I always recommend people to read David Healy’s Psychopharmacology 1, 2, and 3, together with Jack Scannell’s articles (here and here) to get a feel for exactly what drug discovery means. What is beyond doubt is that we are not as efficient at it as we once were. There is lots of blame to go around. The following gives a flavour of some of the issues ( or at least one take on the core issues).
From a review in ‘Health Affairs’ of A Prescription For Change: The Looming Crisis In Drug Development by Michael S. Kinch Chapel Hill (NC): University of North Carolina Press, 2016, by Christopher-Paul Milne.
He chronicles these industries’ long, strange trip from being the darling of the investor world and beneficiary of munificent government funding to standing on the brink of extinction, and he details the “slow-motion dismantlement” of their R&D capacity with cold, hard numbers because “the data will lead us to the truth.” There are many smaller truths, too: Overall, National Institutes of Health (NIH) funding has fallen by 25 percent in relative terms since a funding surge ended in 2003; venture capital is no longer willing to invest in product cycles that are eleven or twelve years long; and biotech companies may have to pay licensing fees on as many as forty patents for a decade before they even get to the point of animal testing and human trials….
In an effort to survive in such a costly and competitive environment, pharmaceutical companies have shed their high-maintenance R&D infrastructure, maintaining their pipelines instead by acquiring smaller (mostly biotech) companies, focusing on the less expensive development of me-too drugs, and buying the rights to promising products in late-stage development. As a consequence, biotech companies are disappearing (down from a peak of 140 in 2000 to about 60 in 2017), and the survivors must expend an increasing proportion of their resources on animal and human testing instead of the more innovative (and less costly) identification of promising leads and platform technologies. Similarly, some of academia’s R&D capacity, overbuilt in response to the NIH funding surge, now lies fallow, while seasoned experts and their promising protégés have moved on to other fields.
With many powerful academicians, lobbyists, professional societies, funding agencies, and perhaps even regulators shifting away from trials to observational data, even for licensing purposes, clinical medicine may be marching headlong to a massive suicide of its scientific evidence basis. We may experience a return to the 18th century, before the first controlled trial on scurvy. Yet, there is also a major difference compared with the 18th century: now we have more observational data, which means mostly that we can have many more misleading results.
I think the situation is even worse. Indeed, we can only grasp the nature of reality with action, not with contemplation (pace Ioannidis). But experiments (sic) as in RCT are also part of the problem: we only understand the world by testing of ideas that appear to bring coherency to the natural world. A/B testing is inadequate for this task — although it may well be all we have left.
G4S, the outsourcing company, has sold its US juvenile detention centres business for $57m. It said it had sold the business to BHSB, a US a “behavioural health care services company” that provides services to troubled young people. FT.
We know where this ends up.
Comment on an FT article. How things have changed. Even I can remember a colleague — a few years my senior — who went for a Wellcome Training Fellowship, only to be interviewed by one person, with the opening question being, ‘Imagine I am an intelligent layperson: tell me what you want to do!’
I was a war baby, a small farmer’s son and in 1960, at 17, I had a chat with my most trusted teacher about what I should do to apply to become a doctor for which I had just acquired a good group of Scottish highers. He advised me that because I should have applied a number of months before, to write a letter to the University enclosing my qualifications. I was asked to come and have a chat with the Bursar and the only thing I remember him saying was that my qualifications were good but did I realise that I might be preventing somebody else from getting in. I am ashamed to say that I replied that I was not really too troubled about that. I was accepted, and was fine.
When you want to find your way around a city, you might memorise key streets or more likely use a simplified map as a guide as you travel. But when you know a city, you navigate by being able to recall how you get from A to B. In fact you may have difficulty drawing a map — certainly to scale — but your memory is made up of lots of instances of what lies around a particular corner. Much of what you learn about diseases is the map in this analogy. By contrast, what the experienced clinician knows are lots of instances of what lies round particular corners. Those instances have a name: they are called patients.
