Table 1.
Characteristics of the Included Studies in the Scoping Review for the State of Use and Utility of Negative Controls in Pharmacoepidemiologic Studies
| Characteristic | Study (n = 184) | |
|---|---|---|
| No. | % | |
| Publication year | ||
| Before 2012 | 12 | 6.5 |
| 2013–2016 | 46 | 25.0 |
| 2017–2020 | 126 | 68.5 |
| Study region | ||
| North America | 94 | 51.1 |
| Europe | 61 | 33.2 |
| Asia | 13 | 7.1 |
| Others | 4 | 2.2 |
| Multiple regions (including more than 1 continent) | 12 | 6.4 |
| Study design | ||
| Cohort study | 115 | 62.5 |
| Case-control study | 12 | 6.5 |
| Self-controlled case series | 9 | 4.9 |
| Nested case-control study | 7 | 3.8 |
| Ecological study | 5 | 2.7 |
| Self-controlled cohort study | 2 | 1.1 |
| Case-crossover study | 1 | 0.5 |
| Cross-sectional study | 1 | 0.5 |
| Self-controlled risk interval study | 1 | 0.5 |
| Pharmacovigilance study | ||
| Disproportionality analysis | 4 | 2.2 |
| Sequence symmetry analysis | 3 | 1.6 |
| Sequential statistical testing | 3 | 1.6 |
| Multiple studies with different designs/methods | 14 | 7.6 |
| Reference set identification | 5 | 2.7 |
| Others | 2 | 1.1 |
| Type of NC | ||
| NCE | 54 | 29.3 |
| NCO | 91 | 49.5 |
| Both NCE and NCO | 34 | 18.5 |
| Not applicablea | 5 | 2.7 |
| No. of NCs used | ||
| Single (either NCE or NCO) | 84 | 45.7 |
| Multiple | 94 | 51.0 |
| Not applicablea/not reported | 6 | 3.3 |
| Type of biasb | ||
| Unmeasured confounding | 93 | 50.5 |
| Information bias (e.g., misclassification, measurement error) | 10 | 5.4 |
| Selection bias | 7 | 3.8 |
| Protopathic bias | 2 | 1.1 |
| Bias in general/not specified | 80 | 43.5 |
| Type of data source usedb | ||
| Health-care administrative data (e.g., insurance claims, national health system data) | 114 | 62.0 |
| Electronic health records | 61 | 33.2 |
| Research data (e.g., primary data) | 26 | 14.1 |
| Disease registry | 11 | 6.0 |
| Passive surveillance data for drug safety | 7 | 3.8 |
| Simulated data set | 6 | 3.3 |
| Public health survey data | 4 | 2.2 |
| Not applicablea | 5 | 2.7 |
Abbreviations: NC, negative control; NCE, negative control exposure; NCO, negative control outcome.
a Reference set identification studies with no empirical application of NC.
b Categories are not mutually exclusive.