Thursday, October 3, 2013

Million Women Study: Shoddy Science Does Not Warrant Shoddy Conclusions

Dr. Leszczynski is one of the world's leading biologists who researches the effects of radiofrequency radiation for the Finnish government. At least he did until the Finnish government defunded his laboratory.  He was one of 31 experts invited in 2011 by the World Health Organization's (WHO) International Agency for Research on Cancer to review the cancer risks of exposure to wireless radiation. The results of this expert review was that WHO classified radiofrequency energy, especially cell phone radiation, as "possibly carcinogenic" in humans (i.e., Group 2B). Dr. Leszczynski has subsequently reported that some of the group wanted a "probably carcinogenic" or Group 2A classification.

Dr. Leszczynski has been writing an occasional column that is published on the Washington Times web site.  For his latest article, he asked six experts including two of the WHO Interphone Study investigators to comment on the United Kingdom's Million Women Study.  His interest in this study is because the study's authors interpreted the absence of evidence for increased brain cancer risk to mean that cell phone radiation does not cause cancer.

One of the experts interviewed for this column was the former director of the WHO's EMF Project. He defends the Million Women Study and argues based on the results that cell phone radiation does not cause cancer.  In contrast, the other five experts including myself criticize the study and dismiss its relevance to the cancer debate.

Despite its shortcomings, the study found significant evidence that cell phone use was associated with increased risk of acoustic neuroma, a rare, non-malignant tumor on the nerve from the ear to the brain.

The Million Women Study … shoddy design … shoddy results … shoddy conclusions

Dariusz Leszczynski, Washington Times Communities, Oct 3, 2013

HELSINKI, Finland, October 3, 2013 —The only two epidemiological cohort studies in existence examining the link between cell phone radiation exposures and brain cancer have embarrassingly poor design.

The two cohorts were established in Denmark and in UK. The original purpose was not to study cell phone radiation effects but other health problems. At some point in designing cohorts, scientists decided to ask questions about cell phone use and, as an aside, to examine brain cancer risk.

The problem is that the questions concerning cell phone use were not well thought out. It seems that epidemiologists did not care at all about details of exposure to cell phone radiation. They just wanted to know it - “roughly”.

In the first cohort, called ‘Danish Cohort’, the information on exposure of persons to cell phone radiation is completely useless for the purpose of determining whether causality exists between radiation exposure and cancer (for details see letters to the British Medical Journal and The Scientist Magazine story).

In the spring of 2013, the results from the second cohort were published  and called The Million Women Study. As seen from the description of the study, its primary goal was to examine the effects of hormone replacement therapy in women over 50 years of age.

This, by design, indicates that the results of this study apply only to a certain sex (females) and age (over 50) group and can not be freely extrapolated to the cell phone users as a whole. Furthermore, period of the exposure to cell phone radiation examined in The Million Women Study is far too short to be relevant when examining causality link between cell phone radiation and cancer.

The information about cell phone radiation exposures obtained for the study was as follows (quote from the study): “Women in the study have been asked twice about mobile phone use. In a survey conducted between 1999 and 2005 (to which about 65% of women recruited in 1996–2001 replied [sic!]), women were asked: ‘About how often do you use a mobile phone?’, and given three options to respond: ‘never’, ‘less than once a day’, ‘every day’; and ‘For how long have you used one?’ (participants were asked to provide total years of use).”

The authors did not obtain information about cell phone usage per day or week. Cell phone users talking on the phone for few minutes or for few hours per week were analyzed together. When considering the latency of brain cancer, the follow-up period was far too short to provide relevant and reliable information. This extremely limited information about the exposures to cell phone radiation is absolutely inadequate to determine whether exposures have, or have not, causal link with cancer.

The inadequacy of the collected the information on the exposure is very disturbing. It is like scientists evaluating the health risk in smokers and not asking how many cigarettes per day someone smokes.

The Million Women Study has shoddy exposure design leading to shoddy results and ending with shoddy conclusions.

The Million Women Study is, similarly with the Danish Cohort, yet another example of the complete failure of epidemiologists to design scientifically relevant study on cell phone radiation and brain cancer.

It is embarrassing to hear that some scientists consider the “epidemiological failure”, called The Million Women Study, as a “well designed” research.

