I'm going to talk to you about conflicts of interest in medicine and that this toolkit posed a number of questions.
I just want you to think about where your position is, what you think about some of the issues,
whether you think the relevant, whether you think they're important, and particularly at the end, what we should do next.
So this is I'm going back in to 99, 2000.
I qualified as a doctor, as a health officer in the John Ratcliffe Hospital.
And at the time, Jeff Aronson, who's here with my consultant at the time when I was a health officer and for about a few years,
that and one of the treatments that was very visible and coming to the market at the time was this treatment, which is roughly cock sip or Vioxx.
It was known at the time. And one of the things about Vioxx is it was similar to non-steroidal anti-inflammatory drugs,
but it was promoted because it reduced the risk of gastrointestinal bleeds, but was marketed as an effective pain relief.
And this is one of the seminal papers published in the time it's called the Vigo Study Group.
You can see that in 2000 in the New England Journal of Medicine.
And I just wanted to tell you a little story about some of the things that
happened in the trial and what life was like in the 2000 in seems like yesterday,
but 20 years ago. So one of the things about the Vioxx trial is Michael Warren was actually worked as a rheumatologist
at the Brigham and Women's Hospital in Boston and he became chair of the safety panel.
So any trial has a safety panel, but at the time, nobody knew this.
At the time, he owned £73,000 of Merck stock who were involved in producing roughly Cox.
Then he participated also in the Merck Speakers Bureau and gave presentations in the summer of that year.
And not only was he the safety monitoring the chair at that meeting also and this came out after nobody knew this in 2000,
they had a merck employee present on the chairing panel.
Now, one of the things is with roughly Coke said is it was not more effective in leaving symptoms of rheumatoid arthritis,
but did halve the risk of GI events, which is important because if you had a similar treatment like that and it reduce your risk of bleeding,
it would be very important for people who had debilitating pain at the time and rheumatoid arthritis at that time is before the immunotherapy.
So there were lots of people with debilitating problems,
but there was also this evidence of an increased risk of myocardial infarction, a relative risk of five, five, ten fold more likely.
And it was statistically significant. Now, when this result came out, it went to Edward Skolnick, the company's chief scientist,
who wrote in an email and this is all came out about five years later in terms of litigation.
It is a shame, but it is a low incidence and it is a mechanism based as we worried it was.
So they sort of thought there was a mechanism in there in terms of thrombotic.
But you were on an introduction to be a see cause evidence based practice.
So here's some of the things that actually happened and here's how this result didn't make it into the New England Journal paper.
Did you think which of these are appropriate? The first thing is the interim analysis had different termination dates.
The GI events were accounted for one month longer than the cardiovascular events.
Three additional images occurred in the roughly cocktail group in the month after, when the data was not collected for the CV events.
They were not reported in the paper harm with further minimised by post-hoc subgroup analysis on indication for aspirin prophylaxis.
So did a subgroup of people who were on aspirin and were on aspirin.
They also presented the hazard ratio. Instead of saying it's five times more likely,
they flipped it the other way around and said Naproxen was the intervention group and
the relative risk with point to 0.120.7 and didn't give the absolute number of events.
And although the other results were presented a profiler of the intervention group, so they flipped it for that result.
They also proposed in the paper a naproxen hypothesis suggesting that roughly Cox SIP had not been harmful,
but that manipulates into being protective and therefore naproxen is a treatment of choice because it's cardiovascular protective.
Now, coming back to Weinblatt, one of the things about one about remember he had said we need to approve this plan and how we prevent a revolt.
He's on the safety committee now. He was told about the Cut-off date one month before the study ended.
Weinblatt agreed. As a result of the Cut-off date,
three of the 20 heart attacks among the five patients weren't included when wrote up the study in the New England Journal.
And it looked safer than. Lee was so not doing the five times it came down.
So soon after agreeing to the plan, Weinblatt signed a new consultant contract to sit on a merck advisory board,
paid him $5,000 a day for 12 days over a two year period.
He received an initial check for $15,000 a few weeks later.
Now, this never came out until four or five years later because at the time we didn't have the
same competing interests that we even thought he was involved with Merck at the time.
It's not a bad paycheque, is it? If you can get it $60,000 a year.
12 to 80 is not bad. Now, one of the things that then happened is the FDA took quite another time.
They took another year. So it was until 2001 till the FDA started to get their act together.
But Merck had a relentless series of publications, press releases and time.
