TABLE 5.

Strengths and Limitations of Included Papers

Brief description	Source (Ref.)	Strengths	Limitations
Sellafield Females	McGeoghegan et al. 2003 (29)	● Comprehensive identification of subjects with limited loss to follow-up; ● Organ doses calculated for plutonium exposures; ● Exposure assessment comprehensive, including external doses, plutonium uptake, and doses from other facilities	● Uncertainties in film badge dose quality; ● No attempts to control for SES
Male Colorado Plateau Millers	Pinkerton et al. 2004 (30)	● Comprehensive identification of subjects; ● Comprehensive SMR/SIR analyses with sensitivity analyses	● No dosimetry; ● No control for SES or lifestyle confounding in SMR/SIR analyses
French Nuclear Workers (CEA & AREVA)	Telle-Lamberton 2007 (31)	● Comprehensive identification of subjects with limited loss to follow-up; ● Efforts to control for confounding through stratification; ● Comprehensive individual dosimetry, assessed for accuracy	● No mortality information before 1968; ● Organ doses were not calculated; ● Excluded workers employed at both sites due to lack of dose reconstruction
15-Country Study	Vrijheid et al. 2007 (32)	● Large effort for dosimetric accuracy across cohorts; ● Organ doses calculated and utilized	● Potential residual confounding by socioeconomic status, and loss of power and accuracy by excluding entire sites where socioeconomic status was not recorded; ● Dosimetric inaccuracies in Canadian data biased estimates; ● Other known sources of potential confounding, such as smoking
Grants Miners and Millers	Boice et al. 2008 (33)	● Comprehensive identification of subjects from multiple record sources; ● Efforts to control confounding through stratification	● No dosimetry; classification only by whether there was potential exposure to radon underground; ● Early deaths excluded because NDI records were not available; ● Low-power cohort
Male British Nuclear Fuels Workers	McGeoghegan et al. 2008 (34)	● Attempts to control for SES and other potential confounders; ● Individual monitoring at the site of interest	● Only cumulative external absorbed dose was calculated, with a flag for internal exposures; ● Noted considerable inhomogeneity over worker type that may be attributable to inaccurate dosimetry or residual confounding; ● Exploratory analyses determined Poisson models of interest
French Nuclear Contract Workers	Guerin et al. 2009 (35)	● Expanded cohort considerably from the last iteration; considerable effort placed into identifying missing individuals; ● Comprehensive, individual dose monitoring and exposure assessment, including all relevant sources on site	● Missingness in the overall cohort since contracting companies did not always have employee details; ● Low power since ~97.5% of contractors were still alive at the end of follow-up; ● Missing job type in 56% of workers; ● Their ERR analysis uses SMR as the dependent variable
French Nuclear Fuel Company Cohort	Metz-Flamant 2009 (36)	● Comprehensive identification of subjects with limited loss to follow-up; ● Efforts to control for confounding through stratification; ● Comprehensive individual dosimetry, assessed for accuracy	● Organ doses were not calculated; ● No dosimetry for internal doses, despite known exposures in some individuals
British National Registry for Nuclear Workers	Muirhead et al. 2009 (37)	● Comprehensive identification of subjects with limited loss to follow-up; ● Fairly direct control for socioeconomic status; ● Good registry data for disease incidence and mortality	● Organ doses were not calculated; ● No dosimetry for internal doses, despite known exposures in some individuals; ● Different inclusion criteria for sites within the overall study
Colorado Plateau Miners	Schubauer-Berigan et al. 2009 (38)	● Comprehensive individual dosimetry with efforts made to assess accuracy; ● Smoking surveys were conducted, so smoking was included in the analysis	● Potential problems in the assumptions underlying interpolation used for calculating daily dose-rates; ● Potential unadjusted confounding from a variety of sources
French Uranium Processing Workers	Guseva Canu et al. 2010 (39)	● Comprehensive identification of subjects with no loss to follow-up; ● Comprehensive mortality information; ● Sensitivity analyses used regional background population for SMRs	● Study focus was internal exposures, yet no internal dosimetry was available; ● Organ doses not calculated