“We have a policy to help each ward—not just the acute admissions wards, but each ward in the hospital—decide who is the ‘least bad’ patient to approach to ask to sleep on a bed in the corridor. We have a plan for which nurse takes responsibility for taking observations—they are recorded in ‘the corridor folder.’”
Other realistic medicine comments on the same BMJ page here collated from a RCP report.
For a flavour:
Now if I had to pick, I would overcome my suckerproneness and take the butcher any minute.
Incerto here. Deadly serious.
“When an older person dies, it’s harder to know that they died because of poor care,” but he added that the “families know”.
This is an article about the entirely predictable crisis in care for vulnerable people. We used to do it better, but decided cheating was more profitable. “Most local authorities buy care piecemeal via an auction system where contractors bid to provide a care package for each elderly or disabled person.” You cannot run a service on this basis; you might or might not make money. I remember being told as a young medical student: the local authority homes are the best, they have professional standards their staff have pensions, and unions etc . Avoid private providers.
The lyrics are about a cognate issue but on this topic I am always reminded of Peter Gabriel’s words and sense of disgust.
More Americans now die from drug overdoses than from car crashes or gun violence, and more than 26m are being treated for addiction, according to CDC figures.
This is the title of a piece in Nature, discussing how much evidence is needed before you bring a drug to market, and how much information you should gather after the drug is available. The reality is possibly more nuanced that is made out here, and knowing how regulation has changed and was different between countries is worth factoring in. But I think the key issue is that many people do not trust drug companies, and they are right not to do so. It was in the FT of all places, that the comparison between public perceptions of pharma and ‘the bankers’ was made. Trust has a value, a value to both parties in any exchange. And really, why do you need advertisers to get involved?
Refreshing to read an article in which I can find something to disagree with in almost every sentence. And the title — in the print edition only —‘Taking your research to the real world” was probably the work of the subeditor. But the tired trope of academia versus the real world is like a red rag to a bull (self-reference intended). Most of all, I find the belief that unless you are changing health care in the short term is some distant country, you are somehow deficient as an academic, conceited.
Capitalism has helped lift more people out of poverty than most public health researchers; economists basic work on how societies work may do the same; and I am not certain how Watson and Crick would have fared under this self-congratulatory humbug. The real danger is that we are forgetting that universities are some of the few places left to do genuinely transformative and generative work. There are plenty of alternatives for much other ‘close to market work’: private corporations; NGOs; national health agencies; consultancies. Delivery and revolutionary science belong to different scales and cultures (mostly).
The report’s authors wanted to know what drove nurses and doctors to join agencies, presuming it was simply a case of higher pay. But the researchers found that agency workers in the NHS had similar pay. What they found interesting was that agency workers felt better off because they had escaped the internal politics, the bureaucracy and the stricture of rotas that rarely matched the demands of home. As agency workers they believed they had more control over their lives and put up with less bullying from their employer.
A report by the National Institute for Economic & Social Research (NIESR) quoted here.
I have a secret admiration for some aspects of surgical training. We all know the bad ones, so I do not need to talk about them. When Lisa was doing her Mohs’ fellowship, it was the following vector: you watch X procedures, you perform Y procedures under supervision and you then perform Z procedures ‘independently’, with help on hand. After that, you keep learning. Sensible, and has the essential character of what has been known about craft apprenticeships for over one thousand years: apprentice; journeyman; master. This BMJ piece by a urologist asks:
If you were applying for a certificate of completion of training (CCT) in urology in 2015 you had to have seen or assisted in at least 20 radical prostatectomies before being signed off as competent. A year later, for no apparent reason, it appears that 10 will do.
He then goes on:
Standing in a theatre, unscrubbed, so you can say you’ve seen a procedure was never a part of surgical training, nor should it be now. It has no value. Unless you are very good at the procedure already and you are learning nuanced techniques from a master surgeon, watching a procedure will never make you a better surgeon.
Now, I despair of this sort of thing even when we ask medical students to do it. Why, is the question? What value is there, in watching? That this is considered meaningful at this level of training is even more worrying. And of course the figures will be pushed down, over time. This is the NHS, after all; never let expert judgment get in the way of a political imperative or somebody paid by the government: “we have to revise the speed of light for operational reasons….”
