I was honored to be asked to contribute a chapter to the collected works within Tortured Science: Health Studies, Ethics and Nuclear Weapons in the United States, compiled and edited by Dianne Quigley, Amy Lowman, and Steve Wing, published 2012 by Baywood Publishing Company, Inc, Amityville, New York. I am very grateful that Baywood has allowed me to reprint the chapter in its entirety. The chapter is reprinted as a series of excerpts.
EXPERT REVIEW The Experts Look at What Went Wrong
The NRC Subcommittee concluded that while the study itself was well-
designed, HTDS scientists reported the study’s findings as more conclusive than they really were purported to be . “Shortcomings in the analytical and statistical methods used by the study’s investigators overestimated the ability to detect radiation effects, which means the study results are less definitive than had been reported” [57, p. 1].
There were several important reasons why the HTDS was limited in its ability to detect radiation effects. The NRC Subcommittee saw the study’s weakest link as the estimation of individual radiation doses from the 1940s and
1950s. The doses, which were being correlated to incidence of thyroid and parathyroid disease within the HTDS study group, were estimated based on assumptions about participants’ milk consumption, their mother’s milk con- sumption during periods when participants were breastfed, and the radioiodine levels of the milk and fresh food they consumed during the periods of greatest radioiodine releases from Hanford. These estimates depended on the accuracy of study participants’ (or other informants’) memories of the sources and quantity of milk intake decades in the past, as well as on estimates of how much radioiodine was released at specific times, where it was dispersed by wind and rain, how much was ingested or inhaled by dairy animals grazing on pasture or eating stored feed, and where the resulting milk (and other fresh food) was distributed . Since records about these factors were not collected at the time downwinders were exposed, researchers used mathematical models, which have large uncertainties, to estimate HTDS participants’ doses .
Computer-assisted telephone interviews (CATIs) were used within the HTDS to collect information about cohort members’ early dietary habits, including times and durations of breastfeeding period, if any. Many of the HTDS cohort members reported being breastfed for part of their infancy. But, for some 1,212 participants in the HTDS, for whom there was no CATI data, a default diet of cows’ milk was assigned. If any of these participants had actually consumed fresh sources of milk or breast milk, their doses could have been underestimated.
In addition, the technical review of the HTDS found evidence that the esti- mation of the amount of radioiodine that is passed into mothers’ milk (the milk transfer coefficient) assumed in the HEDR was underestimated. This would also lead to an underestimate of true dose for cohort members who were breastfed as infants—particularly those born in 1945, during the highest I-131 releases from Hanford [59, p. 8]. If a subgroup of the HTDS cohort, such as this subgroup, received systematic overestimation or underestimation of dose, this would diminish the ability of the study to detect a relationship between radioiodine and thyroid disease, and lead to an overestimation of the study’s ability to detect an effect.
Another possible explanation for uncertainty in dose estimates for HTDS cohort members is referred to as inter-individual stochastic variability. Some of the factors that may cause true dose to vary from the estimated dose include where the I-131 actually deposits, how much lands on vegetation, how much gets into the food chain, how much people actually ingested or inhaled, individual variation in size of the thyroid mass, and uptake from blood to the thyroid gland. Individual variability in dose estimates may also be influenced by radiosensitivity differences or intake levels of iodized table salt (consumption of iodized table salt may reduce the levels of radioiodine taken up by the thyroid), as well as other individual factors. HTDS researchers only considered some of these factors, but they may help explain why, on a street in my town of Richland, it was possible for two families to live the same length of time during the same period and be exposed to the same I-131 releases, yet one family developed thyroid disease and the family next door had no thyroid health impact at all.
The technical review of the HTDS also found that certain factors in the study led to an underestimation of uncertainty of HTDS doses which would contribute to lowering the statistical power of the HTDS [59, p. 9]. Overall, the NRC Subcommittee found that the statistical power of the HTDS to detect an associa- tion between radioiodine and thyroid disease was not as high as claimed by the HTDS researchers due to inadequate allowance for imprecision in the dose estimates [60, 61].
Another source of uncertainty in the HTDS cohort dose estimation arises from the fact that, during the 1950s and early 1960s, two other environmental sources of I-131 contributed to the thyroid doses received around Hanford. The first of these was fallout from nuclear weapons tests detonated at the Nevada Test Site (NTS) during the 1950s. The second source was fallout from nuclear weapons tests (“global fallout”) conducted by the United States and other countries outside of the U.S. mainland in the 1950s and 1960s, including Test Bravo in the Marshall Islands (1954), which deposited I-131 and other radionuclides within the Hanford downwind region. The issue raised by the NRC Subcommittee in its review of HTDS was that, if NTS or global fallout could have resulted in significant I-131 exposures in the HTDS study area, and if the variation within the area was large, then it was very important to take both global and NTS fallout into account in the HTDS [60, p. 8]. Rather, the HTDS analysis of NTS I-131 doses was based upon a median dose for all subjects, causing them to be essentially disregarded . The expert review concluded that HTDS could not rule out the possibility that dose-response relationships were actually present, but not able to be seen due to the fact that these confounding exposures from global and NTS fallout were not explored thoroughly [62, p. 11]. The uncertainty in dose due to the fact that doses were, of necessity, modeled and possibly confounded by global and NTS fallout, should have been communicated at the HTDS public briefing on January 28, 1999.
