Conflicts of interest and pandemic flu
BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c2947 (Published 04 June 2010) Cite this as: BMJ 2010;340:c2947
All rapid responses
We have to agree with the Editor in Chief when she states:
“The big question is what to do about the conflicts.
On the basis of our own investigation and those of others, the answer is
now inescapable. As Barbara Mintzes says in Cohen and Carter’s report, "No
one should be on a committee developing guidelines if they have links to
companies that either produce a product—vaccine or drug—or a medical
device or test for a disease." The same, and more, must apply to
committees making major decisions on public health.
Where entirely independent experts are hard to find, experts who are
involved with industry could be consulted but should be excluded from
decision making.”
(BMJ 2010;340:c2947 Fiona Godlee, editor in chief)
Has the BMJ editorial board considered the possibility of having
commercial conflict of interest statements include the amounts of
remuneration that someone has been paid historically for acting on behalf
of a third party with a vested interest, and how much they will receive
for work under consideration?
Furthermore, given the BMJ’s concern about commercial conflict of
interest would it not make sense to move towards excluding those
conflicted relations from the peer review process as well? Where
independent experts can not be found, it could be stated explicitly in the
review process and with publication. Moving towards a review system that
excludes peer-reviewers with commercial vested interests is a logical
extension of the position that Godlee advocates in her editorial and would
better serve the public health.
Competing interests:
None declared
Competing interests: No competing interests
I've just been made aware that the figure of $7bn for industry
profits from the sale of influenza vaccines, quoted in this editorial and
referenced to the Council of Europe report, is likely to be wrong. As soon
as I have a more accurate figure I will publish a correction.
Competing interests:
None declared
Competing interests: No competing interests
I was interested to note the words taken by Fiona Godlee from the
Cohen and Carter report: "No one should be on a committee developing
guidelines if they have links to companies that either produce a
product—vaccine or drug—or a medical device or test for a disease."(1). A
topic of much debate recently has been NICE's thromboembolism
guidelines(2). Those with conflicts of interest on the NICE panel include
Nandam Gautam (Bristol Myers-Squibb), Aroon Hingorani (Pfizer), Beverley
Hunt (Sanofi Aventis, Bayer and Boehringer), Nigel Langford (Sanofi
Aventis), Simon Noble (Leo Pharma, Boerhinger Ingelheim, Sanofi Aventis),
Annie Young (GlaxoSmithKline), Simon Frostick (Boehringer Ingelheim,
Bayer), David Warwick (Boerhinger Ingelheim, Sanofi Aventis) and Nick
Welch (Boerhinger Ingelheim). Cosequently I wonder if these guidelines
are worth the paper they are written on?
1. Godlee F. Conflicts of interest and pandemic flu. BMJ
2010;340:c2947
2. Venous thromboembolism: reducing the risk of venous
thromboembolism (deep vein thrombosis and pulmonary embolism)in patients
admitted to hospital. NICE. January 2010.
Competing interests:
None declared
Competing interests: No competing interests
The work carried out by the BMJ is very important for the
understanding of what led to the declaration of the A H1N1 pandemic and
how it has been handled. Another issue of interest in this context is how
the original outbreak was managed by the Mexican health authorities that
sparked the declaration of the pandemic.
The analysis of the official data show that there was an initial
denial of the outbreak, followed by the declaration of an emergency that
rapidly turned into a virtual paralysis of the economy and social life
that was later tuned down despite the fact that the highest numbers of
deaths and illness occurred five months later.
The analysis of data on Influenza registered by the epidemiological
surveillance system (www.dgepi.salud.gob.mx/boletin/boletin.htm) shows
that the epidemic started in February but was not recognized until late
April. Furthermore comparative data from uniform epidemiological area
split into different administrative unities are very inconsistent. For
instance, for each case registered in the municipalities surrounding the
Federal District there were eight cases registered in the Federal
District. This situation should have led to a close revision of data that
however was taken at face value. Furthermore the discrepancies in
mortality rate reported for Influenza AH1N1 was 0.35 per 100,000 in the
Federal District and 0.16 in the surrounding municipalities.
It also becomes clear that the field studies of cases-contacts, a
compulsory task of local health authorities, were not done or were not
reported. Apparently the estimates of attack rate and case fatality rates
were not calculated which would have shown that the new virus was quite
mild; information that would have been highly relevant for decision
making.
