I agree we do have enough to say that we do not have enough evidence for a lot of aspects
Gloves, masks, and antiseptic wipes in primary care
Antivirals on different popultaions and different outcomes
Vaccination - combinations, sequences, outcomes, and subgroups
As Ian Chalmers says every intervention should be part of an RCT
This is what we should be asking for. There is a flu epidemic almost all the time somewhere in the world so it is just getting organised. Maybe Gates & Branson could help?
I think an editorial should be stating clearly the knowledge gaps and promoting the implementation of RCT's to fill those gaps
I am happy to start with the antivirals and mortality...is anyone else interested in this approach for publication or does anyone have other suggestions for getting this out into a wider domain.
Martin
I don't want to let people feel they have nothing though. What we should be
Maybe the best way is an editorial in the BMJ??
On 25/09/2009 21:44, "Puliyel" <[log in to unmask]> wrote:
Ben you write
These two threads deserve a full intellectual might of this wonderful discussion group. Perhaps, someone will notice?
There is no point in moaning about the ineffectiveness of EBM (in directing public health policy) between ourselves. It is likely no one will notice. And we cannot blame them because we have not put it to them.
We have enough evidence here.
Can we put it all together and write to the DG WHO and copy to world leaders (including leaders in developing countries who take pronouncements of the WHO very seriously). I am sure that will have some impact!
Jacob
On Sat, Sep 26, 2009 at 12:22 AM, Djulbegovic, Benjamin <[log in to unmask]> wrote:
Martin, this and paralell thread related to some unpublished data about interactions between seasonal and swine flu vaccine, is why the discussion groups like ours should exist. We have everything here:
- experts vs. evidence (it looks like that content i.e. "experts" always win)
- politics vs. EBM ( Tom: please send the article, which you forward to me, to the entire group. A fascinating piece!)
- (lack of evidence) vs. decision-making (it looks like that not acting is regretted more than acting even when uncertainty looms large?)
- if EBM is ignored in face of such multi-billion dollar decisions (which is what flu vaccine and antiviral will end-up costing) , the discussion about expensive but still benefical cancer drugs is too much about nothing, I am afraid (think about the opportunity costs here!)
These two threads deserve a full intellectual might of this wonderful discussion group. Perhaps, someone will notice?
thanks
ben
________________________________________
From: Evidence based health (EBH) [[log in to unmask]] On Behalf Of Martin Dawes, Dr. [[log in to unmask]]
Sent: Friday, September 25, 2009 10:31 AM
To: [log in to unmask]
Subject: Do the antivirals reduce mortality in flu? Roche thinks so on the basis of two retrospective studies
Last night I was at a pandemic planning meeting for GP's in Montreal where we were told by a local infectious disease expert that Tamiflu reduced mortality and we should give it to all at risk people with ILI and give it early.
When I asked for the data I was told that it was a new study from Dr Iacuzio (medical director of Roche: conflict of interest? - it only caused a small rise in share price - from 165 to 170 14th sept to 21st and it has slipped down again to 166)
The announcement was at 49th ICAAC
So 30 family doctors now think Tamiflu reduces mortality because of this non randomised data. The fact that one of the studies was in hospitalized patients and the advice was being given to community doctors makes this even more deceitful
Evidence based is not even part of medicine today and unlikely to be so in the face of such overwhelming ignorance.
Martin
Studies report higher survival rates in Tamiflu-treated patients
Singapore, Sep 14, 2009: Roche announced that two new observational studies concluded that influenza patients treated with Tamiflu (oseltamivir phosphate) had significantly higher survival rates than untreated patients. The studies, examining nearly 1,000 people, analyzed outcomes for two different groups -adults and children diagnosed with the highly pathogenic A (H5N1) avian influenza and adults hospitalized with seasonal influenza. Results, which build on similar findings, were presented at the 49th ICAAC annual meeting in San Francisco.
"These retrospective studies support the potential benefits of antiviral treatment in severe cases of influenza," said Dr Dominick Iacuzio, medical director at Roche, which manufactures Tamiflu. "While Tamiflu is approved and used in many countries to treat and prevent all types of A and B influenza, these 'real-world' studies contribute to the body of clinical evidence."