Forbes’ Magazine blogger, Geoffrey Kabat of the Albert Einstein College of Medicine in New York City, in his recent post says about The Million Women Study: “The strengths of this design are two-fold.  First, it follows the actual temporal sequence, with exposure preceding disease.  Second, since information on exposure is obtained before the onset of illness, this information cannot be biased (distorted) by the presence of illness.”

Indeed, these could be the strengths of the study if the information on exposures was relevant.

Mr. Kabat writes also that: “Because of its large size and prospective design, the Million Women Study results represent an important contribution.”

Big is not always beautiful, especially when one side of the examined equation, the radiation exposure data, are shoddy.

I asked also opinions from the few prominent scientists about The Million Women Study. Here are their opinions, directly as provided via e-mails:

Michael Repacholi, retired Head of the WHO EMF Project, agrees with Geoffrey Kabat that the Million Women Study is a valuable proof of no cancer risk:

“This is a very large, well-conducted cohort study showing no increased incidence of glioma or meningioma with mobile phone use of 10 or more years. However, the study reported a trend of increasing risk of acoustic neuroma. When the results were combined with the Danish cohort study, that had a much larger number of these tumours, no statistical increase was found with mobile phone use of 10 or more years. Aside from the obvious difficulties in accurately assessing people’s exposure to mobile phones, the evidence from well-conducted epidemiological and animal studies is now establishing that mobile phone use does not cause or increase the incidence of head or neck cancers.”

The above opinion of Michael Repacholi should be also viewed in the context of his recent criticism of epidemiology. His opinion was that epidemiology is unable to provide reliable information on causality link between cell phone radiation and brain cancer. As Mr. Repacholi said in his Guest Blog on BRHP: “my concern is that there is an over-reliance on epidemiology studies.”

However, epidemiologists were cautious and did not consider the evidence provided by The Million Women Study to be as great as Kabat and Repacholi thought.

Michael Kundi of the Medical University of Vienna, Austria, considers it a very good idea to use the existing large cohorts to study cell phone radiation and cancer issue. However, he points out that the authors of the Million Women Study did not do a good job:

“It is definitely worthwhile to try and use a large cohort of people that are available for investigations like the cohort of the Million Women Study. This cohort has been used for many important health issues and will continue to be used for a variety of research questions. Having said this, I regret to say that the authors have not put much thought into the issue of mobile phone use and brain tumors. It is almost impossible to study induction of brain tumors because of the short observation period. That is, most if not all of the tumors diagnosed during the follow-up must have already existed at the time of commencing use of a mobile. This leaves us with studying effects on tumor growth rate and/or progression. In the case of glioma the peculiarities of the relationship of incidences with age have to be considered. In this cohort there are only women and they are in a narrow age range of about 60 years. The consequence of this fact is that if mobile phone use leads to an increased growth rate of the tumor and therefore an earlier diagnosis the risk estimate must be low or even less than one (because at older age the incidence is declining). The situation for acoustic neuroma is different because the age-incidence function differs from that of glioma.”

Bruce Armstrong of the Sydney University, Australia, considers that The Million Women Study is insufficient to think of down-grading the IARC classification of cell phone radiation from the current possible carcinogen category to lower one:

“A total of 1,261 primary intracranial neoplasms were diagnosed during follow-up, which is sufficient to make a potentially worthwhile contribution to literature on mobile phone use and brain tumours. Some 50,000 invasive neoplasms at other sites were also diagnosed, which can also contribute to knowledge about the relationship between other cancers and mobile phone use. Of the intracranial tumours investigated (glioma, meningioma, pituitary tumours and acoustic neuroma) only risk of acoustic neuroma was increased in women who were longer term users of a mobile phone. This result is coherent with results from the most recent case-control studies of mobile phone use and acoustic neuroma but not with the absence of increase in risk of acoustic neuroma reported from the Danish cohort study of mobile phone subscribers.  While this study adds to the evidence on the relationship between mobile phone use and intracranial tumours, it does not add sufficiently, in my opinion, to shift in either direction the IARC’s conclusion that there is limited evidence in humans for carcinogenicity of radiofrequency radiation.”

