A Review of the Draft Report of the NCI-CDC Working Group to Revise the 1985 Radioepidemiological Tables (2000) / Chapter Skim
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Contents of Report
Contents of Report
Pages 3-35
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to review the draft report of the National Cancer Institute (NCI) CDC's working group charged with revising the 1985 radioepidemiological tables.
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The working group has used a systematic approach to analyze radiation effects identified in studies of the Japanese survivors of atomic bombs; so risk estimates for the various tumor sites should be comparable. It has also provided broad coverage of tumor sites, so its draft report and the accompanying computer program are widely applicable.
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Data Sources for Estimates of Uncertainties The working group based its evaluation of uncertainty in radiation risk coefficients and models primarily on analyses of data that have been conducted with the studies of the Japanese survivors of atomic bombs. For specific cancer types the working group evaluated uncertainty distributions by sex, age-at-exposure, time-after-exposure, and age-at-observation.
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The large uncertainty factors used for the RBE values are appropriate, given the diverse results found in experimental studies. The transfer of radiation risks from the Japanese population to the US population was handled by Monte Cario simulation to determine the average of the risks derived with additive and multiplicative models.
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A variety of experimental and epidemiologic data on low-LET radiation indicate that the risk posed by highly fractionated or protracted exposures is not greater than, and even tends to be less than, that posed by an acute exposure of the same total magnitude. The subcommittee therefore agrees that the assumption of additivity is reasonable and that there is no need to build into the mode} a potentiation of effects by serial exposures.
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The subcommittee believes that for the major cancer sites, the working group has struck a sensible balance allowing for some differences between cancer sites but not subdividing the data more finely than is warranted. In the case of some of the rarer sites, however estimates for groups of sites might be more reliable, barring convincing evidence that the sites really are different.
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6. APPLICABILITY OF ASSIGNED SHARE CALCULATIONS TO MINORITY GROUPS The working group's draft report gives little consideration to the appropriateness of AS calculations to minority groups, nor does it provide an alternative for cases in which the baseline rates of particular cancers differ appreciably between specific minority groups and the average population.
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This comparison should also include some discussion of where the two sets of tables differ most. In the original tables, the authors identified a series of parameters to which they assigned uncertainty distributions: baseline values, influence of age-at-exposure, time-since-exposure, ratio of linear coefficients in the linear and linear-quadratic dose-response models, latent penod, and risk coefficients.
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As stated in both the 1985 report and 2000 draft report, many other aspects of uncertainty are not included and are likely to give rise to additional uncertainty. Both the method used by the working group and the one suggested above assume that all parameter uncertainty distributions are independent (uncorrelated)
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In place of the current general scale factor, we recommend an option to enable users to include a factor in addition to those explicitly stated, provided that they specify a name and a distribution. To implement that option, the general scale factor should be renamed "additional uncertainty factor", its default GSD should be set to 1.0 so that it will have no effect unless altered by the user, and a user who wishes to include this factor, should first have to specify a name for the uncertainty distribution (that is, identify specifically what variation the factor represents)
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As work progressed, however, it became apparent that an alternative existed to develop an interactive computer program that would make it easier for a potential user to calculate the risk to an individual, assuming the user has sufficient information at hand. The working group chose this alternative, and the result is an application for the personal computer the Interactive Radio-Epidemiological Program (IREP)
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One unnecessary restraint on system access is how identification information and other personal information are collected by the system. This may be of concern to potential users, particularly if a Web-based implementation is chosen.
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. Distribution form and parameters for errors in dosimetry (see page 32 of working group's draft report)
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The default is set at 1,000, which does not yield particularly stable predictions of the 99th percentile AS value in repeated runs for at least some cancer sites (a lO-fold increase in sample size yielded increased stability, albeit at a substantial cost in processing time)
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denies more people compensation, this situation must be acknowledged in a public summary, and the factors causing the increased claim denials should be explained. If care is not taken, using the IREP might create serious risk communication problems for the VA, with the agency being accused of applying it only to save money and not to assist veterans.
