eTable 1. Overall cancer risk from use of potentially NDMA-contaminated valsartan drug products compared with uncontaminated valsartan.
| Hazard ratio [95% CI]*1 | Sample size/ cancer cases | |
| Exposure to NDMA-contaminated valsartan | ||
| No exposure | 1.00 (ref) | 371 688/17 504 |
| Exposure | 1.00 [0.98; 1.02] | 409 183/24 752 |
| Exposure in dose categories | ||
| 0 to ≤ 90 DDDs | 1.00 [0.97; 1.03] | 130 684/8449 |
| > 90 to ≤ 170 DDDs | 1.01 [0.99; 1.04] | 144 876/8390 |
| > 170 DDDs | 0.98 [0.95; 1.00] | 133 623/7913 |
| NDMA exposure | ||
| Possible NDMA exposure (contaminated valsartan batches <75%) | 1.00 [0.97; 1.03] | 111 962/7761 |
| Probable NDMA exposure (contaminated valsartan batches >=75%) | 0.99 [0.97; 1.02] | 297 221/16 991 |
| Only prevalent valsartan use*2 | ||
| No exposure | 1.00 (ref) | 71 318/5754 |
| Exposure | 0.97 [0.94; 1.01] | 175 034/12 464 |
| Only incident valsartan use*2 | ||
| No exposure | 1.00 (ref) | 300 370/11 750 |
| Exposure | 1.01 [0.98; 1.04] | 234 149/12 288 |
| Long-term valsartan use*3 | ||
| No exposure | 1.00 (ref) | 64 836/3472 |
| Exposure | 0.96 [0.89; 1.04] | 14 686/817 |
| Exposure in dose categories | ||
| 0 to ≤ 90 DDDs | 1.00 [0.86; 1.17] | 2629/166 |
| > 90 to ≤ 170 DDDs | 1.03 [0.89; 1.18] | 3777/220 |
| > 170 DDDs | 0.91 [0.83; 1.01] | 8280/431 |
| Incidence rate*4 per 100 000 persons | ||
| No exposure | 1254.71 | |
| Exposure | 1270.30 | |
*1 Lag time 1 year, fully adjusted for sex; age; polypharmacy (defined as prescription of five or more different drugs); prescription of low-dose acetylsalicylic acid (ASA), non-ASA non-steroidal anti-inflammatory drugs, 5α-reductase inhibitors, statins, spironolactone, glucocorticoids for systemic use, selective serotonin reuptake inhibitors, and hormone replacement therapy; the comorbidities diabetes, chronic obstructive pulmonary disease, congestive heart failure, and alcohol-related diseases; the Charlson comorbidity index (score); and prevalent valsartan use
*2 Without covariate “prevalent valsartan use”
*3 Long-term valsartan use is defined as valsartan prescription in at least nine quarters within the first 3 years of the study period.
*4 Standardized to the German population over 40 years in 2011 (e2)
DDD, defined daily dose; NDMA, N-nitrosodimethylamine; 95% CI, 95% confidence interval