• 24 JAN 08
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    #847:An Independent Analysis of the Interphone Studies to Date

    From Lloyd Morgan

    Interphone Studies to Date
    An Examination of Poor Study Design
    Resulting in an Underestimates of the Risk of Brain Tumors

    Lloyd Morgan, January 23, 2008

    Introduction

    INTERPHONE is a 13-country case-control study examining the risk of
    acoustic neuroma, glioma, meningioma and parotid gland tumors from
    cellphone use. Eleven studies [1-11] have been published on the risk of
    brain tumors from cellphone use and two studies on the risk of parotid
    gland tumors (a salivary gland located near to the ear). [12-13]. Two
    of the eleven Interphones studies were studies of 5 countries [1,2],
    which partially overlap other studies. Therefore this examination
    focuses on 9 studies for risk of a brain tumor from cellphone use.

    That all 11 of the studies showed use of a cellphone provided
    “protection”¯ from a brain tumor and reported there was “no risk”¯ for
    brain tumors from “regular”¯ cellphone use, [1-11] is a fraud
    perpetrated on the public. This should not be a surprise, given that a
    substantial proportion of the cost of these studies has been paid for
    by the cellphone industry.

    As I will show, there are six major flaws in these studies, five of
    which underestimate the risk of tumors. Yet, as we will see, and this
    is very alarming, in spite of these flaws, where the tumors are on the
    same side of the head where the cellphone was held and the phone was
    used for 10 year or more, all of the results show a risk of tumors.

    Before we examine the flaws I will discuss how you can detect flaws
    similar to what exists within the Interphone Protocol. First, examine the
    full set of odds ratios (ORs) within any single study, or better yet,
    combinations of Interphone studies.

    An odds ratio (OR) is a ratio that measures the odds of cellphone
    radiation exposure for cases compared to controls. In effect, it is the
    risk of tumors from cellphone use. Cases are subjects with a disease
    (in this discussion, brain tumors). Controls are subjects without the
    disease. Controls are chosen at random, and then matched to the cases
    by various factors. Typically these factors are age, gender,
    residential region, education and social economic status (SES).
    Reported odds ratios are adjusted for each of the matched factors in
    order to minimize confounding.

    Studies report both the OR and the 95% Confidence Interval (CI). 95%
    confidence means there is >95% confidence that the result is not due to
    chance. If the CI spans 1.0 it is said to be non-significant and if it
    does not span 1.0 it is said to be significant. The reported OR is the
    most likely value within the CI.

    Let”™s suppose that there is no risk of tumors from cellphone use. What
    would you expect to find by examining all the ORs reported in a study,
    or a set of studies? If there were no risk, then regardless of the
    significance or non-significance, roughly half of the ORs would be
    elevated (OR>1.0) and roughly half would not be elevated (OR<1.0).
    Further about 95% of the ORs will be non-significant and about 5% of
    the ORs will be significant. Think about tossing a coin. About half the
    time heads comes up and about half the time tails comes up. The ratio
    of heads to tails approaches 1.0 as the number of coin tosses increase.
    Findings with OR=1.0 are not counted.

    Risk of Brain Tumors from Cellphone Use
    An examination of the ORs for all brain tumors reported by the 9
    Interphone studies found that 65 of the results had an OR>1.0 and 308
    had an OR<1.0 (observed ratio=4.7; expected ratio ~1.0).

    For significant findings, there were 3 results with OR>1.0 and 50
    results with OR<1.0 (observed ratio=16.7; expected ratio ~1.0). For
    the 3 results reporting OR>1.0, all had >10 years of exposure with the
    tumor on the same side of the head where the cellphone was held.

    It would appear that when a cellphone is used for >10 years and the
    tumor is on the same side of the head where the cellphone was used,
    there is a significant risk of a brain tumor.

    As I said in the introduction, to see if a study, or a set of studies,
    are flawed, all you have to do is to examine the odds ratios. Out of
    373 published ORs, 65 are >1.0 (20%) and 308 are <1.0 (80%). The
    ratio should be close to 1.0, but it is 4.8 (309/65=4.8). As previously
    noted, of the 271 findings we would expect, about 5% to be significant
    findings. Yet there are 53 significant findings (14%) when the expected
    would be about 14 (5%).

