Adverse drug reactions (ADRs) are a massive burden on the NHS, and a significant cause of morbidity and mortality. When I worked on a cardiology ward, one of the more serious ADRs that occurred was severe haemorrhage associated with streptokinase. Rather than dying of a heart attack, the drug we gave to patients to improve their chances of survival would on occasion be the reason for the demise of the patient due (for example) to a cerebral haemorrhage.

The NPC recently reported on a systematic review of incidence and nature of in-hospital adverse events. The full paper is available as a free-access article at Quality and Safety in Health Care. The NPC note that the study shows:

• The median overall incidence of adverse events was 9.2% with a median percentage preventability of 43.5%.
• The median percentage attributed to medicines was 15.1% (interquartile range 11.9 to 20.4).

The NPC argue that this is in-line with a NPSA report Safety in doses: medication safety incidents in the NHS which they say showed that “between 3.5% and 9% of hospital in-patients experience harm from medicines.” However 15.1% of 9.2% is 1.39%, which is outside the range of the NPSA report. Thankfully, there is another well-conducted study due to be published later this year by the same group that published the 2004 BMJ paper on drug-related admissions to hospital. From what I have seen in presentations, the incidence is more in line with the NPSA report. It is possible that studies which are primarily focused on drug therapy have greater sensitivity to adverse effects of drugs than those which attempt to catch all patient-care events.

Another point worth discussing about the NPC blog post their view on the impact of the study:

The Impact
Adverse events related to medicines are a serious health issue. They cause levels of mortality higher than more high-profile health problems such as breast cancer or AIDS. In addition to the harm caused to individual patients, they also place a significant burden on healthcare resources.

The source from this comment arises from the report To Err is Human, an influential, and often cited, IOM report from 2000. The executive summary uses this comparison:

More people die in a given year as a result of medical errors than from motor vehicle accidents (43,458), breast cancer (42,297), or AIDS (16,516).

I’ve used similar statements myself in order to shock health care professionals into accepting the burden of ADRs as important and worthy of their consideration, but these sort of statements can also feed into some of the more deranged, but not totally uncommon, rants about Big Pharma. Here’s a relatively extreme example from JABS, the UK’s leading anti-vaccination site commonly linked to by the BBC:

big pharma and bad doctors have killed more people than wars in the last 50 years.

For gods sake what more corruption, cover ups and evil does big pharma have to do beside kill a million each year so these sick trolls will stop acting as as shills for them.

Who would you listen to , a mad sick corrupt troll who showns sociopathic tendanicies who thinks its fine for big pharma to commit genocide or real non corporate doctors and scientists who actually care about humanity and big pharma genocide and corruption.

I think sensible discussions about the harms of medicines need to avoid feeding into this meme, and documents like To Err is Human can unfortunately be used by opponents of evidence-based medicine to attack the use of prescribed drugs. What’s missing is the difference between breast cancer and prescribed drugs.

The difference between breast cancer, and the adverse effects of drugs, is that drugs have beneficial effects that, on balance, outweigh the risks they pose to society. For individual drugs when the risks are found to outweigh the benefits, then action is taken such as withdrawal of the drug. There is no corresponding benefit to having AIDS or breast cancer.

Every day individual patients make decisions about risk-benefits when they chose to take a medicine or not. Of course, many could be better informed about that risk-benefit balance, but overall the majority chose to accept the risks for the benefit they will receive. Sometimes patients will accept more risks than regulators think they should. Medicines are more like cars. There is a benefit from the mobility and personal freedom that cars give individuals, which seem to make death in car accidents relatively less important than knife crime, despite the massively higher numbers of deaths in car accidents (I accept the issue of intent makes a difference in this area).

The issue of preventability is also difficult. Some drugs increase the odds of experiencing an adverse event. Not all events will therefore be avoidable. Aspirin increases the risk of a gastric bleed. So not all gastric bleeds could have been avoided if aspirin had not been prescribed.

