of results have OR<1.0 • Either cellphone use is protective, or the study has major flaws  Ratio is lowest for highest exposures: ipsilateral use or >10 years of use  Significant risk found for >10 years and ipsilateral use  Without design flaws Odds Ratios would increase substantially  Cellphone industry’s conflict-of-interest is obvious  Government: ignores potential epidemic (see no evil)  Public health impact is enormous  Industry independent studies are required
    23. 23. L. Lloyd Morgan [bilovsky@aol.com] 23 I Pray I’m Wrong!
    24. 24. L. Lloyd Morgan [bilovsky@aol.com] 24 Now What?Now What? Based on CBTRUS Incidence Data  Window closed for case-control studies  No unexposed cases remain  Cohort studies  Unable to know users of company owed cellphones  Unable to interview cellphone users  Requires enormous numbers • 1,000,000 user-years will find (assuming cellphones do not increase risk) – ~6 acoustic neuromas – ~54 gliomas – ~45 meningiomas  Requires ~1 billion user-years to analyze by • Gender, SES, Years of use ,Exposed tumors only  Requires 30 year cohort study
    25. 25. L. Lloyd Morgan [bilovsky@aol.com] 25 Interphone Protocol Design FlawsInterphone Protocol Design Flaws  Flaw 11: Recall bias  Interview cases immediately after diagnosis and 6 months after surgery • Improved memory and cognition 6 months after surgery  Flaw 12: Observational bias  Interviewer not blinded with face-to-face interviews • Mailed questionnaires provide blindness – Supplement by phone as necessary  Flaw 13: Too few cases for statistical power  Nine Interphone Brain Tumor Studies: Use for >10 years • Average 18 cases per study • At minimum requires 2-fold more cases and controls for sufficient statistical power
    26. 26. L. Lloyd Morgan [bilovsky@aol.com] 26 Design Changes to Resolve FlawsDesign Changes to Resolve Flaws  Treat unexposed tumors as unexposed  Tumors outside radiation plume • Data was available, but to date not used, or even discussed – Too few cases?  Treat RF/MW exposures and exposed  Cordless phone, walkie-talkie radios, Ham transmitters  Overweight rural users or increase eligibility time  Compare risk of brain tumor with rural and urban users • Requires sufficient number of cases and controls  Use questionnaires not face-to-face interviews
    27. 27. L. Lloyd Morgan [bilovsky@aol.com] 27 Design Changes to Resolve FlawsDesign Changes to Resolve Flaws  Reporting “regular” use  Do not publish “regular” use data  At minimum report “regular” use for >5 years, or >10 years • Assumes >3-fold increase in case eligibility range  Latency time: initiation or promotion?  Some researchers assume cellphone can only be promoters • What is evidence for initiation vs promotion?  Follow cases & controls for a longer period
    28. 28. L. Lloyd Morgan [bilovsky@aol.com] 28 Design Changes to Resolve FlawsDesign Changes to Resolve Flaws  Increase eligibility time to 9 years (for sufficient statistical power) • >3-fold increase in cases and controls • Publish results every 3 years • Provides longer latency time • Resolves whether cellphones use initiates or promotes tumors
    29. 29. L. Lloyd Morgan [bilovsky@aol.com] 29 Flaw 2 Tumors Outside Radiation Plume Are UnexposedTumors Outside Radiation Plume Are Unexposed 900 MHz European Phone: Depth by Structure 0% 10% 20% 30% 40% 50% 60% 15-24 25-34 35-44 45-54 55-64 65-74 75-84 Depth (mm) Relative SAR Temporal Frontal Parietal Occipital Cerebellum 50% 19% Total Raditaion Absobed by Structure 9% 5% 12%
    30. 30. L. Lloyd Morgan [bilovsky@aol.com] 30 Flaw 5 Children ExcludedChildren Excluded Ionizing Radiation ExampleIonizing Radiation Example Excess Relative Risk (ERR) per Gray (Gy) Malignant Brain Tumors by Age from Ionizing Radiation Exposure 47% 224% 356% 0% 100% 200% 300% 400% <5 5-9 10+ Age at Exposure ERR/GY Mean estimated dose: 1.5 Gy (range 1.0 to 6.0 Gy) Source: Sadetzki et al., RADIATION RESEARCH 163, 424–432 (2005)
    31. 31. L. Lloyd Morgan [bilovsky@aol.com] 31 Flaw 5 Young Adults ExcludedYoung Adults Excluded Korean Cellphone StudyKorean Cellphone Study 0 1 2 3 4 20-29 years 30-39 years 40-49 years 50-59 years Age Range OR P<0.01 Source: J.W. Choi el al.Case-control Studies on Human Effects of Wireless Phone RF in Korea, BEMS 2006
    32. 32. L. Lloyd Morgan [bilovsky@aol.com] 32 Flaw 5 Young Adults ExcludedYoung Adults Excluded Swedish Cellphone StudySwedish Cellphone Study Increased Risk of Brain Tumor 0 1 2 3 4 5 6 7 8 20-80 years 20-29 years 20-80 years 20-29 years Analog cellphone Cordless phone OR Source: Hardell et al. Arch Environ Health. 2004 Mar;59(3):132-7.
    33. 33. L. Lloyd Morgan [bilovsky@aol.com] 33 Flaw 2 Tumors Outside Radiation Plume Are UnexposedTumors Outside Radiation Plume Are Unexposed Source: http://serendip.brynmawr.edu/bb/kinser/Glossary.html ~10.4 cm ~5.6 cm Surface area ~162 cm2 Ipsilateral temporal lobe’s volume to total brain’s volume ~15% Worst case: ~62% of ipsilateral radiation is absorbed in ~20% of brain Ipsilateral cerebellum’s volume to total volume ~5%

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