Eldorado Workers	Lane et al. 2010 (40)	● Demonstrated effort to trace individuals who were missing data in the cohort; ● Efficient use of existing data to retain individuals in the study when other data was unavailable	● Dosimetry is predominantly retrospective dose reconstruction from uncertain area data across the cohorts included in the study; ● Sensitivity analyses were only conducted for lung cancer models (NMRD not included); ● No adjustment for SES or lifestyle variables
French Electric Company Staff	Laurent et al. 2010 (41)	● Comprehensive individual dosimetry, assessed for accuracy; ● Assessed a 1% sample of the cohort for dosimetric accuracy between two extant databases; ● Detailed dose data for relevant organs used in analysis; ● Attempts to control for confounding, including SES	● Uncertainty due to different film badge calibrations harmonized over time; ● Used a flag for neutron dose instead of calculating organ dose; ● Missing lifestyle confounders
Sellafield Windscale Accident Workers	McGeoghegan et al. 2010 (42)	● Comprehensive identification of subjects with limited loss to follow-up; ● Comprehensive outcome data from registries and with validation; ● Adjustments made for various factors including socioeconomic status	● Fire cohort workers (population of interest) included non-radiation workers, but non-fire cohort workers (comparison population) excluded non-radiation workers; ● No internal dosimetry conducted; ● Low powered analysis
Rocketdyne Workers	Boice et al, 2011 (43)	● Very thorough dosimetry, accounting for 14 radionuclides in 16 organs; ● Minimal loss to follow-up; ● High ascertainment of underlying cause of death; ● Attempts to approximate and validate approximation of missing potential confounders	● Dose uncertainty, particularly at low levels; ● No sensitivity analyses; ● Relatively small study; low statistical power; ● No lifestyle information
Male Wismut Miners	Kreuzer et al. 2013 (44)	● Thorough radon dose reconstruction; ● Multiple sensitivity analyses to assess various sources of potential bias; ● High statistical power in a large cohort	● No individual dosimetry; ● No adjustment of SES or lifestyle factors; job type used in dose reconstruction; ● No assessment of external dose
Fernald Workers	Silver et al. 2013 (45)	● Quantitative assessments of a variety of exposures including external dose, uranium intake, radon decay products, and thorium (flag); ● Organ doses calculated for uranium intake; ● Adjustments made for non-radiologic covariates in analyses; ● Attempts to control for confounding by SES and other confounders	● Information lacking for lifestyle confounders; ● Dose cut-points for analyses differ by outcome with no explanation in text
Male Port Hope Workers	Zablotska et al. 2013 (46)	● Registry-based follow-up assessed for accuracy; recoded where necessary; ● Sensitivity analyses addressing particular points of uncertainty	● No dose data was available; doses were reconstructed based on uncertain area monitoring data; ● Organ doses were not calculated; ● No adjustment for SES or lifestyle factors
Male German Uranium Non-Miners	Kreuzer et al. 2015 (47)	● Good discussion of correlation of different exposures, justifying some of their dose reconstruction	● Potential differential completeness of participant selection by level of dose; ● Considerable uncertainty in organ dose estimates due to lack of dosimeters until the 1990s; ● Rather small range of doses; low power; ● Potential cause of death ascertainment different by exposure; ● Missing outcome information for nearly half of the deaths prior to 1970; ● Few confounders included
Male French Atomic Energy Commission Miners	Rage et al. 2015 (48)	● Used a post-1955 cohort to assess the period in which everyone was individually monitored for external exposures, radon, and long-lived radionuclides; ● Systematic and unbiased exposure assessment; ● Smoking assessed in a sub-cohort using a nested case-control study	● No dosimeters issued before 1955; uncertainty in full cohort; ● Missing data on confounders including SES, lifestyle factors, and other toxins in the workplace; ● P-value based reporting and decision-making; switching between 90 and 95% confidence intervals to report results
TRACY Cohort	Samson et al. 2016 (49)	● Strong set of sensitivity analyses	● No dosimetry in this cohort yet; ● Missing data on confounders; no attempt to address SES; ● Low statistical power