There is also the issue of monitoring: Coleman et al’s paper in the BJCP neatly explains the lack of evidence for effective methods of monitoring for harms of treatment. Here’s another cardiology example, which I also regularly saw, which Coleman uses to illustrate the difficulties of devising monitoring periods:

The incidence of hyperkalaemia in patients treated with spironolactone for heart failure seems much greater in practice than in the randomized controlled trial that showed the value of the treatment. This seems unlikely to be simply a problem of monitoring. In general terms, patients in clinical practice are sicker and less frequently reviewed than in clinical trials and therefore it is not surprising that in many examples the rate of adverse effects is higher in actual use when compared with the rates seen in the trials. Real patients may also be less likely to adhere to a stringent monitoring scheme, or more likely to have concurrent ill health that increases the chances of finding an abnormal result that is not due to the adverse reaction, or older than trial patients, and perhaps as a consequence more rapidly susceptible to the adverse drug reaction, so that the time between a reaction first being observable and it causing irreversible damage may be shorter. It raises the question of how to devise safe monitoring schemes that will remain effective when treatments move from clinical trials to general use.

So preventability can be in the eye of the beholder, and that eye is often trained on the events using a retrospectoscope, armed with more information, and time, than the clinician making the decision that led to the adverse effect.

And some adverse reactions are not preventable. Take streptokinase, discussed at the start of this post. Even with a perfect diagnosis, and evidence-based treatment, fatal adverse effects can occur. However, on balance streptokinase saved more than it lost, and this should be acknowledged when talking about the harms of medicines.

I am one.

Mobileme sucks in comparison to Gmail.

Photo from iboff.

That is all.

There’s a new website where you can leave a review of your doctor called iwantgreatcare.org. It has already been formally warned by libel lawyers acting on behalf of thirty-seven GPs, of the potential for defamatory comments to be posted by the public. There are some nice comments there too:

Many years ago he literally saved my life and has continued to be the best family doctor I have ever met.

and

Caring understanding, Intelligent and sensitive, Top Professional.

I’m not sure how useful such patient anecdotes are, take this one for example:

He was held in very high regard by the overwhelming majority of his patients. He was also respected by fellow professionals. His patients appear to have regarded him as the best doctor in Hyde. His register was full and there always seems to have been a waiting list. Patients liked him for a variety of reasons. Many would say that he ‘always had time’ for them. His surgeries overran but no one minded because they understood his wish to take whatever time was necessary for each patient. He never hurried them out. He always had time for a few words of a personal nature. Elderly patients and their families were particularly grateful for his willingness to visit at home.

That, you may have guessed, is Harold Shipman.

One of the most interesting comments from the owner of the new rating site is this:

The vast majority of comments have been positive -interestingly, the small number of spoof and malicious comments we have received have been traced back to doctors.

Very strange.

According to some of the more wacko-stalker elements of the UK’s anti-vaccine movement I am part of a government/pharmaceutical industry conspiracy to suppress the self-evident harms of vaccines. Supposedly, Ben Goldacre, Richard Horton and I comprise a supporting act to Roy Meadow in this regard. I am also alleged to be a shill for the industry, presumably paid. An accusation also leveled at me because I am able to use HTML and install Wordpress.

I have to say, this is news to me, flattering though it is to be linked to the editor of the The Lancet, who I do not know, and Ben Goldacre, who I have never met, but know through the internet because of his excellent blog.

So why do these people see conspiracies, where none exist? Charlie Booker explains in relation to the 911-truther movement:

recently I’ve found myself bumping into people - intelligent, level-headed people - who are sincerely prepared to entertain the notion that there might be something in some of the less lurid 9/11 conspiracy theories doing the rounds. They mumble about the “controlled demolition” of WTC 7 (oft referred to as “the third tower”), or posit the notion that the Bush administration knew 9/11 was coming and let it happen anyway. I mean, you never know, right? Right? And did I tell you I’m the Emperor of Pluto?
[...]
Embrace a conspiracy theory and suddenly you’re part of a gang sharing privileged information; your sense of power and dignity rises a smidgen and this troublesome world makes more sense, for a time. You’ve seen through the matrix! At last you’re alive! You ARE the Emperor of Pluto after all!

It should come as no surprise that one of the leading threads in length and numbers of readers in the UK’s leading anti-vaccine organisation’s forum is called “Debunking the Aids virus myth”.

The BMJ publish a study this week on multiple vaccinations in British soldiers. Multiple vaccines have been suggested to be linked to ill health following the 1991 Gulf war. Murphy et al examined soldiers deployed in Iraq since 2003.