    A closer examination of all the significant findings for <10 is
    incredulous. There are 50 significant findings with OR<1.0 and zero
    significant findings with OR>1.0. A significant OR<1.0 indicates
    that cellphone use protects the user from brain tumors! There are two
    possible conclusions to explain this incredulity: either using a
    cellphone provides protection from brain tumors, or there are major
    flaws in the studies.

    Now let”™s examine the 6 design flaws in the Interphone studies. Five of
    these flaws result in an underestimation of risk. Could this be the
    reason that there are 50 significant finding showing a protection and
    none showing a risk of brain tumors from cellphone use?

    Flaw 1: Selection Bias
    The first flaw is called selection bias. It is likely the result of the
    low percentage of controls that participated in the studies (weighted
    average of 59%). Think about being randomly selected for a cellphone
    study. You are told you will be asked to answer a long questionnaire.
    If you use a cellphone you are more likely to agree to participate than
    if you do not use a cellphone. If this happens it is called selection
    bias. Selection bias will result in an underestimation of risk.

    Flaw 2: Inclusion of Tumors Outside the Cellphone”™s Radiation Plume
    The second flaw is the inclusion of all brain tumors without regard to
    their location. Because the cellphone”™s radiation plume only penetrates
    a short distance into the head, nearly all of this radiation is
    absorbed by the temporal lobe, the acoustic nerve, or the parotid gland
    (not discussed in this column).

    Even when cellphone exposure of one side of the head is considered on
    the side where the cellphone was held, a substantial portion of half
    the brain is unexposed (the opposite side is completely unexposed).

    The colors in Figure 2 indicate The Specific Absorption Rate (SAR) of
    is the amount of power absorbed by brain tissue, in
    this discussion, brain tissue, in Watts per kilogram.

    The temporal lobe and the acoustic nerve, the nerve from the ear to the brain (not shown), and the parotid gland, absorb almost all of the cellphone”™s radiation plume. The plume is only a small portion of the brain and is entirely on the side of the head where the cellphone is used. The depth of the cellphone”™s radiation plume”™s
    penetration is quite shallow. More that 67% of the radiation plume”™s
    power is absorbed within an inch (2.54 cm) of the surface of the skull.

    Studies that include brain tumors outside of the cellphone radiation
    plume underestimate the risk of brain tumors.

    Flaw 3: Latency Time and Definition of Regular User
    The third flaw is the definition of “regular”¯ cellphone use in relation
    to a reasonable latency time. “Regular”¯ cellphone use is defined as use
    of a cellphone on average once per week for at least 6 months. Exposure
    within 1 year of the diagnosis date is not considered. The result of
    this definition, combined with the incredibly fast rate of new
    cellphone users, is to overweight “regular”¯ users with, an incredibly
    large group of short-term users, far too short a time to expect a tumor
    to be diagnosed.

    Latency time is the time from an exposure to the diagnosis of a tumor.
    What we know about the latency time for brain tumors comes from
    ionizing radiation exposures. Based on ionizing radiation, the latency
    time for brain tumors is between 25 and 40 years, similar to the
    latency time of lung cancer from tobacco exposure.

    For the 9 Interphone studies, using weighted averages for cases or
    controls, we see that 0.61% of cases and 10% of controls have used a
    cellphone for 10 years or more, and 18% of cases and 21% of controls
    have used a cellphone for 5 years or more.

    The result: for a reasonable latency time, it would be unlikely to find
    any risk of tumors, given the percentage of cases and controls. Yet, as
    we saw in the Studies on the Risk of Brain Tumors from Cellphone Use
    section, there is a risk. “It would appear that when a cellphone is
    used for >10 years and the tumor is on the same side of the head where
    the cellphone is used, there is a significant risk of a brain tumor.”¯

    Because such a large percentage of “regular”¯ users have used a
    cellphone for an unreasonably short latency time the reported results
    for <10 years as well as for >10 years (6.3% of cases) are an
    underestimation of risk.