In a letter transmitted to the CDC just 10 days before HTDS results were made public, the NRC Committee on the Assessment of CDC’s Radiation studies raised and emphasized problems with the uncertainties of individual doses calculated with the HEDR methods used in conjunction with the HTDS:
It should be noted that the inherent uncertainty associated with the indi- vidual doses will decrease the likelihood of determining a meaningful risk coefficient for the effects of radioiodine on the target population .
Scott Davis, the principal HTDS investigator, is reported to have said that “he couldn’t agree more” that there should have been a more thorough scientific review of the study before it was released . A citizens’ letter to the director of the NCEH stated, “It is appalling that CDC would go forward with the release of the HTDS under such circumstances, and so quickly after its NRC review committee had identified such major problems” .
56. The National Academy of Science’s National Research Council (NRC) Subcommittee of the Board on Radiation Effects Research released the results of its extended review of the draft final HTDS report on 12 December 1999 in a public meeting in Spokane, Washington
57. NAS review report. 14 December 1999, p. 1.
58. The milk pathway is one of the primary means by which radioiodine is ingested, and is a particular concern with infants and children. The radioiodine deposits on pasture grass, the cows or goats eat the contaminated grass, and then the radioiodine is ingested by humans as the milk is consumed. A child’s thyroid uptakes far more radioiodine than an adult’s thyroid. This is because children often consume a greater quantity of milk than adults, because their thyroids are smaller and more vulnerable than those of adults, and because of a faster metabolism than that of adults.
59. See Ruttenber, A. J., et al. 30 March 2004. A technical review of the final report of the Hanford Thyroid Disease Study. p. 3, citing Hoffman 1991, Hoffman et al., 1993, Hoffman et al., 1996, Hoffman 1999. Prepared as an expert report for the Hanford litigation, to respond to suggestions and recommendations of the NRC Subcom- mittee’s 2002 Hanford Thyroid Disease Study Draft Final Report. See also Hoffman, F. O., Ruttenber, A. J., Apostoaei, A. L., Carroll, R. J., and Greenland, S. 2007. The Hanford Thyroid Disease Study: An alternative view of the findings. Health Physics Journal 92(2):99-111.
a. HTDS results do not show statistically significant elevations in risk but are not inconsistent with other published studies supporting risks for certain thyroid diseases from I-131 exposures, if the upper bounds of the calculated confidence intervals are considered (as pointed out for the situation of thyroid cancer and I-131 exposure from NTS fallout by the NRC). [emphasis added]
b. Applying a strict interpretation of the lack of statistical significance found in the results of HTDS, we find that the results of HTDS are consistent with the finding of thyroid risk in some but not all studies of I-131 exposures, but not consistent with those studies which show elevated thyroid risk, or;
c. If the results are subjected to strict interpretation based upon statistical signifi- cance, then HTDS is not inconsistent with other studies which show that chronic exposure to I-131 is not associated with thyroid disease.
60. NAS-BRER. 2000. Review of the Hanford Thyroid Disease Study draft final report.
Washington, DC: National Academy Press, p. 7.
61. Ruttenber, A. J., et al. 30 March 2004. A technical review of the final report of the Hanford Thyroid Disease Study. p. 3 See also Hoffman, F. O., Ruttenber, A. J., Apostoaei, A. L., Carroll, R. J., and Greenland, S. Feb. 2007. The Hanford Thyroid Disease Study: An alternative view of the findings. Health Physics Journal 92(2):
62. Instead, only NTS fallout was taken into account within HTDS. Doses were divided into two parts based on the median dose for all subjects (5.3 mGy) and then put through simple analysis as a confounder or effect modifier in dose-response models. These simple analyses caused HTDS authors to conclude that NTS fallout doses were not confounders or effect modifiers in any model, and so could be disregarded. The expert panel found that, for people who consumed fresh milk, the cut-off dose utilized for NTS fallout I-131 exposures within HTDS appeared to be very low and relevant only to people who did not consume fresh milk. Use of the National Cancer Institute’s online I-131 NTS fallout dose calculator http://ntsi131.nci.nih.gov/ shows, for counties included in HTDS, that typical NTS doses from drinking fresh milk are much higher than 5.3 mGy. For those individuals who had not consumed any milk at all, other milk consumption scenarios reveal NTS I-131 doses which were substantially higher than the 5.3 mGy assigned within HTDS. 1,616 of the HTDS participants were assigned NTS I-131 doses of less than 5.3 mGy by HTDS researchers. Because only 8 percent of HTDS participants reported no consumption of raw or processed milk products, it was not reasonable that 1,616 participants would have NTS doses less than 5.3 mGy. “Therefore, it appears that the NTS doses calculated for members of the HTDS cohort have been underestimated.” Ruttenber, A. J., et al. 30 March 2004. A technical review of the final report of the Hanford Thyroid Disease Study, p. 9.
63. See Commission on Life Sciences. 1998. Letter report-review of analysis plan for the Hanford Thyroid Disease Study (HTDS). National Academies of Science.
64. Fallout from thyroid study: Critics fault CDC for early, unreviewed results.
Spokesman Review, 19 February 1999.
65. Letter of 18 February 1999 to Dr. Dick Jackson, then Director of NCEH, re: problems with HTDS, signed by more than 22 citizen groups.