Personnel who reported receiving two or more vaccinations on a single day were more likely to report symptoms of fatigue (adjusted risk ratio 1.17, 95% confidence interval 1.05 to 1.30), show caseness according to the general health questionnaire (1.31, 1.13 to 1.53), and have multiple physical symptoms (1.32, 1.08 to 1.60). These associations were no longer significant when number of vaccinations recorded in individuals’ medical records was used as the independent variable.

So individuals’ recall of the vaccinations received is not reliable, in comparison to medical records. Receipt of multiple vaccinations in UK armed forces personnel before the 2003 Iraq war has not resulted in adverse health consequences.

There are two issues here, one is that no harm was caused by multiple vaccines in the 2003 Iraq War, and therefore any association found between multiple vaccinations and ill health following the 1991 Gulf war may equally affected by such recall bias. The fear of multiple vaccines is a common lay concern expressed in the media, and by anti-vaccinators, based on limited understanding of the immune system, it is not unsurprising that the finger of suspicion was pointed at vaccines.

The second issue is that of recall bias, which Orac discusses in his reporting of the BMJ paper. He lists four conditions relating to the exposure or health outcome which can worsen recall bias.

• The event under study is highly significant in the life of the subject (such as cancer).
• The patient has a preconception that the exposure and the health outcome are related.
• The media reports an association between the exposure and the health outcome.
• The exposure or behavior are socially undesirable or illegal.

The first three points above apply to varying degrees to the alleged association between MMR vaccine and autism. Autism has a large emotional impact on the lives of the parents, there is a section of the public that has uncritically accepted the MMR vaccine-autism hoax, and finally, and perhaps most importantly, the UK media has irresponsibly reported on MMR vaccine for years. The effect of the media reporting of MMR vaccine on recall bias has been examined.

Andrews et al examined the issue of recall bias in their 2002 Recall bias, MMR, and autism paper in Arch Dis Child. They compared parents recall of the onset of autism with regressive symptoms, before the publicity surrounding Wakefield’s 1998 paper and after such publicity had become common place. The onset was recalled as occuring nearer to MMR vaccine administration in parents of children diagnosed after the negative publicity surrounding MMR vaccine, than in those parents of similar children who were diagnosed prior to the publicity.

People may take pride in the fact they don’t believe everything they read in the papers, but bias can be introduced into one’s perceptions by exposure to media reporting of safety concerns. In that respect, scare stories about vaccines can become partially self-sustaining, despite a lack of robust evidence to justify such stories.

This blog has previously noted the role of patient groups in lobbying for the use of new drugs in the NHS, and the financial relationships that can exist between them and the pharmaceutical industry. Such relationships should be transparent, but are often not noted in “Patient group demands drug X stories”.

Some of you may be familiar with Dr John Briffa, a doctor who has abandoned the challenging world of evidence-based medicine to embrace a career as a media doctor with an apparently thriving private practice in “nutritional and naturally-oriented medicine”. He advocates dietary treatment for autism with little evidence, lends his name to weird vitamin supplements for diabetes (hold that thought), and is, despite all the evidence to the contrary, still convinced that MMR vaccine is linked to autism. Perhaps most damningly of all, Dr Briffa is taken seriously by Prince Charles.

Dr Briffa has now also turned his attention to patient groups, in particular Diabetes UK. Dr Briffa is slow on the uptake. I left an electronic response concerning Diabetes UK on the BMJ website 5 years ago:

Diabetes UK are reported in the BBC-online’s Health section to be opposing the NICE guidance on the use of glitazones in Type 2 Diabetes. NICE advise that glitazones should be reserved until other treatments have been tried, such as sulphonylureas and metformin.

Diabetes UK’s spokesperson said: “Doctors and patients need to have access to the treatments that are best for them. Today’s ruling will deny that.”

“Diabetes is costing the NHS millions of pounds a day, much of which is spent on treating the long-term effects of the condition, many of which could be prevented with early, effective treatment.”

Diabetes UK has recently alluded to its transparency and accountability with regard to corporate sponsorship. In 2002 they received £750,000 from pharmaceutical companies.

I am unable to ascertain from their website whether any of these funds are provided by the manufacturers of either glitazone currently on the market. It would be helpful if Diabetes UK could have a list of corporate sponsors on their website.

Dr Briffa’s concerns are qualitatively different from mine. Dr Briffa believes Diabetes UK are deliberately advising diabetic patients to consume a diet that worsens their diabetes. This will then led to them to take more medication supplied by the drug companies that fund Diabetes UK. Dr Crippen asks if Dr Briffa has taken leave of his senses, and Pyjamas in Bananas has put up a post entitled: Briffa demented loon: Official.

