| Trial | HIP19 | CNBSS-113 | CNBSS-213,20 | Edinburgh18 | Gothenburg14,23 | Stockholm17 | Malmö25 | Swedish 2-County Trial16 | |
|---|---|---|---|---|---|---|---|---|---|
| Description | |||||||||
| Year study began | 1963 | 1980 | 1980 | 1978 | 1982 | 1981 | 1976-1978 | 1977 | |
| Setting/Population | New York health plan members | 15 centers in Canada, self-selected subjects | 15 centers in Canada, self-selected subjects | All women aged 45-64 from 87 general practices in Edinburgh | Entire female population, born between 1923-1944, of one Swedish town | Residents of southeast greater Stockholm, Sweden | All women born between 1927-1945 living Malmö, Sweden | From Ostergotland (E-County) and Kopparberg (W-County) | |
| Age at enrollment (years) | 40-64 | 40-49 | 50-59 | 45-64 | 39-59 | 40-64 | 45-70 | 40-74 | |
| Interventions | |||||||||
| Method of randomization | Age- and family size-stratified pairs of women randomized assigned individually by drawing from a list | Blocks (stratified by center and 5-year age group) after CBE | Cluster, based on general practitioner practices | Cluster, based on day of birth for 1923-1935 cohort (18%), by individual for 1936-1944 cohort (82%) | Individual, by day of month; ratio of screening to control group, 2:1 | Individual, within birth year | Cluster, based on geographic units; blocks designed to be demographically homogeneous | ||
| Study Groups | Mammography + CBE vs usual care | Mammography + CBE vs usual care (all women prescreened and instructed in BSE) | Mammography + CBE vs CBE (all women prescreened and instructed in BSE) | Mammography + CBE vs usual care | Mammography vs usual care; controls offered screening after year 5, completed screening at approximately year 7 | Mammography vs usual care; controls offered screening after year 5 | Mammography vs usual care; controls offered screening after year 14 | Mammography vs usual care; controls offered screening after year 7 | |
| Screening Protocol | Interval (months) | 12 | 12 | 12 | 24 | 18 | 24-28 | 18-24 | 24-33 |
| Rounds (n) | 4 | 4-5 | 4-5 | 4 | 5 | 2 | 9 | 3 | |
| Views (n) | 2 | 2 | 2 | 2 (1) | 2 (1) | 1 | 2 (1) | 1 | |
| Subjects (n) | |||||||||
| Study group | 30,239 | 25,214 | 19,711 | 28,628 | 20,724 | 40,318 | 21,088 | 77,080 | |
| Control group | 30,256 | 25,216 | 19,694 | 26,015 | 28,809 | 19,943 | 21,195 | 55,985 | |
| Longest followup by 2002 (years) | 18 | 13 | 13 | 14 | 12a | 11.4a | 11-13 15.5a |
20 15.5a |
|
| Trial | Trial Quality | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| HIP19 | CNBSS-113 | CNBSS-213,20 | Edinburgh18 | Gothenburg14,23 | Stockholm17 | Malmö25 | Swedish 2-County Trial16 | |||
| Assembly of comparable groups | Allocation concealment and baseline groups | Use of lists and pairs made subversion possible. More menopausal women and women with previous breast lumps in a sample of controls; more education in the screened group | Use of lists and blocks made subversion possible. In mammography arm, 17 had tumors with 4 nodes with initial screening vs 5 in control arm. | Use of lists and blocks made subversion possible | Allocation concealment not described. Significantly lower SES and higher all cause mortality in control group suggest inadequate randomization | Allocation concealment not described | Allocation concealment not described | Allocation concealment not described | Allocation concealment not described; intervention women slightly older than controls | |
| All cause mortality relative risk (screened vs control group) | 0.98 | 1.02 | 1.06 | 0.8 (statistically significant) | 0.98 | NR | 0.99 | 1 | ||
| Maintenance of comparable groups | Screening attendance. Round |
1 2 3 4 | 1 2,4 | 1 2 5 | 1 7 | 1 2-5 control | 1 2 control | 1 2-5 control | 1 2 3 control | |
| Screening attendance. % | 67 54 50 46 | 100 85-89 | 100 90.4 86.5 | 61 44 | 85 75-78 66 | 81 81 77 | 74 70 ??? | 89 83 84 ??? | ||
| Contamination (%) | Unknown, probably small | 25 | 16 | NR | 20 | NR | 25 | 13 | ||
| Post-randomization exclusions | Yes | No | No | Yes | One fewer death in screening group included in 1997 results | Yes | Yes | Yes | ||
| Validity of outcome assessment | Deaths included in analysis (followup vs evaluation method) | Breast cancer deaths diagnosed within 7 years of followup | Followup method | Followup method | Followup method and evaluation method | Initially, all four Swedish trials used the evaluation method of analysis (breast cancer cases diagnosed after screening period were excluded from count of breast cancer deaths), but this was corrected in re-analyses of the data in 1993 and in 2002. Control screening was delayed relative to the last screen in the mammography groups, resulting in bias because more cases of cancer were included in the control groups than in the intervention groups. | ||||
| Method for verifying breast cancer deaths | Blinded review of the death certificate and medical records; unclear how deaths were selected for review | Blinded review of all deaths of women known to have breast cancer whose death certificate mentions liver, lung, colon cancer, or unknown primary, or whose medical record raised a question of breast cancer | All deaths with breast cancer deaths diagnosed within 14 years of followup; not masked | In the 1993 analysis, an independent panel used an explicit protocol to preform blinded assessment of cause of death. | ||||||
| Analysis method | Intention-to-treat analysis; completeness of reportingb | Did not provide relative risk, confidence intervals, or P values in recent report; estimated the number of subjects | Appropriate | Appropriate | - | In all the Swedish trials, sample sizes differed for different publications because different methods were used to estimate the size of the underlying population. | ||||
| External validity | Comment | Poor mammography technique; only a third of cancer cases found by mammography alone | Many women with screening abnormalities (especially CBE) were "deemed not to require a diagnostic procedure," potentially reducing the sensitivity of screening | - | 19% of controls and 13% of study women had mammography in the 2 years before the study | 25% of all women entering the study had a mammogram before to entering the study | - | In the age group of 40-49 years, 3 women died after being invited to screening and 1 died before invitation but after randomization | ||
| Grade | USPSTF Internal Validity | Fair | Fair or better | Fair or better | Poor | Fair | Fair | Fair | Fair | |
aMost recent results for age 40-49, if different.
bAll studies were analyzed using intention-to-treat methods.
Note: Italics indicate aspects of the design or conduct of trials that influenced the quality rating.
BSE indicates breast self-examination; CBE, clinical breast examination; CNBSS, Canadian National Breast Screening Study; HIP, Health Insurance
Plan of Greater New York; NR, not reported; USPSTF, U.S. Preventive Services Task Force.