Kundi phones compared with mobile phones, it is not a rational procedure to exclude them from total exposure (for information on ado- lescent users, see Söderqvist et al. 2008). The fraction of cordless phone users among cases and controls not using mobile phones ranged from about 22% in the study of Hardell et al. (2006b) to almost 40% in the German Interphone study (Schüz et al. 2006a). If we arbitrarily assign sensitivity of exposure deter- mination from omission of cordless phone use a value of 74% in cases and 78% in con- trols, assuming 100% specificity (in cases and controls) and an actual exposure prevalence of 54% [according to the data of Hardell et al. (2006b)], a true OR of 1.5 would be reduced to 1.2. Still greater reductions of the OR result if the differences in cordless phone use were actually greater. In the Interphone studies, data acquisi- tion concerning exposure was predominantly done by computer-assisted personal interview (CAPI). In about 95% of glioma cases and controls, exposure assessment was based on CAPI (Cardis et al. 2007). Reports from five Nordic countries (Lahkola et al. 2007) reveal that > 40% of cases were interviewed in the hospital. However, this fraction ranges from almost 100% in Finland to 3% in the United Kingdom. Data acquisition was completely dif- ferent in the studies of Hardell and colleagues (Hardell et al. 2002a). They sent a question- naire to home addresses of cases and controls, and upon return, they evaluated the question- naires for errors, omissions, and discrepancies. If necessary, additional information was sought by telephone interviews blinded to case status. Method of data acquisition could be important in several respects: a) interviews not blinded to case status may introduce a bias from the expectations of the interviewer; b) the interaction between interviewee and interviewer as such can lead to bias (Rosenthal effects); c) answering a questionnaire at home is less demanding (especially considering the conditions after surgery) than personal interviews; d) at home it is possible to check telephone bills or to inspect contracts with network providers to verify data. For these reasons, the questionnaire method seems to be superior to the interview technique. However, there are also advantages of the CAPI method: data can be immediately checked for errors and discrepancies, and the interviewer can explain points that are not clear and may help in recalling inquired items. Validation stud- ies (Berg et al. 2005; Vrijheid et al. 2006a, 2006b) within the Interphone study showed only a moderate correlation between self- reported intensity of mobile phone use and traffic data from network operators, but con- firmed usage data as valid proxy for micro- wave exposure. For the (not very important) recent mobile phone use, self reports seem to 320 be fairly accurate, but for earlier use, no data on reliability are available. Considering results from Christensen et al. (2005), memory per- formance is decreased especially in patients with high-grade glioma. Exposure assessment in these patients could be particularly biased if conducted by interviews compared with the questionnaire method. Bias often represents underreporting of mobile phone use, because it is more likely that a patient forgot using a mobile phone once years ago compared with falsely stating mobile phone use. In the Interphone studies, overall partici- pation was 65% for glioma cases, 78% for meningioma, and 82% for acoustic neuroma (Cardis et al. 2007). For controls, participa- tion was 53% but there was large variation across centers, ranging from 35% to 74%. Hardell et al. (2006d), using postal question- naires, reported participation rates of 88–91% in cases and 84–92% in controls. The par- ticipation rate in cases was computed based on eligible cases that received a questionnaire, defined as those with ascertained primary brain tumors alive at the time of identifica- tion and whose participation was not denied by their physician. If the definition of eligible cases for the Interphone studies were applied, the participation rate would amount to about 65–85% in the different studies of Hardell and colleagues. In the Interphone studies, on average, 13% (range, 2–44%) of case inter- views were performed as proxy interviews. As shown by Vrijheid et al. (2006a) in an Interphone validation study, response bias due to differential selection of groups of the popu- lation with higher prevalence of mobile phone use possibly has the highest impact, even outweighing recall bias. Lönn et al. (2005) showed that nonparticipating cases had almost the same proportion of mobile phone users (50% compared with 52% in participants), but nonparticipating controls differed mark- edly from participants (34% compared with 59%). Effect of this selection bias might be even greater if long-term use is considered. Consequence of selection bias can easily be determined because the biased OR is equal to the product of the true OR and the selec- tion OR (cf. Rothman et al. 2008). Given the nonresponse analysis of Lönn et al. (2005), the selection OR is computed as 0.64 if over- all participation rates of the Interphone stud- ies are considered (72% and 53% in cases and controls, respectively). All 46 ORs in the report of Lönn et al. (2005), except one in the overall analysis of glioma and meningioma, were < 1. Assuming the selection OR is 0.75 as computed based on the participation rates for the Lönn study specifically (79% in cases and 70.5% in controls), almost all these ORs would increase above 1 and none would be significantly < 1 (as was the case for 7 of the 46 ORs). For example, the OR for > 10 years of mobile phone use for glioma, reported as 0.9, would increase to 1.2. As has been pointed out previously (Kundi 2004; Kundi et al. 2004; Schoemaker et al. 2005), early symptoms of a developing brain tumor may have influenced behavior regarding mobile phone use. In particular, growing acous- tic neuroma are frequently associated with hear- ing problems and tinnitus. Such symptoms may lead to a restriction of use, change of the side of the head the phone is held during calls, and even to discontinuing mobile phone use. Lönn et al. (2004a), in their study of acoustic neu- roma, assessed impact of hearing loss and tin- nitus 5 years before reference date and reported no differences in risk estimates for patients with and without hearing loss. Whether this is an indication that such symptoms have no impact on mobile phone use and therefore do not bias risk estimates is difficult to assess because no data were reported. As noted by Schoemaker et al. (2005), 59% of regular phone users among controls reported predominantly right- sided use, 33% left-sided use, and 8% use on both sides. The authors argued that if mobile phones cause acoustic neuromas, one might expect a higher proportion of tumors on the right than on the left side of the head among regular phone users. However, this expectation is completely unfounded. In contrast, tumor growth may cause behavioral changes, as indi- cated by the distribution of mobile phone use in cases, with only 49% right-sided users, 40% left-sided users, and 11% that used the phone on both sides. Although response bias, misclassification bias, and insufficient correction of inter- view lag time between cases and controls will reduce risk estimates toward or even below unity, some biases could lead to a spuriously increased risk. One particular point has been raised frequently: Increased risk estimates of ipsilateral mobile phone use (Table 1) could be due to recall bias. If mobile phone use affects tumor development and growth, it is impor- tant to consider the side of the head to which the phone is held during calls. Cardis et al. (2008) reported that 97–99% of the total elec- tromagnetic energy deposited in the brain is absorbed at the side of the head the phone is held during calls. Because of this asymmetry, an effect at the site of the growing tumor is expected only or primarily for ipsilateral use. There is no objective method to retrospectively assess side of the head the phone has been used. Asking a person about this aspect of use could result in bias. A person may be inclined to suspect mobile phone use as a causal fac- tor and may therefore tend to report using it at the same side as the tumor has occurred. On the other hand, the reverse also may be claimed—that a person wants to dismiss the possibility that using the phone has anything to do with the disease and is therefore falsely ovlume 117 | number 3 | March 2009 • Environmental Health Perspectives