Does drug development deliver on its promises?
pharmafile | October 24, 2011 | Feature | Business Services, Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing | Les Rose, R&D
I am always guided by the motto of the Royal Society, ‘Nullius in Verba’. This means, with typical Latin brevity: “There is nothing in the word”. It is a warning to anyone who might be taken in with well-polished language but little substance, when what really matters is the evidence.
So what is the evidence that drug development really is working?
But what do I mean by ‘working’? Distil the mission statements of 100 companies and we might end up with a small number of objectives. For the community, the first objective must be to produce new medicines in response to unmet medical need. Because people still become ill, and for many illnesses there are no effective treatments, there remains rather a lot of scope here for the drug developers.
Indeed, can we envisage a day when we have fully met the target, and nobody ever has to suffer illness? That seems unlikely. But however we approach it, there will be problems and conflicts, which I’ll come back to shortly.
Once we have identified a way of meeting a medical need, we create the obligation to satisfy that need as quickly as possible. This is one of the most pressing concerns of the industry, and not only for altruistic reasons. We don’t seem to be doing very well at this, with drug development typically taking 8-10 years – a duration that has stayed almost the same for the last decade.
The profit motive
A third objective – to produce value for shareholders – is also essential of course.
Companies are reticent to highlight this, but we have to accept that drug companies are not charities, and profit is the main motivator.
I don’t have the slightest problem with the profit principle, especially when there is very good evidence that society is much better off when people are free to trade. This doesn’t eliminate scope for altruism in companies, and we are seeing some quite creative programmes for delivering affordable drugs to disadvantaged communities.
Bearing these quite traditional aims in mind, let’s look at how some of the top companies see themselves. GlaxoSmithKline says it exists “to improve the quality of human life by enabling people to do more, feel better and live longer”.
This is quite a perceptive and challenging statement, as it contains measurable targets. Not only does it embrace quality of life, but it defines what that is in terms of function and contentment. Bristol-Myers Squibb follows a rather more classical mission:
“To discover, develop and deliver innovative medicines that help patients prevail over serious diseases”. Nothing very quantitative there, and again not a word about grubby commerce. Pfizer’s website doesn’t really have a mission statement as such (at least I could not find it, which speaks for itself), but there are these ‘commitments’:
It pledges to:
• Advance wellness, prevention, treatments, and cures
• Bring the best scientific minds together to challenge the most feared diseases of our time
• Set the standard for quality, safety, and value of medicines.
Fine, but again how will achievement be measured? Of these three, GSK hits the spot because of the focus on outcomes, and particularly on outcomes that matter to people.
I am rather disappointed with Pfizer. For example, setting a standard for quality etc. is not the same as achieving it. So with outcomes in mind, what can we say about how medicines are serving the community?
The pharma industry is the perennial target for conspiracy theorists and the large community of anti-science activists. I have heard these people assert that drugs are ineffective and poisonous, and are only marketed because of an unholy alliance between drug companies and regulators. What is the truth? In reality there is a very large peer-reviewed literature which shows a clear net benefit to society from drug treatment.
Now, while I liked GSK’s mission statement, what do healthcare providers really care about? Do they care about quality of life per se, or are they interested in something else? If they only cared about quality of life, the UK government (which pays for healthcare out of our taxes) would never have established NICE. No, the truth is that cost-effectiveness is what really matters.
The difficulty with this is measuring cost. I have seen lots of health economics studies which only measured direct costs. These are usually defined as costs which are borne solely by the patient being treated, and include loss of working time (for example) as well as the cost of treatment.
Yet society is very well informed on the greater costs of ill-health to the community.
We know that the British economy loses 1-2% of gross domestic product because of muscoloskeletal disorders – a massive figure. The total annual economic cost of diabetes in the US in 1997 was estimated to be $98 billion – $44.1 billion in direct medical and treatment costs, and $54 billion for indirect costs attributed to disability and mortality (quoted from The Wellcome Trust website).
For both these diseases, drugs have a role, although lifestyle changes are also essential. For low back pain, analgesics enable the real treatment, exercise, to be applied more readily, while for diabetes weight reduction complements insulin and anti-diabetic drugs.
Let me give you examples of just how good drugs can be. Firstly, osteoporosis.
According to Patrick and colleagues, writing in the Journal of Clinical Endocrinology and Metabolism: “A one-time cost of $250 and reducing bisphosphonate discontinuation by 30% had an incremental cost-effectiveness ratio (ICER) of $29,571 per quality-adjusted life year in 65-year-old women initiating bisphosphonates”.
In other words, if you can get more women to take their prescribed drugs, you either improve quality of life for the same cost, or you reduce cost for the same quality of life. Well I have to confess that I cheated a bit – these results come from a computer simulation, using data mined from the published literature. What happens in a real life situation?
Menéndez and colleagues studied 271 patients with community-acquired pneumonia, and reported in the European Respiratory Journal that patients who were compliant with published guidelines for antimicrobial use, each cost €1,121 less to cure than those who were non-compliant. This study of course took into account all the costs of treatment, not just the drugs used.
Not surprising you might say, we all know that you have to finish a course of antibiotics. Perhaps not quite so obvious would be another finding of substantial cost savings, this time in mental health. Patients with bipolar disorder had fewer in-patient episodes and hence lower costs when they were compliant with drug treatment, reported Hong and colleagues, in the journal Psychiatry Research.
These are one-off pharmacoeconomic studies, but can they be translated into large-scale benefits? I think so, as was shown by the Asheville project. This city in North Carolina, US, ran a major study in which pharmacists were paid to spend time with patients, explaining their treatment and monitoring compliance.
The main outcome was quite astonishing – insurance claims fell by 70% over five years, and total cost of disease by 30%. One important aspect of the study was that co-payments were largely stopped. The effect was that, when patients were paying virtually the full cost, they valued the treatment more, complied at up to 95% (instead of typically 50%), and total healthcare costs took a dive. Would this happen if the drugs were not working?
These are just a few examples from a substantial literature on the economic benefits to society of drug treatment. Where the process falls down is in getting these valuable treatments out into the field quickly. Data from industry tracking specialists such as CMR International show that, whereas there have been significant changes in certain cycle times in the clinical development pathway, overall new drugs are not reaching the market any faster that a decade ago. This is despite massive changes in technologies such as electronic data capture. What can be going wrong?
Whatever is the cause, we owe it to society to redress the balance. We need to be as good at speed of development as we are at innovation. And we are good at innovation – there are over 600 new cancer drug compounds in development today.
So let’s return to the subject of the major companies’ reticence to overtly declare their profit-making goals. Perhaps they take this as a given. The pharmaceuticals business is usually seen as a high-risk/high-return one, but with margins squeezed by pricing and regulatory pressures, risk aversion has been a clear trend over recent years. These companies know that most drugs they launch will not recover their development costs, so what do they do?
They seem to be spreading the risk more evenly by avoiding high-risk innovative candidates, which is a disappointment when we know they can deliver great medicines.
It will probably take decades to sort this out. If companies could be confident about getting to market earlier, they might be prepared to push the envelope a bit more and go for the tougher medical targets. So if there is a component of drug development that isn’t working optimally, it surely is time-planning and management. That will no doubt need some radical remodelling of the way we do it.
Les Rose is a freelance clinical scientist and medical writer.
www.pharmavision-consulting.co.uk
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