In clinical practice we are encouraged (often stridently) to pursue evidence based strategies in the management of our patients and clients. This it is claimed is to provide us with the best outcomes and minimise risk – suggesting that the role of the individual clinician should be confined to Data sets and then squeezing the patient to fit this model.
Many patients (annoying reality vs. statistical averages) present with co-morbidities – more than one significant complaint especially in primary care practice. Yet most RCT’s exclude patients such as these from their trials, or they are not reported as such in the completed data. Most patients in primary care practices have multiple comorbidities. In fact, in one representative population of nearly 1000 patients, 90% had more than one chronic condition; among those older than 65 years, almost all had 2 or more disorders. Others are by their generalised nature prone to leaving out the young, the elderly and ethnic minorities.
Yet the data sets are selected to confer treatment outcomes for all, the bell shaped curve of benefit means that outliers will not respond and only those that meet the studies input and output targets will do so. This I suggest, means that a significant number of the patients presenting are faced with receiving a simplified and potentially inadequate protocol driven treatment. In effect the square peg is driven by the RCT to fit the round hole.
It is an unfortunate fact that medicines are currently not as effective as they could be in an average of around 50% of patients, and in certain indications the success rate is even lower.[1]
For many of the most lucrative drugs, the benefits of treatment are of an order of magnitude less than this. For example, less than five per cent of patients receiving long-term treatment with statins are likely to obtain any benefit whatsoever. Put another way, of every one million pounds spent on lipid-lowering agents, more than £950,000 is wasted. Consider the evidence collected from a number of studies on the benefits that people gain from the use of statins for 5 years.
Statin Drugs Given for 5 Years for Heart Disease Prevention (Without Known Heart Disease)
|
|
|
|
|
In other words
|
|
|
|
Statins Given for 5 Years for Heart Disease Prevention (With Known Heart Disease) [2],[3],[4]
|
|
|
|
|
In other words
|
|
|
|
“What if you put 250 people in a room and told them they would each pay £750 a year for a drug they would have to take every day, that many would get diarrhoea and muscle pain, and that 249 would have no benefit? And that they could do just as well by exercising? How many would take that?
An estimated 10% to 15% of statin users suffer side effects, including muscle pain, cognitive impairments, and sexual dysfunction. And the widespread use of statins comes at the cost of millions of pounds a year, not just for the drugs but also for doctors’ visits, cholesterol screening, and other tests. The NHS bill for statins in 2004 came to £769m.
A recent Cochrane review on statins from 14 trials involving 34 272 patients threw further doubt on the role of medicalising what is in effect a lifestyle induced disease[5],[6] ,[7]– the lead author of one paper, Dr Shah Ebrahim stated:
“If you look at the hard end points of all deaths and coronary deaths, the effects are consistent with both benefit and with the play of chance. But importantly, the absolute benefits are really rather small—1000 people have to be treated for one year to prevent one death. It is probably a real effect, but it means a lot of people have to be treated to gain this small benefit. As we don’t know the harms, it seems wrong-minded to me to treat everyone with a statin. In these circumstances, lifestyle changes and stopping smoking would be far preferable.”
Decision Making
Our brains devote a great deal of time and space to processing information about other people — about what they think, know, want and intend. Because we specialise in understanding other minds, we are hypersensitive to the harms those minds produce. We worry more about our children being kidnapped by strangers than about becoming obese, despite the fact that abduction is rare and diabetes is not. Terrorists and child-molesters are agents, viruses and French fries are objects, and agents threaten us in a way that objects never can.
Human’s sociality has always been a great advantage, but it may also be its undoing. Because we see the world through a lens of friends and enemies, heroes and villains, alliances and betrayals, virtue and vice, credit and blame, we become riveted by the dramas that matter least and apathetic to the dangers that matter most. We will change our lives to save a child but not our energy consumption to save them all.
This even translates into health care. If we are not careful we become fixated on the statistical evidence, despite the need to see each person as an individual. Protocols become the tool of intervention and are often used despite the absence of beneficial outcome or development of side effects. Emergency medicine mostly works because of standard protocol driven interventions – albeit that there are exceptions. Primary care of complex lifestyle driven illness works less well as a protocol EBM interventionist’s playground. Here listening and learning from patients and clients may require different strategic interventions and recommendations.
Value of positive and negative anecdotes in clinical life
The gold standard of evidence as described is RCT also referred to as level 1 evidence and the least attractive to advocates of the ‘RCT or nothing genre’ is anecdote – the personal experience – yet I suspect that this is the very type of evidence that all clinicians are driven by. Let’s refer to this evidence delivery system as level 4, Level 2 is observational studies and Level 3 is expert opinion. Once in practice it soon becomes apparent that real life events make a nasty habit of jumping in and disturbing odds ratios, both adverse and positive experiences start to shape strategies and recommendations.
The instinct that drives us to act on the basis of Level IV evidence dates far back into our evolutionary history. Neuroscientists have demonstrated that strong emotions modulate learning and memory.[8]
The result is that both adverse and beneficial personal experiences are not simply better retained than the memories generated by reading a Cochrane review, but they are also more compelling. Whilst RCT’s may take many years to be translated from journals to clinical life, emotive experiences can change decision making almost instantly. Fighting this historically engraved midbrain feature is virtually impossible and to a large extent continues to explain that whilst anecdotes do not make data – they still have powerful and significant decision making influence.
If we can combine informed adverse and positive anecdote with scattered data sources, the outcome will be sound clinical judgment and better clinical outcomes. This of course is what personalised medicine is all about, the information required being dragged from numerous sources and placed in context along with shared engagement and treatment.
Comment
Functional and integrative medicine take this concept as a key part of their approach to clinical life and relevant decisions, regrettably proponents of RCT driven decision making tend to regard these aspects as little more than statistical noise with no place in health care. I am not convinced of the ability or benefit of practitioners doing so.
For those of you interested in listening to an illuminating lecture presented by Prof Michael Rawlings, you may enjoy listening to his Harevian Oration titled “De testimonio: On the evidence for decisions about the use of therapeutic interventions” at the Royal College of Physicians in 2008.[9] If you prefer a written format you may find a PDF link in theReference section.[10]
Rawlins shows that the randomised controlled trial (RCT) is not the “be-all and end-all” of evidence in medicine. He shows that the hierarchical grading of levels of evidence (RCTs at the top with case reports at the bottom) is overly simplistic and irrational. He advocates using case-by-case judgement to assess the value of a given study:
‘Such judgements relate to – the extent to whether each component of the evidence base is “fit-for-purpose”. Is it reliable? Is it likely to be generalisable? Do the benefits outweigh the harms?’
It may be useful to reflect that Austin Bradford Hill, the architect of the RCT has stated:
‘Any belief that the controlled trial is the only way would mean not that the pendulum had swung too far but that it had come right off the hook’
References
[1] Severin Sachwan, CEO, Roche (Burrill & Co Biotech 2009 – