Table 1.
Summary of analytic techniques that can address immortal time, using surgical resection among women with metastatic breast cancer as an example.
| Analytic approach | Description | Interpretation |
|---|---|---|
| Time-varying exposure (yes/no surgery) (3, 4), ever/never treated | Included: All women with metastatic cancer | Effect of ever undergoing resection, compared to never, on mortality. |
| Treatment status: Surgical resection during any point during follow-up. Women are classified as being ‘unexposed’ until the date of surgery; after the date of surgery they are classified as exposeda. | ||
| Follow-up: Starts at date of diagnosis. Women are followed until death, loss to follow-up, or end of study period. | ||
| Time-varying exposure (yes/no surgery) (3, 4) with specified treatment window | Included: All women with metastatic cancer | Effect of undergoing resection within 8 months of diagnosis, compared to never or undergoing resection later, on mortality. |
| Treatment status: Surgical resection within a specified treatment window (e.g., 8 months after diagnosis). Women are classified as being ‘unexposed’ until the date of surgery; after the date of surgery they are classified as exposeda. Women who undergo resection after the treatment window are classified as unexposed. | ||
| Follow-up: Starts at date of diagnosis. Women are followed until death, loss to follow-up, or end of study period. | ||
| Landmark approach (6, 7) | Included: All women with metastatic cancer and who are alive and not lost to follow-up before landmark | Effect of undergoing resection within 8 months of diagnosis, compared to never or undergoing resection later, on mortality, among women who survive at least 8 months after diagnosis. |
| Treatment status: Women who undergo resection prior to the landmark are considered exposed, and individuals who do not are unexposed. | ||
| Follow-up: Starts at a landmark time-point (e.g., 8 months) following cancer diagnosis. Women are followed until death, loss to follow-up, or end of study period. | ||
| Clone-censor-weight method (8–10) | Included: All women with metastatic cancer are included twice; once in each treatment arm (surgical resection and no resection) | Effect of undergoing resection within 8 months of diagnosis, compared to never or undergoing resection later, on mortality. |
| Treatment status: Assigned. Treatment is defined to occur within a specified time frame (e.g., 8 months) | ||
| Follow-up: Starts at date of diagnosis. Patients are followed until their treatment is no longer compatible with the treatment assignment (e.g., “unexposed” women are censored at the time of resection and “exposed” women are censored at 8 months if they do not undergo resection), death, loss to follow-up, or end of study period. |
aWhile in our analyses we assumed a ‘once exposed, always exposed’ approach given that our treatment of interest was surgery, these methods allow for individuals to be switched from unexposed to exposed and vice versa across the entire study period; studies on medication adherence or other treatments may want to reclassify individuals as unexposed as treatment is discontinued; lag effects of treatments can also be incorporated.