Merck reconfirmed favourable cardiovascular safety of Vioxx, complemented by numerous papers with a million reprints by the New England Journal paper.
And the company sponsored countless medical education events and symposium at national meetings to debunk the concerns about Vioxx.
And it was this message with reinforce that roughly. COX It had no cardiovascular toxicity.
Rather Naproxen was cardioprotective. And I can remember that message carrying on into about the middle of 2001 two.
And then all the studies started to become published.
There were serious issues, and it took about another four years to about two, four, five for people to really go to town.
And this is in 2008 from people like Catherine DeAngelis, who was editor in chief of John I think at the time.
And you can see Jo Roth, who still works in the US,
that most of the trials were written by Merck scientists or go go through written
by contract workers disguised the names of academically affiliated doctors,
recruited as named authors. And that was my journey for like the 20 year journey of thinking.
Competing interest really do make a difference. I've been involved in the direct prescribing of violence in 2000 2001.
I can tell you there were significant numbers of pharmaceutical representatives camped in hospitals,
taking junior doctors out for lunches and dinners. And I think it's interesting that evolution and here's a paper in 2000 in JAMA
showing that there was quite a significant amount of evidence already emerging.
There were 29 studies that had already found that were looking at competing interests in the issue of physicians in the pharmaceutical industry.
Is it gift, image of the gift? And one of them it is worth having a look at.
And that just came out a year later with this one of principles and pens.
Quite nice, nice title, isn't it, for a study actually.
Attitudes and practices of how staff working towards industry promotions.
So what this study is, what it did is we looked at about 117 residents and did a survey of them and
started to ask them about some of the stuff that was going on across the board.
So interesting. The first is this is is it appropriate or somewhat appropriate for you to receive this gift?
Okay. Top nine types of promotion assist.
So you can see receiving an antibiotic card, about 90% said, okay, conference, lunch, dinner, lecture, article ten, all scored very highly.
Then you get to about 60 70% for a social outing seminar attended to say yes textbook and see me trip
and then I was right down here about 15% think it's alright to have luggage what that luggage is for,
I'm not sure. But the next slide though is incredibly interesting.
Now this is the perceived influence of representative sample prescribing practice.
So I receive money. Yeah, I'm the grey box.
Yeah. So if it's. If I'm receiving a gift, I think there's no influence on me.
However, if you receive a gift, you're in the bullet box.
So if you receive a gift, it causes a lot of influence on you, but it never causes any influence on me.
And I think that's a really interesting because anybody you'll ever talk to
about competing interest in conflict will always say It has no effect on me,
but boy, does it have an effect on you. The comp of can't be right, can they?
And so of course it cannot be the only other people are influenced by promotion and not me.
And so there's also data at the time and I remember this and there may be there probably only for everybody.
It's a bit younger 20 years ago in the room, but what they'll remember at the time is as you walk around a hospital, many of the things that you.
On a daily basis was somehow given to you. And one of the things that I would remember were tourniquets.
So we would carry lots of items and we'd have our white coats and be stuffed full of items.
And actually what you can see in their mittens when they start this residence in the Kiama also they found the percentage that actually had commercial
branding on and so 30% a reflex hammers had some commercial branding on and there were all these even a stethoscope tab with up to 50% penlight.
And you can see by the time you get to a reference book, somebody had given it for free and it had a commercial branding on.
So we were like basically we were like, when you see the motor drive nowadays with commercial stock all over us, that's what we were.
Now, even more so when you look at the this the disparity between patients and physicians.
So when we talk about the percentage that consider the gift inappropriate, whatever that gift is,
you can always see that patients think it's far more likely to be inappropriate compared to physicians and that when they think it's influential,
patient, think it's far more influential than clinicians do.
And I think there's a complete disparity in how the public viewed what's going on compared to
within when clinicians take a guess whether it's influential or whether it's inappropriate.
Now, this is the pit that comes in within the pit, and I think this is the cat's paper in 2003,
all gifts large and small towards an understanding of the ethics of pharmaceutical industry gifts.
The obligation to directly reciprocate whether or not the recipient is conscious of it tends to influence behaviour,
feelings of obligation and not related to the size of the initial gift or favour.
That position is eroded by a significant number of people who receive gifts, considering there is no relationship and no reciprocation.
And I think these messages were clear in the early days.
Now it was discussed and if you're not really sold on, the idea of, well, industry sponsorship has an impact.
I think this paper by Deborah Barnes and Lisa Breaux is one of the best examples of why it matters.