The first study examined outcomes data for 215 patients from 10 countries who were diagnosed with the virulent A (H5N1) avian influenza. The retrospective observational study found that untreated patients had a mortality rate of 88%, with 11 out of 89 (12%) untreated patients surviving, in contrast to survival of 45 out of 85 (53%) patients who received at least one dose of Tamiflu up to eight days after symptom onset. Among a subset of patients who received Tamiflu within two days of symptom onset, 5 out of 7 patients (71%) survived.
The study was conducted by researchers from Avex Avian Influenza Expert Group and the London School of Hygiene and Tropical Medicine, in collaboration with Roche. It is the first to systematically assess human A (H5N1) infection in multinational cases. Data were collected in-country and supplemented with data abstracted from published cases. Data were anonymized and reviewed for accuracy. Nearly all cases were confirmed at laboratories accredited by the World Health Organization (WHO).
"These data confirm the importance of prompt diagnosis and treatment with Tamiflu. They also support previous studies indicating that treatment may still beneficial even after 48 hours," explained Dr. Iacuzio.
The A (H5N1) avian influenza virus continues to spread throughout parts of Southeast Asia, Africa and the Middle East. Since 2003, the WHO has reported 440 human cases of A (H5N1), 262 of them fatal.
The second study analyzed 760 patients hospitalized with severe seasonal influenza, half of whom received Tamiflu (n=395). The data showed that the rate of mortality was reduced by 37% in patients treated with Tamiflu compared to patients who were not treated [3.8% in patients treated with Tamiflu compared to 6.0% in patients who did not receive treatment, adjusted Hazard Ratio 0.38(0.19,0.78)].
The retrospective, observational study was conducted in two general hospitals in Hong Kong during a 24-month period, studying patients over the age of 18 who were hospitalized with confirmed influenza. Most patients were older (average age 70), 60% had underlying chronic illness, and 78% were hospitalized with influenza complications.
http://www.biospectrumasia.com/content/140909OTH10638.asp
On 2009-09-25, at 9:50 AM, Dr. Carlos Cuello wrote:
http://link.reuters.com/cad68d
WHO is making recommendations based on experience from observational data and indirect from seasonal flu and in vitro tests (virus resistance)
Somehow, the recommendations still aré strong. I guess, for physicians wanting to based their clinical decisions on evidence, these aré the most difficult topics, when the evidence is low quality but recommendations are strong.
BTW is someone running a RCT about Tamiflu on H1N1?
It ' d be interesting to check clinicaltrials.gov <http://clinicaltrials.gov> <http://clinicaltrials.gov/> & others
Enviado desde mi iPhone
El 25/09/2009, a las 03:47, Richard Nicholl <[log in to unmask]<mailto:[log in to unmask]>> escribió:
"People take Tamiflu, Doctors prescribe Tamiflu (not because they expect any noticeable benefit but because they fear what might happen if they don't) and they get better, and the epidemic subsides; and everybody has been a good citizen and so thus proves that the Tamiflu and public health policy must have worked."
Isn't this was happened with the Millenium Bug....did it really exist???
Richard Nicholl
Consultant Neonatologist, Northwick Park Hospital, NorthWest London Hospitals NHS Trust, Harrow HA1 3UJ
RCPCH Tutor ,
FY2 Programme Director
secretary 8am-4:30pm: 0208 8693941
NNU: 0208 869 2900
bleep 325
email: <mailto:[log in to unmask]> [log in to unmask]<mailto:[log in to unmask]>
-----Original Message-----
From: Evidence based health (EBH) [mailto:[log in to unmask]<mailto:[log in to unmask]>] On Behalf Of Owen Dempsey
Sent: 24 September 2009 18:08
To: <mailto:[log in to unmask]> [log in to unmask]<mailto:[log in to unmask]>
Subject: Re: Do the antivirals reduce mortality in flu?
Agree with Bens comment: EBM important and should guide policy, however It's a shame that EBM continues to be hijacked and used to justify top down public health policy. I think Neal's almost throw away comment:
"Both the population and the individual perspectives (and nota bene the plural) seem to me to be entirely legitimate."
carries dangers based as it is on a false premise. Thus: The idea that all views on e.g. use of Tamiflu; [i.e. the competing views that either 'everybody' should have Tamiflu (as under the criteria of the guidelines) versus the decision/choice that Tamiflu is too risky for a given healthy individual and shouldn't be prescribed or taken] are of equal moral status, is flawed. This liberal 'all views are fine by me' stance assumes that everybody has equal access to and understanding of the 'real' state of affairs when it comes to the risk benefit ratio of this intervention. This is akin to pretending that we live in a 'real' democracy (which is of course an impossible fiction to attain) instead of an 'organised democracy where the outcomes e.g. of elections are preordained and the 'people' misinformed.