There is a more subtle point which makes thinking about the article even more worth while.
Trainees should spend their training doing the things that they’ll be spending their lives doing, not watching procedures they will never perform.
Now, it is clear that the current bull coming out from HEE, NHS, Deans etc is that we don’t need experts anymore, just people to cope with whatever disease is the flavour of the month (that there are demographic changes — pace the lectures I received from John Grimey Evans in 1976— was apparently not obvious to NHS managers or Jeremy Hunt till late 2016). Here is a problem.
When people finish formal training they are not as expert as they will be in 10 or 20 years. I do want an experienced dermatopathologist to be reading the samples I sent him. Wisdom is not the sole preserve of the old, but in many craft or perceptual disciplines I know about, the old guys and women do it better. So, problem one, is that when people come off a training scheme they are not the doctor they want to be. They are not qualified, they are just setting out, able to work without immediate supervision — as they choose and judge. This is the ticket.
The second problem, as the author makes clear, is that the training schemes are wasteful and not geared to excellence. Again, in a world of ‘pull’ (John Seely Brown’s phrase) the NHS is still trapped within the metaphors of the same industrial age that Donald Trump thinks is going to bring all those jobs back.
We have lost our way in much of what is important in medicine. It’s time that we focused on what really makes a surgeon better and stopped the pointless processes that surround training
Amen. But the surgeons have got some things going for them. IMHO many other branches of medicine are much, much worse.
Kenneth Arrow has died. A real economist. I have a very hard time talking most health economists seriously, especially when they think QUALYs are anything but an almighty sleight of hand over reason (contract work for the NHS). As one economist pointed out to me, one is tempted to imagine that economists who were not very good at economics, become health economists. But that may be a little unkind, and we do need clear thinking about health. Here is a link to a paper published on the economics of the health care industry in 1963. It is both deep, humble, and wonderfully lucid. The econocracy movement should champion it.
People who make predictions of how many doctors or even what specific type of doctor we need in (say) 20 years are IMHO generally deluded. Or they are telling fibs. Or selling something. The following is from the NEJM and is about ‘hospitalists’
Twenty years ago, we described the emergence of a new type of specialist that we called a “hospitalist.”. Since then, the number of hospitalists has grown from a few hundred to more than 50,000 — making this new field substantially larger than any subspecialty of internal medicine (the largest of which is cardiology, with 22,000 physicians), about the same size as pediatrics (55,000), and in fact larger than any specialty except general internal medicine (109,000) and family medicine (107,000). Approximately 75% of U.S. hospitals, including all highly ranked academic health centers, now have hospitalists. The field’s rapid growth has both reflected and contributed to the evolution of clinical practice over the past two decades.
The only way you can play ‘make believe’ like the DoH and all the NHS ‘experts’ so keen to trample all over our medical students’ futures is if you think Stalin is still alive and sorting out the tractor numbers.
Doctors seem to diagnose what they know, so find out what they know before you ask them whats wrong with you.
From an obituary of George Klein in Nature. If you have ever thought about cancer, his thoughts have touched yours.
In 1957, a chair was created for him in tumour biology, a research field that he had helped to establish. The department of tumour biology that ensued was international and influential. Most of today’s leading cancer researchers who are over 50 have had some interaction with George and his department. Seven secretaries wrangled his large correspondence. He invented social media before the technology existed.
A telling phrase:
His last book, Resistance (Albert Bonniers Förlag, 2015; published in Swedish), won the prestigious Gerard Bonnier prize for the best essay collection of that year. It deals with resistance to extremism and to cancer. Throughout his life, George was preoccupied with the thin borders between evil and good, and health and disease.
Remember the jokes about the only way to run an efficient hospital is to have one without any sick people? Well just read this, from an editorial by Martin McKee and colleagues in the BMJ. The context is what might be involved in any trade deals with the US and what US corporations would require:
They can be expected to look abroad, making the UK, with a struggling NHS, a tempting target. The UK prime minister, Theresa May, has not excluded the possibility of opening the NHS even further to them. At present, US corporations struggle to make a profit in the NHS. They would be unlikely to agree any deal that limited their ability to press for changes that would generate profits, such as excluding poor and ill people.
