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Long term study shows no increase in mortality or cancer in UK nuclear weapon test veterans

BMJ 2003; 326 doi: https://doi.org/10.1136/bmj.326.7387.468/d (Published 01 March 2003) Cite this as: BMJ 2003;326:468

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Underascertainment of multiple myeloma challenges robustness of third NRPB study of nuclear veterans

Dear Sir,

Your report (Long term study shows no increase in mortality or cancer
in UK nuclear weapon test veterans – BMJ 2003:326:468 1 March) does not
refer to the fact that there were 11 additional ‘agreed’ cases of multiple
myeloma that were not reported in the third NRPB study together with
several more documented cases that have not been ‘agreed’. However the
NRPB researchers argue that to include these additional 25-30% of known
multiple myeloma cases would bias the study because they were not
ascertained by the data linkage method alone. These additional cases
are hardly “anecdotal reports.”

The NRPB ascertained 35 cases of multiple myeloma among the 21,357
nuclear test veterans included in their study utilising the data linkage
between the ONS and the SROs. They reported the same number of cases among
the 22,333 controls who were veterans of the armed services who had not
served at nuclear weapons test sites. Two thirds of these 35 cases among
the nuclear test veterans had also been ascertained by the present
researcher. At the time of the inter-comparison the NRPB indicated that it
was aware of 5 cases not detected by the ONS-SRO data linkage method but
which they accepted were confirmed cases of multiple myeloma among
confirmed test participants. Three of these cases were also ascertained by
the present researcher. The NRPB termed these 5 cases ‘independent
responders’ and declined to include them in what they term ‘the main
study’. The NRPB also accepted 6 further cases ascertained by the present
researcher as valid cases of multiple myeloma among confirmed
participants, but also refused to include them in the main study. There
were thus 10 ‘accepted’ cases that were not included in the main study
which is to say that 24% of the 45 confirmed cases were excluded because
they had not been ascertained by the data linkage method. At least half
these eleven cases had received pensions for their multiple myeloma from
the War Pensions Agency (now the Veterans Agency) which is an agency of
the Ministry of Defence which commissioned the studies from the NRPB.
Eight of these eleven cases were veterans of the RAF.

There were an additional three cases identified by the present
researcher which the NRPB acknowledged were confirmed but whose data had
not appeared in the cancer registries in due time for the study although
their diagnoses were made within the study’s time frame. While it is
accepted that the ONS data can ‘lag’ by five years (Quinn, Botting, Foote
and Read 2000) it seems inappropriate to exclude cases that all within
the time frame of the NRPB’s study, i.e. to use the lag as an ‘excuse’
for exclusion in itself – from both the ‘main study’ and the list of
‘independent responders’. All three of these cases had been active before
the War Pensions Agency throughout the time frame of the study. This meant
that 14 of the 49 known cases of multiple myeloma – or 28.5% - were not
included in the NRPB study.

Another two cases were of men who had also been active before the
WPA, two of them receiving pensions for multiple myeloma during the time
frame of the study. Despite this they had not been ascertained as nuclear
test veterans by the Service Records Office.

This brought the number of confirmed cases of multiple myeloma among
documented test participants who were not included in the third NRPB
study to 16 - which is to say that nearly a third of the 51 confirmed
cases are not included in the results of the third NRPB study. An
additional case was excluded from the study because the individual served
in the Merchant Navy at the tests and the NRPB stated that it could not
track Merchant Navy participants. Another was excluded because he was
considered a civilian, even though he had been seconded to the RAF during
his service at the tests as a meteorologist. Civilian members of the
Atomic Weapons Establishment and the Atomic Weapons Research Establishment
are included in the study.

At least 30% of the confirmed cases of multiple myeloma among
documented participants in the UK’s atmospheric atomic and nuclear weapons
tests have been ascertained among the 15% of participants not included in
the NRPB studies. Those studies are therefore unrepresentative since the
rate of incidence and mortality from multiple myeloma - an accepted
radiogenic marker condition - is twice that of the main study among the
excluded cases.

The explanation for this bias lies largely in the fact that 11 of
these ‘independent responders’ - including 5 of the 6 cases accepted by
the NRPB from the present researcher and 3 of the independent responder
cases they were already aware of - served in the Royal Air Force at the
tests in what is acknowledged by the NRPB and the Ministry of Defence to
have been activities particularly vulnerable to radiation exposure. Air
crews flew threw mushroom clouds to collect fission samples; ground crews
worked on known contaminated planes. The NRPB’s second study estimated
that only 74% of eligible RAF participants had been included in the main
study’s cohort (NRPB, 1993, p.16). Of the 21,358 test participants
included in the second NRPB study, the largest group (39.5%) were from the
RAF (NRPB, 1993 p.4), yet the first NRPB study had estimated (NRPB, 1988
p.35) that the ascertainment rate for RAF participants in Operation
Grapple was only 70%. This weakness on the part of the Service Records
Office could have been remedied by a search of the claims files of the War
Pensions Agency/Veterans Agency.

The bias was compounded by the refusal of the NRPB to admit cases
where the lack of ascertainment was due to the lag in the ONS data, even
though the cases were shown to have been certified in death certificates
and diagnoses registered during the time frame of the third study. This
was despite being aware of Macdonald et al’s (1999) finding that direct
follow up identified 96% of cases and documented 11 cases not reported by
the UK’s NHSCR of ovarian cancer in a similar-sized cohort of 22,000
women. The NHSCR identified only 78% of the cases. Similarly, Dickinson
et al (2001) concluded that the NHSCR missed at least 10% of all incident
cases of malignant diseases. Dickinson et al conclude that “Without
additional ascertainment from multiple sources and diagnostic review, it
would be incautious to use NHSCR cancer registrations as the sole basis of
an epidemiological study.” Macdonald et al conclude that “some of these
limitations can be overcome by the use of an independent, direct method of
follow-up based on postal questionnaire.”