The analysis of cases and deaths by age group using reported data for
2009 reveals some interesting traits (
www.salud.gob.mx/demograficos/poblacion.html and
http://portal.salud.gob.mx/contenidos/noticias/influenza/estadisticas.html).
The general fatality rate is 1.3 per 100 confirmed cases and by age groups
as follows: 50-59 years with 4.95 followed by 60 years or older with 3.9,
40-49 with 3.3 and 30-39 with 2.61. The mortality rates per 100,000 are
slightly different but the highest is registered for the age group 50-59
(1.83) followed by 40-49 (1.3) and 30-39 (1.18) which does not coincide
with the suggestion that young adults have the highest risk. Finally the
incidence, a proxy to attack rate, is low 0.01 to 0.09 per 100 and has a
clear age gradient.
An early and comprehensive analysis of Mexican data and the basic field
studies would have provided a wealth of information to the WHO in its
evaluation of what measures to take in relation to Swine Flue and the
pandemic alert. This was not done and the economic cost to Mexico has been
very high as well as to the rest of the world. Why this was disregarded
could be interpreted in different manners. One reasons could be that the
Mexican health reform has disrupted primary health care that integrated
public health interventions and assistance to the sick. If cases are not
detected, reported and followed up with routine public health actions the
result is that the sick do not get care and communities are not protected.
The artificial separation between public and private “goods” ends up
sacrificing persons and communities. Another hypothesis is that power
groups played an important role not to produce evidence contrary their
vested interest.
The full text of this analysis is found at:
http://www.elagora.org.ar/site/posibles/inicio-Posibles.html
Correspondence to laurell9998@gmail.com
Dr. Asa Cristina Laurell,
Former Secretary of Health in Mexico City.
Competing interests:
None declared
Competing interests: No competing interests
Sir
I commend on the investigative approach of your journal.
At the start of the "swine flu pandemic" in Hong Kong, which
responded by keeping tourists under quarantine in a hotel, I was asked by
reporters about the future of this threat. I reassured them that this was
a false alarm, and that it was nothing like SARS, which gave Hong Kong a
harsh lesson in 2003 (and for which I criticized the public health
officials harshly for their slow action). My complacent response was based
on two observations: First, mortality rate was not high. (There were a
number of deceased where the virus was isolated, but that did not mean
they died of H1N1 influenza.) Secondly, infectivity was not high. I found
it hard to justify the WHO raising the alarm to pandemic level. However, I
told the reporters that the health officials will respond exactly
according to what WHO recommended. This was a case I called the butt
commanding the brain (a Cantonese saying which means one's decision
depends on the post one is holding, not on rational thinking). If I were
the health secretary or director, I would have nothing to gain if I insist
on my own judgement, even though it was based on sound epidemiological
evidence. On the contrary, if I did insist on my own view, and the
epidemic worsened, my head would roll. After all, who could criticize me
if I, like health officials all over the world, faithfully did what WHO
recommended?
So, Hong Kong responded by spending millions on vaccination
and stockpiling of oseltamivir. (The latter recommendation, advocated as a
preventive measure against the highly lethal avian flu, was especially
open to questioning, since most cases of avian flu did not respond to the
drug.) The vaccination programme ended with a few cases of Guillain Barre
syndrome that no one could rule out the vaccine as a cause. The result -
about 90% of the vaccines were not used. Even for relatively affluent Hong
Kong, the opportunity cost is substantial. Yet, the health authority said
this was insurance premium worthy of paying. No lesson was learnt.
TW Wong
School of Public Health and Primary Care
The Chinese University of Hong Kong
Competing interests:
None declared
Competing interests: No competing interests
Sir:
It was unfortunate that mass vaccination was the only method chosen to
combat the A(H1N1) influenza outbreak by the WHO. There is mounting
evidence that vitamin D can reduce the risk of both seasonal and pandemic
type A influenza and its complications such as pneumonia. The link was
hypothesized by John J. Cannell and coworkers in 2006 [Cannell et al.,
2006] and quickly supported by the results of a randomized controlled
trial [Aloia and Li-Ng, 2007; Cannell et al., 2008]. Stronger support was
provided recently based on results of a randomized controlled trial of
1200 IU/day of vitamin D3 vs. 200 IU/day involving Japanese school
children [Urashima et al., 2010]. An ecological study of the 1918-19
A(H1N1) influenza in the United States found that living in more southern
states greatly reduced the case-fatality rate, due primarily from
pneumonia about 10 days after developing influenza [Grant and Giovannucci,
2009]. The effects of vitamin D in fighting infections are well known
[Dogan et al., 2009; White et al., 2009]. The mechanisms for reducing the
risk of pneumonia included reducing the cytokine storm and fighting the
bacterial infection [White, 2009].
The overall benefits of vitamin extend to many types of cancer,
cardiovascular disease, diabetes, autoimmune diseases, etc. [Holick,
2007]. Many of those who had complications from the A(H1N1) influenza
were groups known to have low serum 25-hydroxyvitamin D lelels: pregnant
women, Australian Aborigines, the obese, diabetics, and people with other
comorbidities.
Raising serum 25-hydroxyvitamin D levels to 100 nmol/L could reduce
the countrywide mortality rates by 15% and the economic burden of disease
by 10% [Grant et al., 2009]. Vitamin D is much less costly than
vaccinations and adverse side effects from as much as 5000 IU/day are
extremely rare.
It is hoped that the world's health policy leaders will take the time
to learn more about the health benefits of vitamin D and recommend that
people obtain more vitamin D from solar ultraviolet-B irradiance or
supplements as appropriate.
William B. Grant
wbgrant@infionline.net
References
Aloia JF, Li-Ng M. Re: epidemic influenza and vitamin D. Epidemiol Infect.
2007 Oct;135(7):1095-6; author reply 1097-8.
Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S,
Garland CF, Giovannucci E. Epidemic influenza and vitamin D. Epidemiol
Infect. 2006 Dec;134(6):1129-40.
Cannell JJ, Zasloff M, Garland CF, Scragg R, Giovannucci E. On the
epidemiology of influenza. Virol J. 2008 Feb 25;5:29.
Dogan M, Erol M, Cesur Y, Yuca SA, Doðan Z. The effect of 25-
hydroxyvitamin D3 on the immune system. J Pediatr Endocrinol Metab.
2009;22:929-35.
Grant WB, Giovannucci D. The possible roles of solar ultraviolet-B
radiation and vitamin D in reducing case-fatality rates from the 1918–1919
influenza pandemic in the United States. Dermato-Endocrinology 2009;1:215-
9.
Grant WB, Cross HS, Garland CF, Gorham ED, Moan J, Peterlik M,
Porojnicu AC, Reichrath J, Zittermann A. Estimated benefit of increased
vitamin D status in reducing the economic burden of disease in Western
Europe. Prog Biophys Mol Biol. 2009 Feb-Apr;99(2-3):104-13.
Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266
-81.
Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H.
Randomized trial of vitamin D supplementation to prevent seasonal
influenza A in schoolchildren. Am J Clin Nutr. 2010;91:1255-60.
White AN, Ng V, Spain CV, Johnson CC, Kinlin LM, Fisman DN. Let the
sun shine in: effects of ultraviolet radiation on invasive pneumococcal
disease risk in Philadelphia, Pennsylvania. BMC Infect Dis. 2009;9:196.
Competing interests:
I receive funding from the UV Foundation (McLean, VA), the Sunlight Research Forum (Veldhoven), Bio-Tech-Pharmacal (Fayetteville, AR), and the Vitamin D Council (San Luis Obispo, CA) and have received funding from the Vitamin D Society (Canada).
Competing interests: No competing interests
Re: Correction to figure on industry profits
In this editorial I quoted a figure of $7-10bn as the industry's
profit from the sale of pandemic flu vaccines. This figure is incorrect.
It was taken from a Council of Europe report,[1] which quoted incorrectly
from a report by investment bank JP Morgan. The actual figure in the JP
Morgan report [2] referred to estimated total sales (not profit) for
pandemic vaccine and adjuvant, and was $6.9bn. Industry's audited accounts
for 2009 give sales figures for pandemic vaccine in 2009 in the region of
$2.5bn. Industry analysts I have spoken to suggest that the total sales of
pandemic flu vaccines from late 2008 through to early 2010 is likely to be
double this at around $5bn. Again this figure is an estimate for sales
revenue not profit.
[1] Flynn P. Social, Health and Family Affairs Committee.
Parliamentary Assembly of the Council of Europe. The handling of the H1N1
pandemic: more transparency needed. 2010.
http://assembly.coe.int/CommitteeDocs/2010/20100329_MemorandumPandemie_E....
[2] JP Morgan Europe Equity Research 15 July 2009
Competing interests:
None declared
Competing interests: No competing interests