    Flaw 4: Children and Young Adults Are Not Included in Interphone Studies
    The Interphone Protocol states that cases be between 30 and 59 years of
    age. While a few studies have included cases as young as 20, the
    non-inclusion of <20 year olds results in an underestimation of
    risk. Why? Because children, with their high rate of cell division, are
    at higher risk of tumors than adults. As we know there a considerable
    proportion of cellphone use by children. And, we know that children,
    especially teenagers, spend more time on cellphones that do adults.

    Flaw 5: Cellphone”™s Radiated Power
    It is reasonable to expect that risk of a tumor from a cellphone, after
    a reasonable latency time, would be the cellphone”™s power multiplied by
    cumulative time of use. In the early days of cellphone use all
    cellphones used analog technology. These always radiated a fixed amount
    of power (~2 Watts). Analog cellphones use has been totally displaced
    by digital cellphones. Digital cellphones have a feature called
    Automatic Power Control or APC. At the beginning of a call the
    cellphone radiates maximum power (~2 Watts) but quickly reduces the
    power so the radiated power is sufficient to have a reliable link to
    the cell tower (AKA masks or base stations). The result is that
    cellphones radiate far less power in urban areas compared to rural
    areas. This is because cell phone towers are much closer in urban areas
    compared to rural areas so the cellphone radiates less power in urban
    areas and more power in rural areas. When rural and urban cellphones
    are not reported separately the result is an underestimation of risk.

    Flaw 6: Number of Cases Included in a Study
    The weighted average time in these 9 studies for a case to be eligible
    for inclusion in the study was only 2.6 years. When one considers 4 of
    the 5 previous flaws, it becomes obvious that such a short period of
    time for eligibility will result in too few cases to resolve these
    flaws. For example, if tumors were limited only to the exposed region
    of the brain then there would be far fewer cases; if a reasonably long
    latency time was included, again there would be far fewer cases; if
    children had been included there would have been more cases; and, if
    rural users were to be compared to the far larger number of urban users
    a much larger number of cases would need to be eligible to participate
    in the Interphone Study.

    Conclusion and Discussion
    With five flaws, each independently underestimating the risk of tumors,
    it is no wonder why the Interphone studies report a large number of
    results suggesting cellphone use protects the user from having a brain
    tumor.

    The Interphone Study has substantial funding from the cellphone
    industry. The additional cost to resolve these flaws could have been
    accomplished if the industry provided more funds. In addition if the
    participating countries had anticipated the potential cost of a
    pandemic of brain tumors, the cost effectiveness of contributing
    substantially more funds, would have been obvious. Lastly, relying on
    the cellphone industry funding is equivalent to having the fox guard
    the hen house.

    The cellphone industry will state that there is a “firewall”¯ between
    their funds and the research teams who do the studies. While it is true
    that the cellphone industry provides the funds to another organization
    (UICC) which then decides on the teams that will do each study, the
    researchers are aware that most of their funds are coming from the
    cellphone industry. While I do not doubt the integrity of the
    researchers, I also believe there in an inherent conflict-of-interest,
    best described by the saying, “Don”™t bite the and that feeds you.”¯

    The fundamental problem is not conflict-of-interest. The fundamental
    problem is the Interphone Protocol. While I have no evidence, it would
    appear that the cellphone industry influenced the Protocol, if not
    actively participating in its creation. The end result is the Protocol
    is designed to not find any risk. That it has found a risk is sobering!

    Tragically, the window of time to do a large, well-designed
    case-control study is closed. Case-control studies require exposed and
    unexposed subjects. It is no longer possible to find unexposed
    subjects.

