Until recently, only one underlying cause of death on death certificates has been
routinely coded and analysed in most countries including England. By omitting causes
of death that are not coded as the underlying cause, official statistics underestimate
the extent to which specific diseases, such as specific cancers, contribute to the
mortality of a population.
Interpretation of mortality statistics based only on underlying cause is also complicated
by changes over time in the rules for selecting the underlying cause. Rules changed
in England in 1984 and 1993 with different approaches to applying rule 3 of the International
Classification of Diseases (ICD) (WHO, 1977; OPCS, 1985; Harvey et al, 1991; ONS,
1996). This rule specifies a number of diseases, including pneumonia, thromboembolism
and heart failure, that should not be coded as the underlying cause of death, even
if certified as such by the certifying doctor, if other diseases such as cancer are
also on the death certificate; instead, rule 3 prescribes that the other disease should
be selected as the underlying cause (WHO, 1977). The rule was rigorously implemented
by the Office of National Statistics in England and Wales in the period 1984–1993
and then partially reversed (OPCS, 1985; ONS, 1996). In 1993, multiple-cause coding
of death certificates was introduced as standard practice in England, but information
about multiple-cause mortality for longer-term trends is not available nationally.
We have used a regional database that included all certified causes of death from
1979 to 1999, not just those selected as the underlying cause, with the aim of comparing
underlying- and multiple-cause-coded rates for cancers.
METHODS
The former Oxford National Health Service Region covered a total population of about
2.5 million people. All causes of death on each death certificate in this population
were coded for the years 1979–1999, for the Oxford record linkage study (Goldacre
et al, 2000), using the 9th ICD revision codes. In each year, the underlying cause
of death was selected and coded according to the prevailing national rules. Following
convention, all certified causes of death – underlying cause plus causes elsewhere
on the certificate – are termed ‘mentions’.
The database was searched for records with mentions of malignant neoplasms (ICD codes
140–208). We analysed the data in three time periods defined by changes to coding
rules, 1979–1983, 1984–1992 and 1993–1999, to calculate the percentage of mentions
that were coded as the underlying cause of death in each period. We tested changes
in these percentages between time periods by χ
2 tests on the numbers on which the percentages were based. We then calculated changes
over time in annual mortality rates, standardised by applying the age-specific rates
in the Oxford region population in each year to the European standard population.
We calculated the average annual percentage change over time in mortality rates for
mentions by fitting linear regression models to the logarithms of the death rates.
We calculated changes in rates for mentions using every individual year. We calculated
rates for underlying cause using individual years before and after the rule 3 changes,
that is, omitting data for 1984–1992. We omitted these years to determine whether,
if the discontinuity in the application of the rule was ignored, trends in mentions
and underlying cause were similar.
RESULTS
Table 1
Table 1
Mention-based mortality rates per 100 000 population; ratio of death with a mention
of each cancer to death certificates with the cancer as the underlying cause of death;
and average annual change in mortality rates with 95% confidence interval (95% CI