Joel Moskowitz of the University of California at Berkeley has also serious doubts about the design and quality of the outcome of The Million Women Study:

“With regard to investigating the association between cell phone use and subsequent tumor risk (which was not the primary purpose of the “million women” study), this study had several major shortcomings which would undermine its ability to find this association.  First, cell phone use was measured only at the beginning of the study, and it was assessed too crudely to expect to find an association with tumor risk. When women enrolled in the study, they were asked how many years they used a cell phone, and if they did, whether they used it daily or less than daily. The researchers had no follow up assessments to determine whether the women continued to use their cell phones over time so they had to assume that cell phone users continued to use their cell phones. More importantly, the researchers could not assess how much time the women spent on a cell phone either before or during the course of the study so women who used a few minutes almost every day at baseline would be lumped together with women who used their phone a half hour or more per day.  Second, the study failed to assess cordless phone use which likely exceeded cell phone use among these women due to the high cost of cell phone minutes during this period.  Cordless phone use has been found in other research to increase brain tumor risk. Third, brain tumors can take several decades to develop and few women in this study had used their cell phones for ten or more years.  Fourth, about 40% of the 1.3 million women who participated in the study were excluded from the cell phone analyses—most because they failed to provide any cell phone information. This large loss of research participants limits how generalizable the study findings are and could have biased the results. Despite these major shortcomings, the study reported a statistically significant doubling of risk of acoustic neuroma, a tumor on the nerve from the ear to the brain, among those who used cell phones for 10 or more years. Moreover, this association was related to the number of years of cell phone use.”

Mark Elwood, of the University of Auckland in New Zealand is not convinced that the provided evidence is sufficiently reliable to convince the scientists and the general public alike:

“These scientists took the opportunity of asking a few questions about cell phone use in the huge British ‘Million Women’ study, where women attending breast cancer screening clinics were invited. Over the next 10 or more years, women (average age 59) who reported the most use of cellphones had the same risk of developing brain cancers than women who did not use cellphones  at the time that was asked (and also, the same risk of all cancers, and of 18 major types of cancer). So, another of many studies showing no risk from using cellphones, but like all other studies, it can’t prove that there’s no risk. In the many analyses, there was an increased risk of one rather rare tumor, based on only 8 cases; but that was acoustic neuroma, a tumor of the nerve to the ear, and therefore in the high exposure zone from cellphones. And the study doesn’t cover men, younger people, or risks beyond about 10 years. So the debate will continue.”

Elisabeth Cardis, of CREAL-Centre for Research in Environmental Epidemiology in Spain and formerly Principal Investigator of the Interphone Project, is cautious and considers results of The Million Women Study as too weak:

“Am a bit surprised at the lack of mention of the acoustic neuroma results in the conclusion - particularly since this and glioma are the two tumour types for which their is currently the most evidence from other studies (including Interphone and the Japanese study). It seems that the first questionnaire about mobile phone use was asked over a long time period 1999-2005 but the follow-up is correctly calculated from the time the questionnaire was asked. Of the 1261 intracranial CNS tumours, 754 occurred among those who reported ever use at first questionnaire.

Only 90 of these, however, were among women who reported using the phone every day and 100 among those who reported 10+ years of use. Numbers get even smaller when the first 3 years of follow-up are excluded - 91 with 10+ years. It would be nice to see results by some form of amount of use, but obviously the information collected is very limited - ever use, daily use and number of years - but perhaps looking at categories of daily use in different periods of time since start … but the numbers would get very small.”

From the above comments of prominent epidemiologists the general conclusion can be drawn that despite the size of The Million Women cohort, the numbers of tumors are small and the information about the cell phone use is nonexistent. Therefore, it is not possible to draw any scientifically reliable conclusions based on the results of The Million Women Study.

Setting up large cohort for epidemiological study is expensive and laborious. That is why it is indeed a very good idea to use the already existing cohorts to examine causality link between cell phone radiation exposures and brain cancer.

However, the radiation exposure information, both the length and the strength/intensity of exposure, must be properly collected. Scientists working on the Danish Cohort and The Million Women Study, failed in the study design. Radiation exposure information collected in both cohorts is shoddy.

It is very disappointing that yet again epidemiologists failed. They used funds to provide us with shoddy studies. What is very worrying is the fact that these studies were published in peer-review journals and are now considered, by some, as “reliable scientific evidence”.

It is simply an embarrassing show of scientific incompetence.