    References
    1. Schoemaker et al. Mobile phone use and risk of acoustic neuroma:
    results of the Interphone case””control study in five North European
    countries. British Journal of Cancer. 2005 Oct 3; 93 (7): 842-8. A
    Scandinavian and United Kingdom Interphone Study reporting, “The risk
    of acoustic neuroma in relation to regular mobile phone use in the
    pooled data set was not raised . . .”¯
    2. Lahkola et al. Mobile phone use and risk of glioma in 5 North
    European countries. International Journal of Cancer: 120, 000″”000
    (2006). A Scandinavian and UK Interphone Study reporting, “We found no
    evidence of increased risk of glioma related to regular mobile phone
    use . . .”¯
    3. Lonn et al. Mobile Phone Use and the Risk of Acoustic Neuroma.
    American Journal of Epidemiology 2004; 159:277″”283. A Swedish
    Interphone Study reports, “The overall odds ratio for acoustic neuroma
    associated with regular mobile phone use was 1.0.”¯ [i.e., no risk]
    4. Christensen et al. 2004, Cellular Telephone Use and Risk of Acoustic
    Neuroma. American Journal of Epidemiology, Vol. 159, No. 3, 2004;159:
    277″”283. A Danish Interphone Study reporting, “We did not observe
    increased risk of acoustic neuroma among regular cell phone users . .
    .”¯
    5. Lonn et al. Long-Term Mobile Phone Use and Brain Tumor Risk,
    American Journal of Epidemiology 2005; 161: 526″”535. A Swedish
    Interphone Study reporting, “For regular mobile phone use [there was no
    risk) for glioma . . .and for meningioma.”¯
    6. Christensen et al. Cellular telephones and risk for brain tumors: A
    population-based, incident case-control study. Neurology. 2005 Apr 12
    ;64 (7): 1189-95. Erratum in: Neurology. 2005 Oct 25; 65 (8):1324. A
    Danish Interphone Study of glioma and meningioma reported, “The overall
    analyses did not reveal an increased risk for . . . regular use of a
    cellular telephone . . .”¯
    7. SchĆ¼z et al. Cellular Phones, Cordless Phones, and the Risks of
    Glioma and Meningioma (Interphone Study Group, Germany). American
    Journal of Epidemiology 2006 Mar 15; 163 (6): 512-20. Epub 2006 Jan 27.
    A German Interphone Study reporting, “For regular cellular phone use
    [there was no risk] . . . for glioma and . . . for meningioma.”¯
    8. Takebashi et al. Mobile phone use and acoustic neuroma risk in
    Japan. Occupational Environmental Medicine, 2006; 63; 802-807. A
    Japanese Interphone Study reporting, “No significant increase of
    acoustic neuroma risk was observed . . . when regular mobile phone . .
    . was [used].”¯
    9. Klaeboe et al. Use of mobile phones in Norway and risk of
    intracranial tumours. European Journal of Cancer Prevention 2007,
    16:158″”164. A Norwegian Interphone Study reporting, “No increased risk
    was observed for gliomas, meningiomas . . . and acoustic neuromas . . .
    among regular mobile phone users . . .”¯
    10. Hours et al. Cell Phones and Risk of brain and acoustic nerve
    tumours: the French INTERPHONE case-control study. Revue
    d”™Ć‰pidĆ©miologie et de SantĆ© Publique 2007 Oct, 55 (5): 321-32. Epub
    2007 Sep 11. French. A French Interphone Study reporting, “Regular cell
    phone use was not associated with an increased risk of neuroma . . .”¯
    11. Hepworth et al. Mobile phone use and risk of glioma in adults:
    case-control study. BMJ Online First bmj.com. A United Kingdom
    Interphone Study reporting, “Overall, we found no raised risk of glioma
    associated with regular mobile phone use . . .”¯
    12. Sadetzki et al. Cellular Phone Use and Risk of Benign and Malignant
    Parotid Gland Tumors””A Nationwide Case-Control Study. American Journal
    of Epidemiology Advance Access published December 6, 2007. An Israeli
    Interphone Study.
    13. Lƶnn et al. Mobile phone use and risk of parotid gland tumor.
    American Journal of Epidemiology 2006 Oct 1; 164 (7): 637-43. Epub 2006
    Jul 3. A Swedish Interphone Study.

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