And this is a review articles on the health effects of passive smoking that reach different conclusions.
And then conclusions is passive smoking is not harmful or passive smoking is harmful.
Now, if you look at the data, you can see that passive smoking harmful.
If you consider it's harmful. Out of 31 offered,
only two who are affiliated to the tobacco industry think it's harmful compared to 87% who are not affiliated to the tobacco industry.
The passive smoking is not harmful. You can say it's the other way around and if you calculate the odds ratio on that,
you end up with an odd ratio of 84 or affiliation being the most likely impact on the results of whether it's harmful or not.
And I think, you know, we all think now, well, the regulations change something in the regulatory position if we don't smoke in places because
we are pretty clear that passive smoking is not a good idea and it has significant impact.
But this is what was being fought again 20 years ago to establish these positions.
Now, when you think about the position and one of the things I've done is try to understand where do we made decisions along this pathway?
How do we get to our current regulatory landscape of what makes a difference, what not and what the read?
There's a confusing array of tax legislation and a confusing array of what I call policies and guidance.
So the at the top is actually legal acts that exist in US and other countries down here
is sort of guidelines and policies that try to tell us what we should and shouldn't do.
And most of them are voluntary. But the first one probably is in 1980 is the US Congre Congress Payola Act,
which required investigators to disclose financial conflicts to interested parties,
including regulators, institutional officials and funding agencies.
That was the first one that mandated any legal requirement. But you can see that was quite some time before we get into 2007, the FDA Amendment Act.
But what I wanted to do in these policies and guidance, we thought one of the most probably influential were this 209 Institute of Medicines report,
and they appointed in two over seven the Institute of Medicine appoint the Committee on Conflict of
Interest in Medical Research to examine these conflicts in medicine and trying to somehow think,
what are they? How do we limit them? Because they're out of control and they're out of control because what we've just seen in the fifth to 2000.
Two, 2005. Now, in that report, there are some very revealing pieces of information.
Data suggests that these relationships,
that's the relationship between physicians in the industry may influence physicians to prescribe a company's methods,
and even when evidence indicates another drug would be more beneficial.
Now, also within that is the public health within that for it.
I wanted to go back. I missed one out. As a general rule,
that research should should not conduct research involving human participants
if they have a financial interest in the outcome of the research as well.
And I find that fascinating. That's really quite an interesting.
That's 209 Any institution I've worked in and research institution will have a difficulty in answering
that in the affirmative if they're also in some way conflicted by taking money as a competing interest.
Now also within there is a public needs to be able to trust that physicians decisions
are not inappropriately influenced by their financial relationship with industry.
Now, this is a key principle. If you're going to do research that matters and communicate that matters.
There has to be a sense of trust.
Yet we've shown in the early stuff that the public thinks taking gifts and being involved in industry is influential and not appropriate,
whereas we think it's okay. Now one of the responses to that in the US, which I think was a huge step forward with what's called the US Sunshine Act.
Anybody aware of the US Sunshine Act right now, if appropriate,
on a day like today where Sunshine is in and in the middle of January is called the US Physicians Payment Sunshine Act,
the federal law that requires all pharmaceutical biologics and medical device manufacturers
to disclose payments and transfers of value to the US by the US teaching hospitals.
And one of the things is it makes the interactions more visible.
So it's not the responsibility of me if somebody pays me of a device manufacturer
or a pharmaceutical agent in the US and that payment is a certain amount,
then actually what they have to do is they have to tell me,
yeah, they have to report it what they've paid onto a central database and they have to
submit that to the centres for Medicare and Medicaid services on an annual basis.
Yeah. And including that is all payments of transfers of value over $10 a year would be under $10.
You could transfer me. It could do probably that. I'll give you some change for the both fair.
But over $100 means we have to report everything to the institution and you have to be required to see the bottom.
You have to report research payments made to the institutions, conducting research on the manufacturers behalf, including the names of the parties.
And that appears on a database that you can search freely.
And it includes pretty much every type of payment, whether it's educational or not.
And the impact of this is ProPublica of the proof nowadays proof doctor you get company cash tend to prescribe more brand name met and
what ProPublica did is get the data and look at the relationship of the data for payment and look at the data in relation to prescribing.
And what they found is doctors who receive payments were in general twice as
likely to be high brand name prescriber than doctors who did not receive payment.
That's where you've got a generic equivalent and you could take a branded product that obviously cost you more for no added benefit.