in italics)
Ratio of mentions to underlying cause
Cancer site or type (ICD codes; N=number of deaths with mentions)
Mention-based mortality rates per 100 000 1979–1999
1979–1983
1984–1992
1993–1999
Average annual % change in mortality rates and 95% CI: mentions, 1979–1999
Average annual % change in mortality rates and 95% CI: underlying cause 1979–1999
excluding 1984–1992
All cancer (140–208; N=128 068)
228.7
1.11
1.07***
1.10***
−0.8
−0.9
−0.6
−0.7
−0.9
−0.6
Tongue (141; N=365)
0.7
1.24
1.17
1.20
−0.1
−2.1
1.9
0.1
−1.9
2.2
Salivary glands (142; N=176)
0.3
1.07
1.08
1.19
−0.2
−2.9
2.5
−1.6
−4.2
1.2
Nasopharynx (147; N=127)
0.2
1.07
1.10
1.19
−3.3
−5.7
−0.8
−4.0
−7.3
−0.5
Oesophagus (150; N=4499)
7.9
1.09
1.05***
1.06
1.6
0.9
2.2
1.7
0.9
2.6
Stomach (151; N=6858)
12.4
1.08
1.06***
1.07*
−4.2
−4.6
−3.7
−4.1
−4.5
−3.7
Rectum (154; N=5318)
9.5
1.14
1.12
1.14*
−2.3
−2.8
−1.7
−2.4
−2.9
−1.9
Colon and rectum (153−154; N=15 572)
27.0
1.15
1.10***
1.13***
−1.4
−1.8
−1.1
−1.4
−1.7
−1.0
Liver and intrahepatic bile ducts (155; N=1256)
2.2
1.23
1.05***
1.07
2.5
2.0
3.0
3.5
2.8
4.2
Gallbladder and extrahepatic bile duct (156; N=729)
1.2
1.09
1.05
1.10
−4.5
−5.7
−3.3
−4.6
−5.9
−3.3
Pancreas (157; N=5375)
9.3
1.07
1.03***
1.04
−0.5
−0.9
−0.2
−0.4
−0.8
0.1
Digestive organs and peritoneum (159; N=997)
1.5
1.09
1.06
1.13**
8.1
6.7
9.6
7.9
6.3
9.6
Nasal cavities, middle ear, access sinuses (160; N=161)
0.3
1.19
1.05
1.09
−5.6
−8.6
−2.4
−4.8
−8.6
−0.8
Larynx (161; N=775)
1.5
1.22
1.28
1.44*
−0.6
−2.0
0.9
−1.7
−3.5
0.2
Trachea, bronchus and lung (162; N=28021)
53.3
1.06
1.05
1.06***
−2.3
−2.6
−2.1
−2.4
−2.6
−2.1
Pleura (163; N=373)
0.7
1.06
1.04
1.02
4.8
3.0
6.6
5.0
3.4
6.7
Bone and articular cartilage (170; N=282)
0.5
1.16
1.08
1.05
−1.2
−3.8
1.5
0.0
−2.5
2.6
Connective and other soft tissue (171; N=563)
1.0
1.12
1.06
1.09
1.7
0.2
3.2
1.9
0.3
3.5
Malignant melanoma of skin (172; N=1268)
2.3
1.09
1.07
1.06
2.3
1.2
3.4
2.7
1.1
4.3
Other cancer of skin (173; N=463)
0.8
1.62
1.39
1.56
−0.6
−2.3
1.1
0.0
−1.7
1.8
Female breast (174; N=13807)
44.3
1.14
1.10***
1.15***
−0.8
−1.2
−0.5
−0.9
−1.3
−0.4
Uterus, part unspecified (179; N=650)
1.9
1.30
1.13**
1.22*
−1.3
−3.5
1.0
−0.7
−3.2
1.8
Cervix (180; N=1367)
4.7
1.11
1.09
1.15*
−4.1
−5.2
−3.0
−4.2
−5.5
−3.0
Body of uterus (182; N=789)
2.4
1.15
1.16
1.20
−2.7
−3.9
−1.4
−3.2
−4.5
−1.9
Ovary and other uterine adnexa (183; N=3503)
12.0
1.05
1.03
1.06***
0.3
−0.5
1.0
0.2
−0.5
0.9
Prostate (185; N=8732)
35.0
1.39
1.19***
1.30***
1.5
1.2
1.9
1.9
1.2
2.6
Testis (186; N=134)
0.5
1.03
1.15
1.72**
−3.6
−7.0
0.0
−6.5
−9.2
−3.7
Penis (187; N=125)
0.5
1.39
1.06**
1.28*
−3.9
−6.6
−1.0
−3.4
−6.2
−0.7
Bladder (188; N=4759)
8.7
1.30
1.21**
1.26**
1.0
−1.4
−0.6
−0.9
−1.3
−0.5
Kidney (189; N=2338)
4.3
1.18
1.11**
1.15
1.8
0.9
2.6
1.8
1.0
2.5
Brain (191; N=2541)
4.9
1.04
1.02*
1.04*
0.5
−0.2
1.2
0.3
−0.3
0.9
Thyroid gland (193; N=299)
0.5
1.13
1.10
1.15
−1.3
−3.5
1.0
−2.1
−3.7
−0.5
Lymphosarcoma, reticulosarcoma (200; N=282)
0.5
1.12
1.20
1.19
−10.0
−12.0
−8.0
−10.1
−12.5
−7.5
Non-Hodgkin's lymphoma (200+202; N=3642)
6.4
1.19
1.12**
1.18***
1.7
1.1
2.2
1.6
1.1
2.1
Hodkin's disease (201; N=489)
0.9
1.20
1.20
1.40*
−4.2
−6.0
−2.4
−5.1
−6.9
−3.3
Other cancer of lymphoid and histiocystic tissue (202; N=3364)
5.9
1.21
1.11***
1.18***
2.9
2.3
3.5
3.0
2.2
3.7
Multiple myeloma and immunoproliferative cancers (203; N=2292)
4.0
1.20
1.12**
1.20***
0.4
−0.3
1.0
0.2
−0.7
1.2
Lymphoid leukaemia (204; N=1447)
2.5
1.39
1.39
1.56*
−0.6
−1.9
0.8
−1.5
−3.4
0.4
All cancers with more than 400 cases, or with significant changes in ratios or annual
rates (cancers coded as those at ill-defined or unspecified sites excluded)
*
P<0.05;
**
P<0.01;
***
P<0.001.
