Lets play the word association game.
Health.
Disease.
Drugs.
In our society pharmaceutical products are the first port of call when we feel unwell. The existence of a pill-popping culture is something that science writer Ben Goldacre makes a particularly good case for in his bestseller, Bad Science. The BBC Horizon programme "Defeating the Superbugs" revealed that in India it is possible to buy antibiotics from what is the equivalent of corner shops. As you may have done with your penny sweets people can buy as much treatment as they can afford or want rather than a prescribed course. Whether it is a culmination of misinformation and lack of education about antibiotics or purely sheer idiocy, this throws into question the responsibility we all have when it comes to drugs. This story is particularly relevant in light of recent news that the Chief Medical Officer for England is drawing parallels between antibiotic resistance and terrorism in terms of the threats they pose. Here is a link to the BBC article in case you missed it.
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| Pick N Mix antibiotics anyone? (This work is licensed under a Creative Commons Attribution 3.0 Unported License.) |
You probably take various drugs every year; whether it is aspirin after a long night or something more serious, pharmaceutical compounds are something everyone has experience of. But how many people know the process by which they are approved?
How much do you know about: Clinical Trials.
A lot has changed.
Drug development has been around in some shape or form for hundreds of years but, as you can probably imagine, a lot has changed. Most noticeably the scale of development has grown enormously; 200 years ago most drugs would be prepared by individuals using natural resources and there were very limited amounts, now the World Heath Organisation (WHO) estimates the global pharmaceutical industry to be worth $300 billion a year. Obviously with such presence a comes lots of control and standardization - particularly when it comes to the discovery and eventually approval of use for a new drug.
So, how is the medical research carried out in humans?
Each phase has its own unique aim.
Phase 1. - find the maximum tolerated dose and schedule of administration. The new drug is first tried at a very low dose in three people and gradually increased, each time administered to another three people, until side effects emerge in two out of three of the subjects - it is at that point the maximum dose is defined.
Phase 2. - assess the effectiveness. Characteristic of clinical trials is the increase in the number of patients at each phase - during the second phase the number increases from around 20 to over 100.
Phase 3. - compare it against the current best treatment. If it isn't any better then there is no point in continuing. But, better doesn't just have to mean it is a more effective than the current drug, it could be the same effectiveness but with fewer side-effects - the drug will still have a big impact on a patient's quality of life. The number of patients in this phase reaches the thousands.
If a drug makes it past this phase it gets licensed which may seem odd as the trial hasn't officially ended. But, it has been deemed safe enough and its effects impressive enough to be tried on the general population.
Phase 4. - watch how it is getting on.
So those were the basics of a the human part of clinical research, as I was taught them in my biochemistry degree! But - there was something even more interesting I hit upon when reading around about clinical trials..
The Placebo Effect.
This is a widely studied phenomenon but one man I particularly started reading about was Ted Kaptchuk. According to the biography on his website Ted originally studied Chinese medicine and is now a prominent figure in the "Placebo community" having had numerous scientific publications.
One publication in the British Medical Journal (BMJ), a highly esteemed journal where researchers and professionals can specifically find information and studies about health, caught my eye - a summary can be found here. It caught my eye because it showed how the scientists view on placebos is changing. If you Google "clinical trials with placebo" a whole host of articles boasting of "placebo-controlled studies" will appear - placebo's often form an integral part of a trial. But, what Kaptchuk's 2012 study showed was that in the 19th Century placebos were not regarded with as much significance.
How was the study conducted? The researchers simply searched a computer database for any papers containing the word "placebo" in the archives of the BMJ between 1840 and 1899. Bit like pressing Ctrl "F" when looking something up on your laptop really. But this has a more technical name than the Ctrl "F" trick, this study is a Meta-Analysis. It may seem surprising but meta-analyses are one of the highest regarded forms of scientific research: you combine all the previous research that match the criteria you set, in this case containing "placebo", and draw conclusions from looking at all of the results. What they found was that nearly a third of all papers published at this time described placebos in a derogatory way, or used the term interchangeably with "no effect". Only one paper out of the 71 assessed suggested the placebo had "a clinical effect".
Debate about the "Placebo Effect" is now much more prominent than this study suggests it was in the 1800s.
If you are interested you might enjoy this video on the NHS website where Ben Goldacre discusses the placebo effect, he also brings in the ethical issues surrounding "lying" to patients who are actually receiving placebos.
A lot has changed.
Drug development has been around in some shape or form for hundreds of years but, as you can probably imagine, a lot has changed. Most noticeably the scale of development has grown enormously; 200 years ago most drugs would be prepared by individuals using natural resources and there were very limited amounts, now the World Heath Organisation (WHO) estimates the global pharmaceutical industry to be worth $300 billion a year. Obviously with such presence a comes lots of control and standardization - particularly when it comes to the discovery and eventually approval of use for a new drug.
So, how is the medical research carried out in humans?
Each phase has its own unique aim.
Phase 1. - find the maximum tolerated dose and schedule of administration. The new drug is first tried at a very low dose in three people and gradually increased, each time administered to another three people, until side effects emerge in two out of three of the subjects - it is at that point the maximum dose is defined.
Phase 2. - assess the effectiveness. Characteristic of clinical trials is the increase in the number of patients at each phase - during the second phase the number increases from around 20 to over 100.
Phase 3. - compare it against the current best treatment. If it isn't any better then there is no point in continuing. But, better doesn't just have to mean it is a more effective than the current drug, it could be the same effectiveness but with fewer side-effects - the drug will still have a big impact on a patient's quality of life. The number of patients in this phase reaches the thousands.
If a drug makes it past this phase it gets licensed which may seem odd as the trial hasn't officially ended. But, it has been deemed safe enough and its effects impressive enough to be tried on the general population.
Phase 4. - watch how it is getting on.
So those were the basics of a the human part of clinical research, as I was taught them in my biochemistry degree! But - there was something even more interesting I hit upon when reading around about clinical trials..
The Placebo Effect.
This is a widely studied phenomenon but one man I particularly started reading about was Ted Kaptchuk. According to the biography on his website Ted originally studied Chinese medicine and is now a prominent figure in the "Placebo community" having had numerous scientific publications.
One publication in the British Medical Journal (BMJ), a highly esteemed journal where researchers and professionals can specifically find information and studies about health, caught my eye - a summary can be found here. It caught my eye because it showed how the scientists view on placebos is changing. If you Google "clinical trials with placebo" a whole host of articles boasting of "placebo-controlled studies" will appear - placebo's often form an integral part of a trial. But, what Kaptchuk's 2012 study showed was that in the 19th Century placebos were not regarded with as much significance.
How was the study conducted? The researchers simply searched a computer database for any papers containing the word "placebo" in the archives of the BMJ between 1840 and 1899. Bit like pressing Ctrl "F" when looking something up on your laptop really. But this has a more technical name than the Ctrl "F" trick, this study is a Meta-Analysis. It may seem surprising but meta-analyses are one of the highest regarded forms of scientific research: you combine all the previous research that match the criteria you set, in this case containing "placebo", and draw conclusions from looking at all of the results. What they found was that nearly a third of all papers published at this time described placebos in a derogatory way, or used the term interchangeably with "no effect". Only one paper out of the 71 assessed suggested the placebo had "a clinical effect".
Debate about the "Placebo Effect" is now much more prominent than this study suggests it was in the 1800s.
If you are interested you might enjoy this video on the NHS website where Ben Goldacre discusses the placebo effect, he also brings in the ethical issues surrounding "lying" to patients who are actually receiving placebos.
Now that placebos are viewed with a slightly more positive spin, what sort of clinical effect have they been shown to have? If so, does the effect vary with how the patient sees them (like if they're administered by needles they might seem more important than pills) or not?
ReplyDeleteI think a better way of putting it is that are being taken more seriously. And it doesn't seem to just be a psychological thing, as in its easy to see how we might feel less pain when we think we are getting drugs as pain can be associated with your mind..but how can we explain physical changes that happen as a result of the placebo effect? In the video I posted a link to Ben Goldacre describes how gastric ulcers get better as a result of sugar pills! He also talks about how the colour of the pill affects results, as well as if the placebo is an injection or tablet - so it seems like the effect does vary with how the patient sees them.
ReplyDelete