An application using Chennai PBCR data

Table 15: Number of cases variably classified as alive or dead under different assumptions of follow up by cancer site, Chennai PBCR, 1990-1999 (II)

Number of cases by vital status included for analysis Passive follow up only Passive + active follow up

Case 1 Case 2 Case 3 Case 4

Cancer/Site Total Dead

Presumed alive at closing date

Dead

Presumed alive at closing date

Dead Alive LFU Dead Alive

Lip 86 17 69 46 40 46 10 30 46 10

Tongue 988 371 617 693 295 693 54 241 693 54

Oral cavity 1662 528 1134 1052 610 1052 169 441 1052 169

Tonsil 250 107 143 214 36 214 16 20 214 16

Hypopharynx 1017 421 596 833 184 833 59 125 833 59

Oesophagus 2016 1028 988 1759 257 1759 59 198 1759 59

Stomach 2681 1392 1289 2277 404 2277 120 284 2277 120

Pancreas 328 190 138 291 37 291 23 14 291 23

Larynx 722 290 432 456 266 456 142 124 456 142

Lung 1806 1069 737 1574 232 1574 45 187 1574 45

Breast 3067 875 2192 1489 1578 1489 862 716 1489 862

Cervix 4438 1131 3307 1874 2564 1874 878 1686 1874 878

Ovary 808 321 487 487 321 487 138 183 487 138

Urinary bladder 442 172 270 305 137 305 62 75 305 62

Hodgkin lymphoma 298 92 206 171 127 171 74 53 171 74

Non Hodgkin lymphoma 868 383 485 602 266 602 130 136 602 130

Lymphoid Leukaemia 433 197 236 323 110 323 49 61 323 49

Myeloid Leukaemia 465 277 188 365 100 365 35 65 365 35

Leukaemia unspecified 85 56 29 69 16 69 5 11 69 5

PBCR: Population Based Cancer Registry; LFU: Lost to Follow Up

Case 1: Passive follow up only without any active follow up with cancer cases not matched with official mortality database presumed to be alive on the closing date of follow up.

Case 2: Passive + Active follow up with lost to follow up cases presumed alive on the closing date.

Case 3: Passive + Active follow up with lost to follow up cases censored at the last known date.

Case 4: Passive + Active follow up with lost to follow up cases excluded from survival analysis.

Table 15 gives the distribution of cases of major cancers by vital status, variably classified as alive or dead, based on different assumptions made on each case following the method adopted for getting the outcome data on follow up (II). In the example of cervix cancer, there were a total of 4,438 cases included for survival analysis. Of these, in reality, there were 1,131 (25.5%) deaths matched from the official mortality data from vital statistics division, 743 (16.7%) cases were known to be dead by active follow up methods (by actions AE or AP as in Table 2 in section 4.3.1) yielding a total of 1874 (42.2%) deaths; 878 (19.8%) cases were known to be alive on the closing date of follow up on December 31, 2001; for the rest of 1686 (38.0%) cases, alive or dead status was not known on this date as they had been lost to follow up at variable times between 1990 and 2001. The vital status of cases gets transformed when different assumptions are made.

If we assume that only passive follow up was adopted and no active follow up was pursued in Chennai, then we know death information on 1131 cases only, instead of 1874 deaths in reality. By rule, under passive follow up environment, if death information is not forthcoming, such cases are presumed to be alive. So, 743 deaths obtained by active methods of follow up plus 878 cases actually alive on closing date plus 1686 cases whose vital status was actually unknown at closing date will all be erroneously assumed to be alive on closing date (Case 1-purely passive method of follow up).

Suppose we assume that there is a moderately developed health information system functioning locally which can correctly identify all deaths occurring in the region and minimal active follow up with impersonal approach is adopted for follow up (by actions AP

as in Table 2 in section 4.3.1), then at the most, 1874 deaths will be known. By rule, under passive follow up environment, 878 cases actually alive on closing date plus 1686 cases that

were actually lost to follow up at variable intervals between 1990 and 2001 would all be assumed to be alive on the closing date (Case 2-predominantly passive method of follow up).

Suppose we assume the situation as it exists, then there would be 1874 deaths of cervix cancer cases, 878 cases alive on closing date and 1686 cases lost to follow up before closing date (Case 3-active method of follow up). Suppose we decide to exclude the cases, on whom, the alive or dead status was not known on closing date, then the analysis will include only 2752 cases: 1874 deaths and 878 alive cases, instead of 4438 (Case 4-predominantly active method of follow up).

There is variable impact caused by above scenarios on different cancers based on the availability of mortality data and extent or magnitude of losses to follow up. It is evident that the absolute survival estimated under different assumptions as stated above will also be different for different cancers. It becomes important to elucidate the bias arising out of such different misclassification of vital status (alive or dead) of cases in the analysis for major cancers.

Table 16: 5-year absolute actuarial survival% estimated under different assumptions on the vital status by method of follow up, Chennai PBCR 1990-1999 cases followed through 2001 (II)

Methods of follow up and different vital status assumptions Passive follow up Passive + Active follow up

All cases not

The five year absolute survival estimated by actuarial methods under different assumptions on the vital status of the cases based on corresponding assumption on the follow up environment or methods of follow up as totally passive or active or a mixture of both using Chennai population-based cancer registry data during 1990-1999 are given in Table 16 (II). The survival estimated by following case 1 was the highest and by following case 4 was the lowest for all cancers. Case 3, which treats vital status of subjects as is, is taken as standard. The absolute difference in estimated survival by case 1, case 2 and case 4, compared to case 3 represents the bias. In the absence of active follow up (case 1), 5-year absolute survival was estimated to be higher by 22% (in leukaemia unspecified) to 47% (in hypopharyngeal cancer) than when cases were actively followed and were lost to follow up at a known point in time (case 3). The bias ranged between 3 (for pancreas) and 10 (for tongue) percent units for case 2 vs. case 3. When follow up methods were totally by active methods but losses to follow up cases were excluded from analysis, the bias induced varied between 2-8 percent units for different cancers. The more losses to follow up the greater are the uncertainty and potential for bias, in the actuarial estimate. Cases 2 and 4 represent the two extremes of a survival spectrum, with the actuarial estimate assuming random withdrawal (case 3) falling in between. The absolute differences in 5-year survival between cases 2 and 4 were substantial for cancers of the tongue (13.8%) and ovary (18.4%).