It was reading Herb Simon’s ‘Sciences of the Artificial’ that woke me up what some professional schools had in common. I even wrote a piece in PLoS Medicine arguing that medicine is more engineering than science (‘The problem with academic medicine: engineering our way into and out of the mess’). And I think I called it right. But the parallels between medicine and many other other traditional professions is large. I am thinking law, architecture, teaching, and engineering. These are all design sciences, or since I sort of object to this use of the word science, design domains. One of the reasons medical education — and to a lesser extent medicine is in such a mess — is the way that we have failed to grasp this distinctions. I wrote last year:
Simon was a genuine — and it is an overused word— polymath, and at that time I was ignorant of his many contributions. His work ranged through business administration, economics (for which he was awarded a ‘Nobel’ prize), cognitive science, computing, and artificial intelligence. But what fascinated me most was the content of his most famous book, ‘sciences of the artificial’. In this work Simon set out to unify and provide a common intellectual framework for many human activities that involve creating artefacts that that realise a purpose of our choosing. Unlike our dissection of the natural world, whether that be identification of a gene for a disease, or a virus that causes a human disease, Simon was concerned with how humans build artefacts. In particular how do we navigate search spaces that are large, and where uncertainty is all around, and where there may be no formal calculus to allow us to fire across boundaries. He was thinking about thinking machines of course, but quite explicitly he was concerned with the professions, architecture, law, and of great interest to me, medicine and teaching and learning. I was hooked.
One of my favourite quotes is from Simon’s ‘Models of My Life’
More and more, business schools were becoming school of operations research, engineering schools were becoming schools of applies physics and math, and medical schools ere becoming schools of biochemistry and molecular biology. Professional skills were disappearing from the faculties.…they did not fit the general norms of what is properly considered academic. As a result, they were gradually squeezed out of professional schools to enhance respectability in the eyes of academic colleagues.
So I warmed to an article titled ‘Building a future for engineering’ in the Times Higher, linking to a Royal Academy of Engineering’s 2014 report, ‘Thinking Like an Engineer – Implications for the Education System’. I have not read all of the latter, but I warm to the phrase in the THE, referring to the report: ‘Even more fundamentally, engineering is a set of habits of mind’. Clinical medicine is more engineering than science.
This is an absolutely terrific article about ‘Choosing a specialty’. It focuses on psychiatry and the particularly problems that effect psychiatry but contains many powerful insights that most medics will recognise even if you have not expressed them. Many will not admit to them, and the medical schools will look the other way.
When you ask me whether you should enter psychiatry, your question also becomes whether I would go into psychiatry once again, knowing what I know now. Most people will tell you to enter their profession for that reason. They are justifying their own decisions. Their reply to you is a means of reassuring themselves.
You should ask yourself: Is your main purpose in choosing this line of work to make a living? If it is, then you should know it is, and don’t put too much effort or care into worrying about the work. It isn’t your main purpose in life. Your main purpose in life could be your marriage, or your children, or your larger family. Or it could be another activity other than your main paid work, such as writing, or art, or music, or faith.
The it gets into the DSM….
“Trouble is, the intrusions cannot be ignored or wished away. Nor can the coercion. Take the case of Aaron Abrams. He’s a math professor at Washington and Lee University in Virginia. He is covered by Anthem Insurance, which administers a wellness program. To comply with the program, he must accrue 3,250 “HealthPoints.” He gets one point for each “daily log-in” and 1,000 points each for an annual doctor’s visit and an on-campus health screening. He also gets points for filling out a “Health Survey” in which he assigns himself monthly goals, getting more points if he achieves them. If he chooses not to participate in the program, Abrams must pay an extra $50 per month toward his premium.
Abrams was hired to teach math. And now, like millions of other Americans, part of his job is to follow a host of health dictates and to share that data not only with his employer but also with the third-party company that administers the program. He resents it, and he foresees the day when the college will be able to extend its surveillance.”