But in addition to that, there is a very high and if you get to the very doctors who receive payment with 2 to 3 times as
likely to have a very high net brand name prescribing than those who did not receive payments.
And what we're seeing is a very small number of doctors can be responsible for a lot of
high level prescribing and have been recently aware of that in the opioid crisis as well,
that actually much of the high prescribing can be down to a very small number of doctors who are highly influenced.
Now, whether that's all of them competing interests or not, we can't tell in this country because we don't have a database like this.
What we did instead is have the A BPI code, the British Pharmaceutical Institute code,
and that required pharmaceutical companies to disclose monetary value of support with a value of £250 or more.
That threshold with report proved in in in 2012.
However, it was voluntary and I was on the way here.
On the way here, Jeff and I was walking out of my office and I ran into Ben Goldacre and I said,
I'm going to I'm going to take your name in vain, Ben, because this letter he wrote to the BMJ, which was in 2014, is problems with.
A BPI proposes to release data on payments to doctors.
And he basically said the plans to release this information through its own website,
it says to provide a one stop service with Web pages for patients visiting to find about their doctors.
In reality, this will mean that a flawed and incomplete dataset is presented to the public.
The reason being is it's completely voluntary. You can have your name redacted and removed.
You have to agree. So the industry has to say, we'll put it out there.
You then have to look at it and say, I'm happy to go there. You can aggregate the data if you want and you can even say, I don't want it.
And what's happened is only about half of the people have agreed to have that data up there, and not many people have agreed to have their name.
So they may put it up there and say, you can see not, but somebody had money from Bayer and it's X, but I'm not going to tell you who it is.
And they even brought another version of this called Disclosure UK,
which is the version three, if you like, if the website plays a vital role in the development,
delivery of life and enhancing in life saving medications,
and this site says we want to ensure that patients and others have confidence that this relation is open and transparent.
And this is why the pharmaceutical industry has taken the lead on disclosing details of payments and other benefits.
I want you to think about that. Now, you could go in the research and find papers like this.
This paper by Chaya Molinari and in 2017, which looked at the disclosure data in 2015 and 16,
it said basically that key deficiencies, there's a huge problem, but you don't really need to do that.
You can do what I did last night. You can go to the database, go into Disclosure UK.
You can look at your institute, as I did for Oxford University, and look at how much money was disclosed to Oxford University.
So in 2006, now minded the the income of medical sciences in Oxford University is about 450 million, I think, right now.
And in 2016, with £478,000 disclosed in industry payments, in 2017, it was £95,000 and in 2018 it £32,000.
Anybody looking at that would either say, hey, we're in deep trouble, we're going out of business pretty quick.
I would look at it and think we're not taking it seriously. I when I call databases, when they're voluntary.
When it first came out in 2016, there's a bit of activity to try and show what you do, and it's the right thing.
That's why it's gone up. A year or two later, people have gone. Nobody cares.
Nobody's looking. There are only one or two people who can be bothered to do what I'm doing right now.
And actually why even bother in 2018? And I suspect by 2019 it be zero.
Therefore, voluntary disclosure, whatever you do, doesn't work and other countries have realised this within the hierarchy.
You can see that many Australia, how many people would know that Australia has its own Sunshine Act, France has its own Sunshine Act.
In fact, right now there is, in addition to the US, Portugal, Denmark, Australia, South Korea and France all have versions of the Sunshine Act.
And for instance, France establishes public accessibility, the transparency in health care database.
But I mean, South Korea has also seen the light in this thinking.
It's important, as we say, for trust to develop a system where people can go and be accountable and look up who's being paid.
Well, whether this is a because we think in private payment systems,
it's more important somehow there is a belief in the national health system this can't go on,
whereas in private provider systems it's like, not only are you in the back, you'll be paid more.
If you prescribe these drugs from the manufacturer, you insurance both might be influenced as well.
That could be some reason. But I was asked basically I'm one of the friends French of just published a paper by Boot Goupil and colleagues looked
at the French database and what it showed in the French database is that gifts to French GP's are incredibly common.
88% of GP's have received some gift in France and of course it's linked to poorer prescribing in those that did.
And so once you know that levels going on, you think, wow,
it's incredibly helpful to understand this and it helps the French I think think like where is all prescribing,
what are we actually trying to achieve? So coming to where we are now, look,
there's a wealth of evidence as well that interactions between physicians and the industry generally and
sales representative specifically is associated with physician attitudes and their prescribing habits.