There is a point at which evidence-based skepticism about the pharmaceutical industry crosses over into cynicism. That’s not all bad, cynics serve a useful balance to the industry. Further on, if one allows one self to be sucked in, one can cross the event horizon from cynicism to the black hole of conspiracy-addled ranting. Once over the line, few seem able to claw their way back to sanity.

A report in The Independent notes that measles is now endemic to the UK. Incidently they include a picture of a child and mother being threatened with a vaccine, why not a picture of a child with measles? Ben Goldacre comments.

I cannot believe the mainstream media are trying to blame this on Wakefield instead of themselves. This is beneath contempt.

The Independent seem amazing blind to the media’s influence. They wrote this in March of this year:

One of the greatest puzzles of the saga is what has sustained this level of mistrust in the medical authorities. Unlike most scientific controversies which flare up and die away, this one has simmered for a decade – and is now to be fired up again by the GMC case.

In 2004, they stated in a leader the following about Wakefield:

Are we wrong to detect the distant whirr of the same spin spin machine that so recently set about destroying the reputations of David Kelly, Andrew Gilligan and others?

In other news Oliver Kamm notes Melanie Phillips’ poor performance on MMR vaccine and intelligent design. Her continued reporting on MMR vaccine, her reliance on far-right junk science journals, and her views on science in general, mean that any statement on any matter is probably suspect if it involves logical thought. She may have been a great journalist in the past, she won the Orwell Prize for journalism in 1996, but I wouldn’t trust her to accurately tell me if it was raining. The rain is probably a scientific conspiracy to sell umbrellas or something.

They say as you get older you move from the left to right, Melanie Phillips seems to be taking that extra step further to lunacy.

The following communication has been sent from the Zimbabwe Association of Doctors for Human Rights (from Normblog).

Cases of Systematic Violent Assault and Torture Overwhelm Health Professionals

17 June 2008

ZADHR is deeply concerned about the continuing violent trauma being inflicted on the Zimbabwean population. The escalation in numbers and severity of cases of systematic violent assault and torture during May was of a scale which threatened to, and for brief periods did, overwhelm the capacity of health workers to respond. Both first line casualty officers and specialists, especially surgeons and anaesthetists, to whom patients were referred had great difficulty in adequately managing the burden of serious physical trauma.
Continue reading this post…

The Daily Mail influenza vaccine kills people story has an interesting background. Looking at Hansard, it is apparent that the data the story is based on came from a written answer to a question posed by Sandra Gidley MP (Liberal Democrat). The question and answer by Dawn Primarolo are here:

To ask the Secretary of State for Health (1) how many people died in each trust as a result of receiving an influenza vaccine in each of the last five years;

(2) how many people were admitted to hospital in each trust as a result of receiving an influenza vaccine in each of the last five years.

Sandra Gidley is known to me professionally, since we are both pharmacists and have an interest in the future of our professional body. We have met on several occasions at professional meetings, and I have found her an intelligent, interesting, and sensible individual. She also runs a blog called Romsey Redhead, which appears in my sidebar. I have emailed her to ask about her concerns about influenza vaccine, and her reaction to The Daily Mail scare story.

After being told of a death after the use of influenza vaccine, she decided to find out the facts on and figures on reported deaths and other serious reaction to influenza vaccines. She suspected that far more people would have died of flu had they not been vaccinated but wondered if there was merit in examining the deaths to see if the advice about giving the vaccine needs to be refined in any way.

The Daily Mail obviously picked up on the question and spent some time talking to Sandra, who made the point that the deaths “had to be set in the context of how many flu deaths may have been prevented”. She also suggested to the journalist that given the age of the recipients a number of deaths could have been pure coincidence. However, it was fairly clear what sort of story they wanted to write. It is because Sandra Gidley was too sensible and avoided sensationalism that the The Daily Mail decided not to include any comments from the person who made the very information request they were reporting on, and certainly didn’t raise her name. You can imagine their disappointment.

So, let’s make it clear. The Daily Mail trawls for bad news stories about vaccines, and then will willfully ignores the comments from the person who raised the concern in the first place.

As regulators become more transparent and provide information, can the media be trusted not to misuse the data? Not if it gets in the way of a nice juicy anti-vaccine story.