Cathy O’Neil, ‘Weapons of Math Destruction’, excerpt on Backchannel.
This sort of thing is going to be all over education and our private lives. Big data masquerading as big ideas, or just ‘big money’. Its just because ‘we care’.
I fully understand the pharmaceutical industry’s frustration with NICE – it stops them making so much money at taxpayers expense. What I don’t understand is why we are paying them any attention.
Comment from FinPhil in the FT. Most recent egregious example of pharma here, although this is not the NICE example. 2016 was the year when pharma began to boast about their new ‘we do not need to invent drugs’ financial model. Then they got embarrassed, as commentators like Martin Wolf of the FT pointed out that many people now viewed pharma like they viewed bankers. Financial engineering is much easier than biological engineering.
“Banking regulators failed and now we have no money. Does the NMC make nursing safer? No. Does the GMC make doctors safer? No. Regulators are the dust-carts that follow the Lord Mayor’s Show of life. There is an utter fiction that regulation improves anything. The catastrophes of history are testimony to that.
Health regulation fails because humans, doctors and nurses fail. They may fail because we do not support them, educate them or motivate them, fund their purpose or demand too much. We regulate activities because they are complicated or vital. That is our mistake.”
Go read, The Audit Society: rituals of verification by Michael Power.
From a review in the FT of Steve Silberman, of what sounds like a book for our time, ‘How to survive a plague’, by David France.
“Jesse Helms, the five-term Republican senator from North Carolina, personally blocked spending on Aids prevention, treatment or research for years, pontificating from the Senate floor, “We’ve got to call a spade a spade, and a perverted human being a perverted human being.”
“Some of the most haunting passages in the book record twists of fate that delayed effective prevention and treatments for years. A young chemist at Merck who suspected early on that a class of drugs called protease inhibitors might yield promising avenues for research was killed on Pan Am Flight 103, downed by Libyan terrorists over Lockerbie, Scotland, in 1988. Years passed before other researchers went down that road again, discovering a drug that became a template for the “cocktails” that have turned HIV infection into a manageable chronic illness rather than a certain death sentence.”
In 1978, the distinguished professor of psychology Hans Eysenck delivered a scathing critique of what was then a new method, that of meta-analysis, which he described as “an exercise in mega-silliness.”
Matthew Page and David Moher here in a commentary on a paper by the ever ‘troublesome’ John Ioannidis, in his article titled, “The Mass Production of Redundant, Misleading, and Conflicted Systematic Reviews and Meta-analyses”
To which, some of use would say, this was all predictable when the EBM bandwagon jumped on the idea that collating some information, and ignoring other information was ‘novel’. Science advances by creating and testing coherent theories of how the world works. Adding together ‘treatment effects’ is messier, and more prone to error. Just because you can enter data in a spreadsheet, doesn’t mean you should.
UCAS has just released its data on medical school applications for this year (2017 entry)……A few bits of background information are useful first. Total applications in 2015 were 82,034 for 7,424 places, which leads to the oft-cited ‘one place for eleven applicants’. However these numbers include multiple applications by students. The number of individual applicants was 20,100 and success at gaining a place depended on country of origin. Success rates were 40% for UK applicants, 10% for EU applicants and 20% for non-EU applicants.
Andrew Goddard, here. I am surprise that the acceptance rate is this high, but I guess there is a lot of self-selection. I do not have a good feel for what is influencing career choices, but the baby boomers had it better — once they got in, sadly. I will stick with my default opinion and change as the evidence changes: what happened to teaching, will happen to medicine. Politics is a dominant negative mutation, and all buckle before it.
This (‘Meaning and the Nature of Physicians’ Work’, NEJM 275;19:1813-5) is one of the best things I have read in a long time. It is right on some big issues, and is only depressing if you think positive action is not possible. The article speaks to the dehumanisation of the practice of medicine, and what happens when there is a gulf between those who practice, and those who think that a summary of practice is the same as actual practice. Tacit knowledge doesn’t fill cells in Excel spreadsheets. It is of course, not just medicine that is changing this way, but other professions — look at what has happened to schoolteaching and the bogus politics and ‘common sense’ that masquerades as evidence in education.