shows the extent to which underlying cause statistics underestimate the total mortality
ascribed to cancers. For example, in 1993–1999 mortality from all cancer was 10% higher,
and that from breast cancer was 21% higher, than that judged from data on underlying
cause alone.
Comparing periods with different coding rules (Table 1), the ratio of mentions to
underlying cause showed statistically significant and noteworthy differences for cancer
of the colon, liver, breast, prostate, testis, bladder, Hodgkin's disease, non-Hodgkin's
lymphoma, lymphoid and myeloid leukaemia (we defined noteworthy as a significant change
in the ratio of more than 5%). Statistically significant, but numerically smaller,
changes in the ratios between the periods with different coding rules were seen for
cancers of the oesophagus, pancreas and lung. Changes in the ratios coinciding with
rule changes can be interpreted using prostate cancer as an example: between 1979–1983
and 1984–1992, the ratio of mentions to underlying cause decreased from 1.39 to 1.19,
or, in other words, in the later of the two periods a higher percentage of certificates
that included prostate cancer were coded with prostate cancer as the underlying cause.
This meant that underlying-cause mortality rates for prostate cancer (the only rates
available from routine statistics) exaggerated the rise from 1979–1983 to 1984–1992.
The subsequent increase in the ratio of mentions to underlying cause, from 1.19 in
1984–1992 to 1.30 in 1993–1999, means that a lower percentage of cases with prostate
cancer were coded with the disease as the underlying cause in the later than in the
earlier of these two periods. In this example, the trends for underlying-cause and
mentions converge comparing the first and second periods, and diverge comparing the
second and third periods (Figure 1
Figure 1
Mortality rates for cancer of prostate, expressed as age-standardised rates per million
population and as 3-year moving averages around each calendar year, comparing prostate
cancer coded as the underlying cause of death, and coded as a cause on any part of
the death certificate.
).
Age-standardised death rates, expressed as mentions per 100 000 resident population,
showed a significant increase over time for cancers of the oesophagus (in men only),
liver, malignant melanoma, prostate, kidney, and non-Hodgkin's lymphoma. Significant
decreases over time were found for cancers of the lip, stomach, colon, rectum, gall
bladder, pancreas, lung (in men only), breast, bladder, Hodgkin's disease and non-Hodgkin's
lymphoma. Omitting the middle time period, these trends based on underlying cause
were similar to those based on mentions.
DISCUSSION
The ratios of mentions to underlying cause show the extent to which statistics for
underlying cause, alone, have underestimated the population toll of cancer mortality.
For certain cancers, studies of trends in rates that use underlying cause only, starting
or finishing in years between 1984 and 1992, may be misleading. In general, however,
the impact of the rate changes on cancer was small. Particularly, if data for the
years 1984–1992 are ignored, rates show similar trends whether analysed for mentions
or for underlying cause. As we have shown, even over a period as short as two decades,
many cancers show significant upward or downward trends.
Consideration needs to be given to the distinction between dying with a cancer and
dying from a cancer. Particularly for cancers in which therapy has been successful,
the certifying doctor may consider that the cancer, though appropriate to certify
as a contributing cause, was not the underlying cause of death. As treatment improves,
for some cancers it can be expected that there will be a trend away from certifying
the cancer as the underlying cause of death in affected people who die. Testicular
cancer and Hodgkin's lymphoma are examples (Table 1). Trends in mortality statistics
for cancer, based on underlying cause alone, may be particularly difficult to interpret
when the period studied coincides with changes in practice in the selection of the
underlying cause.
CONCLUSION
Multiple-cause coding of mortality in England has become routine since 1993. In analysing
cancer mortality rates, consideration should be given to rates based on mentions as
well as underlying cause, particularly when the analysis crosses periods of change
to selection rules.