With Tamiflu, the government, health spokesmen and the drug industry - with the help of the corporate media conspire to mislead the public by over-egging the dangers of e.g. Mexican/Swine Flu and overstating (even if it is by implication i.e. simply by recommending its use) the benefits of Tamiflu. We actually know that the evidence of benefit is weak and benefit is small; and there are continuing anxieties about harms especially in the young, but we choose to ignore this knowledge. (ref. Carl Heneghan et als excellent journal club report in the BMJ rapid responses in the last 2 years or so). The knowledge for EBM is there but we are manipulated with falsehoods, therefore the choices/decisions people are making, including professionals, are 'forced by public policy' and are based on a deceit, so it is ridiculous to say all choices have equal value. What can be said is that most people are making choices that in part maintain the status quo of a society that is still exploitative, and in part simply makes profits of one sort or another for politicians, drug companies and the self esteem of the medical profession. A bit more honesty about the evidence from public health and our esteemed spokesmen would be welcome.
By the By:
Zizek talks about the Theories of Fiction of Bentham and Lacan's notions on democracy in his book Sublime Object of Ideology. Is it a necessary that society believes in the fiction of public health policy? Is it true to say that here is no such thing a society, or, that a fully paid up member of society that believes unquestioningly in public health policy is like a good Stalinist, 'made of special stuff' that special stuff being Lacan's 'petit objet a', a surplus left over as desire tries to fulfil fantasy, it doesn't actually exist. It's a lack. People try to make up for this lack by conforming AS IF the fantasy were true. If you don't believe in public health policy then you are no longer a bona fide member of society (but a dissident to be outcast or ignored). People take Tamiflu, Doctors prescribe Tamiflu (not because they expect any noticeable benefit but because they fear what might happen if they don't) and they get better, and the epidemic subsides; and everybody has been a good citizen and so thus proves that the Tamiflu and public health policy must have worked.
Best wishes
Owen
-----Original Message-----
From: Evidence based health (EBH) [mailto:[log in to unmask]<mailto:[log in to unmask]>] On Behalf Of Djulbegovic, Benjamin
Sent: 24 September 2009 14:38
To: <mailto:[log in to unmask]> [log in to unmask]<mailto:[log in to unmask]>
Subject: Re: Do the antivirals reduce mortality in flu?
Niel, no doubt the efforts like these should be commended and appreciated...
Just quick comment on your remark "The caveat is that this topic is, in some circles, controversial."
This is in fact even more important reason to develop evidence profiles/decision aids. Knowing what we know and what we don't know (and how good is the quality of our knowledge) is what EBM is all about, as you well know it.
Tom Jefferson has done a lot of work synthesizing the evidence on the effects of flu vaccine. Tom: have you created evidence profile (or, even decision aid) that it can be shared with the public? (BTW, one of the reasons that Cochrane reviews are not being used as they should is because until recently they have not included Summary of Evidence/Evidence Profile tables.)
Thanks to both of you on working on such an important topic
best
ben
From: Maskrey Neal [mailto:[log in to unmask]<mailto:[log in to unmask]>]
Sent: Thursday, September 24, 2009 8:56 AM
To: Djulbegovic, Benjamin; <mailto:[log in to unmask]> [log in to unmask]<mailto:[log in to unmask]>
Subject: RE: Do the antivirals reduce mortality in flu?
Thanks Ben, I'll file that appraisal in my revalidation folder :)
The response has been very positive and we're grateful to this group for all the inspiration.
I strongly suspect we won't get lots of clinical outcomes-based effectiveness data on swine flu vaccination in time for the early programmes, but it would perhaps be worth us taking a look again at the existing data (such as it is) on vaccination for seasonal influenza. The caveat is that this topic is, in some circles, controversial.
Bw
Neal
________________________________
From: Djulbegovic, Benjamin [mailto:[log in to unmask]<mailto:[log in to unmask]>]
Sent: 24 September 2009 13:14
To: Maskrey Neal; <mailto:[log in to unmask]> [log in to unmask]<mailto:[log in to unmask]>
Subject: RE: Do the antivirals reduce mortality in flu?