The NRPB contends that it cannot include these ‘independent
responders’ in the risk analysis calculations - even though they indicate
a major risk to the cohort of radiogenic multiple myeloma - because the
cases detected in the control group were ascertained by one strategy only
- the ONS/SRO linkage - and to ‘privilege’ the sample with multiple
ascertainment strategies creates its own bias. This is despite the fact
that the control group contains 976 more subjects than the sample, and
itself constitutes not 85% of a given cohort but simply a roughly
matching number of subjects.

In contrast, the Five Series studies (Thaul et al, 2000 p.19) of the
participants in the US nuclear weapons tests termed Operation Crossroads
used multiple ascertainment strategies to include 99% of cases in their
studies:
“The assembled information for this epidemiologic study comes from more
than 100 distinct sources. Handwritten paper logs, microfilm or
microfiche, computer files, medical records, word orders, transport
orders, memoirs, interoffice memoranda, testimony, secondary compilations
of primary sources, letters from spouses, death certificates, film badge
records, computer programs, and benefits and compensation claims represent
a diverse sample.” The Five Series study also relied on the Nuclear Test
Personnel Review database which included a nation-wide toll-free call-in
program set up the Defence Nuclear Agency (which became the Defence
Special Weapons Agency in 1996) for veterans of the US atmospheric tests
to report details of their participation. The Five Series researchers also
utilised the National Association of Atomic Veterans Medical Survey of
1784 veterans, advertised in a range of veterans’ journals and held public
meetings. Similar methods had been used earlier by Watanabe et al (1995)
in their study of cancer mortality risk among military participants of a
1958 US atmospheric nuclear weapons test.

The NRPB argues that it would bias the findings to include the cases
identified by strategies other than the simple data linkage that was used
for the control group. But as we have seen, the SROs were deficient in
their record-keeping particularly for the RAF subjects. It was known to
the NRPB researchers that a significant lag can occur in ONS
registrations. Since the incidence of multiple myeloma among the
independent responders is at least 30% - or twice the 15% rate estimated
by the NRPB in deciding to settle for an 85% sample cohort - the NRPB
studies seriously under-report the incidence of this marker radiogenic
condition among veterans of the UK’s atmospheric atomic and nuclear
weapons tests.

Yours sincerely,

Sue Rabbitt Roff

Cookson Senior Research Fellow

Dundee University Medical School,
484 Perth Road, Dundee DD2 1LR


email: s.l.roff@dundee.ac.uk

References

Darby SC et al (1988) Mortality and Cancer Incidence in UK
Participants in UK Atmospheric Nuclear Weapons Tests and Experimental
Programmes National Radiological Protection Board NRPB-R214 Chilton,
Didcot

Darby SC et al (1993) Mortality and Cancer Incidence 1952-1990 in UK
Participants in the UK Atmospheric Nuclear Weapons Tests and Experimental
Programmes National Radiological Protection Board NRPB-R266 Chilton,
Didcot

Dickinson HO et al (2001)How complete and accurate are cancer
registrations notified by the National Health Service Central Register for
England and Wales? J Epidemiol Community Health 55(6) 414-22

MacDonald N et al (1999) A comparison of national cancer registry
and direct follow-up in the ascertainment of ovarian cancer Br J Cancer
80(11), 1826-1827

MacDonald, Nicola, Menon, Usha and Jacobs, Ian (2000) Letter to the
Editor, Br J Cancer 82(2)279

Muirhead CR, Bingham D, Haylock RGE, O’Hagan JA, Goodill AA, Berridge
GLC, English MA, Hunter N, Kendall GM (2003a) Follow up of mortality and
incidence of cancer 1952-98 in men from the UK who participated in the
UK’s atmospheric nuclear weapons tests and experimental programmes.
Occupational and Environmental Medicine 60: 165-172

Muirhead CR, Bingham D, Haylock RGE, O’Hagan JA, Goodill AA, Berridge
GLC, English MA, Hunter N, Kendall GM (2003b) Mortality and Cancer
Incidence 1952-1998 in UK Participants in the UK Atmospheric Nuclear
Weapons Tests and Experimental Programmes National Radiological Protection
Board Didcot Oxfordshire NRPB-W27

Quinn MJ, Botting B, Foote D and Read (2000) A Registration of
ovarian cancer in England and Wales. Letter to the Editor. Br J Cancer
83(2), 278-9

Roff SR (1999) Incidence of Hemapoietic Cancers in a Sample of
Veterans of UK Nuclear Weapons Test, paper presented to First
International Conference on Multiple Myeloma and Amyloidosis, Manchester

Thaul S et al (2000) The Five Series Study Mortality of Military
Participants in U.S. Nuclear Weapons Tests. Washington DC National
Academy Press

Watanabe K et al (1995) Cancer Mortality Risk Among Military
Participants of a 1958 Atmospheric Nuclear Weapons Test American Journal
of Public Health 85 (4) 523-527

Competing interests:  
The research reported in this response was funded by a grant from the late Dame Catherine Cookson raised by the British Nuclear Tests Veterans Association.

Competing interests: No competing interests

07 March 2003
Sue R Roff
Cookson Senior Research Fellow
Dundee University Medical School 484 Perth Road, Dundee DD2 1LR