French Uranium Enrichment Workers	Zhivin et al. 2016 (50)	● Considerable effort creating job exposure matrices to construct exposure quantiles for uranium exposure; ● Comprehensive identification of subjects with limited loss to follow-up; ● Information available on confounding exposures (though not used in NMRD analyses)	● Confounders not included in models because instability (likely low power); ● ERRs estimated below zero with lower bounds that could not be estimated below zero; ● Dosimetry limited to exposure quantiles, despite detailed JEM and good external information
INWORKS	Gillies et al. 2017 (6)	● Large, comprehensive study; ● Large effort for accuracy in dosimetry; ● Tests to determine whether smoking was a potential confounder; indication that it is not	● Tissue-weighted doses rather than organ doses; ● Assessment does not include all relevant periods of exposure (French cohort truncation); ● Removing French data resulted in changes to significance despite the French component being the smallest; ● ‘‘Missed’’ doses in early periods lead to uncertainty
French Cohort of Nuclear Workers	Leuraud et al. 2017 (51)	● Comprehensive identification of subjects with limited loss to follow-up; ● Detailed and validated external dosimetry, with sensitivity analyses for absent neutron and internal radionuclide information; ● Sensitivity analyses conducted to assess bias	● No mortality information before 1968, workers excluded who were deceased before this date; ● Organ doses were not calculated; ● Different dates of follow-up for different cohorts
US Uranium Gaseous Diffusion Workers	Yiin et al. 2017 (52)	● Detailed internal and external dosimetry with calculated organ doses; ● Calculated exposures to nickel and trichloroethylene assessed as confounders in analyses; ● Comprehensive identification of subjects with limited loss to follow-up	● Doses from other facilities not included in total dose; ● Uncertainty associated with intake and dose calculations not included in epidemiological analyses; ● No attempted assessment of socioeconomic status
F-Millers Cohort	Bouet et al. 2018 (53)	Very low loss to follow-up (<1%); ● Efforts to control for confounding through stratification	● No dosimetry; ● No mortality information before 1968
Male French Miners plus Jouac	Rage et al. 2018 (54)	● Dose-response analysis of radon exposure; ● Inclusion of more information into an existing mining cohort	● Jouac exposure information only available post-1977 (cohort began in 1957); ● Analyses only considered radon exposure, and not uranium, long-lived radionuclides, or gamma exposures; ● Analyses did not consider socioeconomic status
Canadian and German Uranium Processing Workers	Zablotska et al. 2018 (55)	● Retrospectively reconstructed dosimetry that took considerable effort; ● Pooled cohort increases power; ● Detailed confounding and effect modification assessment	● Dosimetric uncertainties in dose estimation; ● No information on socioeconomic status; ● Different inclusion criteria for Port Hope vs. Wismut
French Nuclear Fuel Production Workers	Bouet et al. 2019 (56)	● Comprehensive identification of subjects with limited loss to follow-up; ● Extensive external and internal dosimetry, with organ doses for internal dosimetry; ● Adjustments for potential confounders, including socioeconomic status	● Uncertainties in dosimetry; a subcohort of the TRACY study was used as information is not yet computerized for the full cohort; ● No mortality information before 1968, workers excluded who were deceased before this date; ● Many models did not converge due to low numbers of outcomes
Male Mallinckrodt Workers	Golden et al. 2019 (57)	● Dose reconstruction including external, internal, and medical X-ray irradiation, and doses from sites other than Mallinckrodt; ● Comprehensive identification of subjects with limited loss to follow-up; ● Controlled for confounders such as silica dust and socioeconomic status	● Low power due to a small number of individuals and low doses; ● Uncontrolled confounding for other exposures experienced at Mallinckrodt (solvents, etc.); ● Some dosimetric uncertainty, specifically from imputed doses
Czech Republic Uranium Miners	Kelly-Reif et al. 2019 (58)	● Comprehensive identification of subjects; ● Causal mortality rates present an interesting way to view years of life lost	● No dosimetry conducted; ● Only workers alive and already in the cohort in 1977 were included since the Czech cancer registry began in 1977; potential survivorship bias; ● Residual confounding/bias likely