Neil, this is great! Have you (or anyone else) developed a decision aid for flu vaccine? With this panic about getting any possible vaccine one can get, it would be nice to have similar aid (of reason).
Thanks
ben
From: Evidence based health (EBH) [mailto:[log in to unmask]<mailto:[log in to unmask]>] On Behalf Of Maskrey Neal
Sent: Monday, September 21, 2009 10:32 AM
To: <mailto:[log in to unmask]> [log in to unmask]<mailto:[log in to unmask]>
Subject: Re: Do the antivirals reduce mortality in flu?
Sorry list, two postings in the same day is too much I know. Do these help, Martin?
We've trawled the literature for oseltamivir to produce the best patient decision aids we can. You can access them via the link from our home page here <http://www.npc.co.uk/> http://www.npc.co.uk/
.....or directly on our NPCi e-Learning site here <http://www.npci.org.uk/therapeutics/infect/commonintro/patient_decision_aids/patient_decision_aid1.php> http://www.npci.org.uk/therapeutics/infect/commonintro/patient_decision_aids/patient_decision_aid1.php
It's not great data but the best we can find. If you can find better please tell us, but the UK national committee haven't.
In terms of decision making, values matter. National or regional public health values (driven by onerous responsibilities to see the health system optimally prepared, no avoidable catastrophes, disruption to essential services avoided / minimised, and an excess of flu related deaths at least as low as other developed countries) would indicate wide use of oseltamivir as being entirely reasonable despite the data being limited, at least in some patient groups. The trade off is the remoter risk of future resistance and the cost - but the swine flu is now and the resistance is a future possibility. Cf clopidogrel in ACS, any antibiotic prescribing for RTIs and many more examples.
Individuals (patients and clinicians) might make different choices based on their perspective and values, none of which are likely to be exactly the same as each others. And we might all make a different choice when we actually have the flu, or someone we know has had flu-related pneumonia or worse, as opposed to dispassionate discussions when we don't.
Australian hospital docs on a recent UK documentary were apparently also all for taking an antiviral too, based on the unavoidable problem that looms large in their values. They were most worried because no one can say at presentation whether an individual will be one of the many who will have a mild uncomplicated illness or be one of the few who gets very very very sick. We seem to be hard wired as humans to be prepared to treat lots unnecessarily to reduce the risk of an error of omission. That's one of our ways of dealing with stochastic uncertainty.
Both the population and the individual perspectives (and nota bene the plural) seem to me to be entirely legitimate.
Bw
Neal
Neal Maskrey, National Prescribing Centre, Liverpool UK
________________________________
From: Evidence based health (EBH) [mailto:[log in to unmask]<mailto:[log in to unmask]>] On Behalf Of Brian Alper MD
Sent: 21 September 2009 14:06
To: <mailto:[log in to unmask]> [log in to unmask]<mailto:[log in to unmask]>
Subject: Re: Do the antivirals reduce mortality in flu?
It depends on what outcome you are promoting the antivirals for:
If for mortality - there is observational evidence for seasonal influenza for hospitalized adults
If for duration of illness - there are randomized trials (seasonal influenza)
If for other complications - there some randomized trials (seasonal influenza)
If for reducing transmission to others - I'm not sure of evidence for "treatment" but there is evidence for prophylaxis
Brian S. Alper, MD, MSPH
Editor-in-Chief, DynaMed (www.ebscohost.com/dynamed <http://www.ebscohost.com/dynamed> <http://www.ebscohost.com/dynamed>)
-----Original Message-----
From: Evidence based health (EBH) [mailto:[log in to unmask]<mailto:[log in to unmask]>] On Behalf Of Martin Dawes, Dr.
Sent: Monday, September 21, 2009 8:59 AM
To: <mailto:[log in to unmask]> [log in to unmask]<mailto:[log in to unmask]>
Subject: Do the antivirals reduce mortality in flu?
Sorry
Naïve question but I could not find any RCT's - am I missing something here or are we promoting unproven therapy?
Thanks
Martin
(neuraminidase and influenza and mortality) AND (randomized controlled trial[Publication Type] OR (randomized[Title/Abstract] AND controlled[Title/Abstract] AND trial[Title/Abstract]))
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