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In addition to the Web site, however, the subcommittee recommends that a printed public summary be available to potential users and family members who do not have ready access to computers and the Internet. The question of computer accessibility also comes up for members of lower economic and minority groups.
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, one would fit a broad suite of alternative models and report a weighted average of their predictions weighted by their respective posterior probabilities. This approach has the appealing feature of providing confidence limits that reflect the uncertainty about true model form.
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Therefore, the committee recommended the use of the term assigned share for this quantity, and this recommendation was adopted by the working group in the current revision. One of the reasons the National Research Council Oversight Committee chose assigned share over probability of causation was the possibility of a hazard ratio less than one.
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The subcommittee is therefore persuaded that the AS approach still has some validity, at least for relative ranking of claimants. A number of authors, including the 1984 National Research Council Oversight Committee, have pointed out various inequities that can arise in a compensation scheme that provides All 21
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. For such reasons as those, alternative compensation schemes have been proposed, most based on some kind of sliding scale in which the amount of compensation awarded depends on the magnitude of the estimated PC or on the uncertainty distribution of the PC estimates.
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As to compensation, some agencies, such as the VA, recognizing uncertainty' have used an upper confidence limit on AS (the 99th percentile in the VA) as a screening criterion to weed out claims that have little chance of being successful.
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In large part, this has already been done by the working group and the various authoritative bodies on which its estimates are based. With regard to the large number of cancer sites where no statistically significant doseresponse relationship has been identified, the subcommittee notes that inclusion of these tumors constitutes a large departure from the i985 tables, which considered only sites with a statistically 24
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Assuming that the 95% confidence intervals presented in table X have a length of roughly 4 standard errors (which is true asymptotically) , we estimated the standard errors of the risk for the various sites.
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Nevertheless, we fee} that it is important in the case of rare tumors for the data on specific sites to be supplemented by what is known about other sites, and we believe that a random-effects analysis provides a reasonable, albeit largely pragmatic general framework. Accordingly, we suggest that the Working Group consider a hybrid analysis conducted as follows: a single summary ERR risk estimate for each of the nonradiogenic-cancer sites should be prepared as in table X of Thompson et al.
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A module for computing ASs for lung cancer in radon-exposed people would be a valuable addition, as opposed to waiting for the next update. The basis of the uncertainty distributions for the DDREF should be described and justified.
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The working group should consider how to transport PC calculations to minority populations in the United States when minority group's baseline rates differ appreciably from the average US rates. In principle, this is similar to the problem of transporting risk estimates from the Japanese to the US population.
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The subcommittee recommends that AS calculations be performed for nonmelanoma skin cancers; information regarding the baseline rates in the United States is needed to use the transportation algorithm described in the working group's report. These skin cancers are not reportable in the United States, so routine SEER data are unavailable; but various surveys provide sufficient information for transportation (perhaps incorporating uncertainty into the baseline US rates)
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Therefore, even if point estimates were large enough to suggest an important effect, the confidence intervals were so broad because of sample size that the effect was not significant. A result that is not statistically significant can be interpreted inappropriately as evidence of no effect.
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. To elucidate the differences in the estimated AS values in the current working group's draft report from the 1985 report, the subcommittee recommends that a more extensive comparative analysis of the IREP program output be conducted than has been done for the current draft report.
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. To evaluate the importance of cancer sites for which the number of events is relatively rare, the subcommittee suggested above that future evaluations use either hierarchic randomeffects models or Bayes mode!
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. The current draft report, although adequate for a technical audience, will need modification for other constituencies.
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Here the subcommittee is not suggesting the 50°/0 probability as a "bright line" cutoff, but rather the award of compensation on a sliding scale depending on the posterior probability that the PC exceeds 50°/O, on the bases of its uncertainty distribution. · Theoretical arguments have demonstrated that unobservable heterogeneity between individuals can lead to a downward bias in the epidemiolog~cally derived AS as an estimator of the average of individuals' PCs and that the magnitude of this bias will vary across individuals in a way that depends on such factors as age, dose, and unobservable baseline risk.
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In other words, the subcommittee does not advocate a specific compensation system, but suggests that agencies involved in compensation claims review the systems that they use to avoid inequities in their procedures.
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