And this is a systematic review published recently in 2017 and what it shows in there, if you can see the behaviours just here,
I think you go down the top one is gif and so it'll tell you where we've got attitude and.
Where you've got direct studies that show you there's an impact.
Drug Sample Pharmaceutical Representative Speak of honorarium research funding, conference,
travel industry paid launches, family sponsorship and interaction with sales representative.
That's what that is. And you can see prescribing behaviour out of them.
Six of them have an impact on prescribing behaviour.
Irrational prescribing is linked to pharma pharmaceutical representative speakers
and you can see doing their conference travel increase in prescribing of the sponsor
drugs increase input with industry paid launches and with CMA sponsorship and
interaction with a representative leads to higher prescription of the company joke.
Therefore, all of them are designed to do what they say they do on the ten.
Otherwise, why would they even bother? Nobody would do any of that funding if it didn't have a direct impact on prescribing behaviour.
That's what the industry knows. That's why they keep doing it.
We haven't even touched on the here within all of this of the impact on guidelines and whether that.
But there is also an impact if we looked here that if you follow the guidelines,
you'll get the decisions you want and the recommendations towards your sponsor's drugs.
Therefore, about just before Christmas, writing with Margaret McCartney in the In Lancet,
we produced this health care conflicted, confused and in need of change.
I have to say, I was slightly surprised that The Lancet took this,
but somehow that means to be potentially a bit of we need to have something in the area, because I think it's coming back.
We had a cycle in 2000 where we started. It was a huge problem.
Many people thought it was solved. But actually the problem is starting to come back in a way in different ways,
whether it's funding research, whether it's funding guidelines, whether it's coming in the back door.
But what we said in that is that we need a statutory declaration of interest by all professionals and individuals,
and that employers and regulators require annual declarations that should simply request it for essential register.
That is not that difficult. So if you were a clinician at the point of GMC registration, which occurs annually,
it would not be much to make an annual declaration of your conflicts of interest as a start.
Now I with for if you wanted to be really effective in health care and evidence based health care and taking positions,
you really should just follow things that were a good idea and basically should have been done 15 years ago.
And if you go back to 2005 is the fourth report.
Fashion Influence of the pharmaceutical industry in the House of Commons Health Committee is the report, together with formal minutes,
says in there doctors in particular key opinion leaders should be obliged to declare significant sums or gifts they receive as hospitality.
Professional bodies should maintain a register of these declarations that is now 15 years old.
That statement and has not happened. Therefore, one has to happen.
What's the purpose of the House of Commons? What the purpose of Health Select Committee?
If they make direct recommendations and they're not followed through,
what happens is they get kicked into the future and a few years later there are
other recommendations and these are put on the backburner and hopefully forgotten.
So what could you do in the face of that? I think there are two things you could do.
The first thing is if you go to university pages while we're waiting for this register, you can put all your conflicts of interest and payments.
It's been a mystery to me why universities don't say, Everybody have the bio page.
Why don't you at least keep your own conflict of interest up to date on that site?
Now, it's interesting. There is direct evidence when you go and there's a systematic review of conference proceedings.
And the average time that people put these up for is about 20 seconds and that's at conferences.
So I think when we see this and people say here my conflicts of interest,
it's like I admonish me and moving on is I think the public needs to be able to access and just go, I can see who's paying you.
It's not about me. And you think we're all right.
It's about doing for the public access to know who's paying you or not.
And I think that's important because if the NHS needs payment and I'm saying somewhat about the NHS, I'm conflicted on it.
So that's where you get the transparency of your declaration.
The second thing is this is called Sunshine UK, which Margaret McCartney is developing and I'm slightly involved in and it's going forward.
But what this does is allow you to make your own declaration as a doctor and if you have a GMC number, you can put it on there and I'm on there.
And then it allows people to find a doctor and it's a website,
the holding place while we're waiting for people like the GMC or our government to get their act together.
So I'm going to finish there with where we started.
The question is, where did we start? Should doctors with commercial interest lead research on their.
Photos. Should we forget conflicts and discuss declarations of interest and instead
who shouldn't hold them in ten conflicts of interest registers for doctors?
Should practices and doctors work with the families industry as well as serve on guideline committees?
Should researchers with extensive final interest be disqualified find from studies of their own products?
Those sorts of questions. Right now, in an ever commercial world,
we need to seriously think about and think about what should be done differently because there's a fundamental
problem at the moment if the public just doesn't trust us when it comes to assessing the evidence,
informing them about decisions and making decisions on their behalf.
Thank you very much.