L. Lloyd Morgan Interphone Studies To Date An Examination of Poor Study Design Resulting in an UNDER-ESTIMATION of the Risk of Brain Tumors Interphone Studies To Date An Examination of Poor Study Design Resulting in an UNDER-ESTIMATION of the Risk of Brain Tumors L. Lloyd Morgan BEMS, San Diego, 12 June 2008

L. Lloyd Morgan Methodology Methodology What If There Is No Risk of Brain Tumors?  ORs 1.0  Think coin tossing OR=1.0 are excluded  ~5% of ORs would be significant  ORs 1.0  Calculate ratio: 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

L. Lloyd Morgan Methodology Methodology 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)

L. Lloyd Morgan Results Results Percent Significant Findings By Category Expectation: ~5%

L. Lloyd Morgan Results Results Ratio (OR 1.0): Exposures: >10 Year and <10 Year

L. Lloyd Morgan Results Results Ratio by Category

L. Lloyd Morgan Results Results Ratio by Brain Tumor Type

L. Lloyd Morgan Interphone 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

L. Lloyd Morgan Flaw 2 Tumors 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%)

L. Lloyd Morgan Flaw 2 Absorbed Radiation Decreases Rapidly w Depth

L. Lloyd Morgan Interphone Protocol Design Flaws  Flaw 3: Latency time  Known latency times Ionizing radiation & brain tumor: years Smoking & lung cancer: ~30 years Asbestos & mesothelioma: 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

L. Lloyd Morgan Flaws 3 and 4 Latency Time and the Definition of “Regular Users”

L. Lloyd Morgan Interphone Protocol Design Flaws  Flaw 5: Young adults and children excluded  Children and young adults at greater risk than adults Interphone Protocol: years –Some studies reduce minimum age to 20 years Underestimates risk

L. Lloyd Morgan Flaw 5 Young Adults and Children Excluded Israel: Ionizing Radiation Korea: Cellphone Rad.Sweden: Cellphone Rad.

L. Lloyd Morgan Interphone 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

L. Lloyd Morgan Interphone 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

L. Lloyd Morgan Interphone Protocol Design Flaws  Flaw 10: Recall bias  Light users underestimate use  Heavy users overestimate use  Result: Large underestimation of risk

L. Lloyd Morgan How to Resolve Flaws  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., …

L. Lloyd Morgan  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)

L. Lloyd Morgan Potential Brain Tumor Risk 30-year Latency Potential Brain Tumor Risk 30-year Latency Poisson Distribution Calculation

L. Lloyd Morgan Potential Public Health Risk

L. Lloyd Morgan Conclusions  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

L. Lloyd Morgan I Pray I’m Wrong!

L. Lloyd Morgan 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

L. Lloyd Morgan Interphone 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

L. Lloyd Morgan Design 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

L. Lloyd Morgan Design 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

L. Lloyd Morgan Design 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

L. Lloyd Morgan Tumors Outside Radiation Plume Are Unexposed Flaw 2 Tumors Outside Radiation Plume Are Unexposed

L. Lloyd Morgan Children Excluded Ionizing Radiation Example Flaw 5 Children Excluded Ionizing Radiation Example

L. Lloyd Morgan Young Adults Excluded Korean Cellphone Study Flaw 5 Young Adults Excluded Korean Cellphone Study

L. Lloyd Morgan Young Adults Excluded Swedish Cellphone Study Flaw 5 Young Adults Excluded Swedish Cellphone Study

L. Lloyd Morgan Tumors Outside Radiation Plume Are Unexposed Flaw 2 Tumors Outside Radiation Plume Are Unexposed