There are lots of downsides to technology making it harder for some things to be forgotten. But lots of advantages too. I use a simple diarying App that is available on mobile and Mac, Day One.
One of its nice features is that gives you the option to see comments you have made on the same date in previous years. Now, like many people I tend to often agree with myself — at least over the short term— but it is fun to read earlier musings and wonder if the nuance needs changing, but also to see the same underlying memes appearing again and again. Often, I am still in agreement, with my earlier comments. Sometimes not. Here is one from three years ago.
On the usually sound principle that there is nothing in UK medicine that can’t be made worse by the involvement of the General Medical Council
Nigel Hawkes in BMJ,10 November 2012
This film from 38 degrees is incredibly moving. And I recognise the places and the hospitals. Worth a critical review, but the abuse of trust is manifest (which is why they are called ‘trusts”). My post title — ‘Forty year ago we would have started a revolution’ — is my favourite line.
The quick retort is, of course, that they are actually treated worse — at least worse than some factory workers. The heading is from an article in BMJ careers. Jane Dacre is quoted as saying we need more juniors, and ‘more boots on the ground’. By contrast, Catherine Calderwood, Scotland’s CMO didn’t agree that an any increase in junior doctors was necessary:
“I’m not sure that more is definitely better. We’ve had a 38% increase in consultants in Scotland in the past eight years, and almost a doubling of our emergency medicine consultants, and I’m not sure if I walked into an emergency department they would tell me it’s half as much work as it was eight years ago.”
She went on to spread the kool-aid a little more:
“I think sometimes doctors have not embraced others doing some tasks, and I would like us to be much more like a conductor for the orchestra. So (only) the really difficult stuff, the really responsible stuff, and the really clever stuff is what comes to the doctor as the senior leader.”
I think some of what they both say is correct, but I also fear some of what they both say is politics. The UK — including Scotland — is desperately short of doctors. Appointment times are too brief, waiting times out of control, clinical expertise increasingly patchy, and doubts about the adequacy of training, widespread. Demand is rising, and wants and needs increasingly confused. From where I stand, clinical service in some areas is getting worse. Scotland’s NHS is, in some parts, second world standard, as a colleague from mainland Europe once reminded me.
The issue about paramedical staff is important, but we have been here before. I may be misquoting the figures a little — and they are for the US— but around 1900 one in three health care workers was a doctor. Now the figure is around 1 in 14. This trend in the ratio will and should continue. The discussions about physician assistants and the like have been going on for over half a century, with little evidence of action. The key issue is that if you want to encourage people to move into new roles, you have to create a certification system that rewards and encourages people to do these jobs. That is why we have radiographers, pharmacists and the like. But successive UK government officials hate the idea of certification, and prefer that ‘nurses’ moves into roles that they have little formal training for, and instead, end up existing free of any meaningful regulation. Governments cannot face up to the fact that these ‘health care workers’ (apologies: an awful bloody phrase) will need more than subsistence wages, and setting the system up will require upfront funding. I used to laugh at the image of a doctor’s office with all the certificates on the wall behind the desk, but now I advise patients always to ask whether the person providing diagnostic or therapeutic activities has a recognised medical qualification. How many melanomas do you diagnose a year?; how many times have you performed this procedure?; what exams did you have to pass etc.
If you ask whether you can train graduates to become physician assistants in dermatology, dermatological surgery and the like, the answer is a clear yes. But to make this a sensible career choice, we need certification — theory and practical exams and so on — and job titles that are transferable wherever somebody works. At present we simply to not have this. The dentists have done this and — key to any debate — practitioners (hygienists etc), whether they are dentists or not are registered with the General Dental Council. Now, the GDC is not a very popular organisation, but the idea of formal certification —something that means that practitioners can move jobs easily — is a key component of making this system work. Institutions matter, as do incentives.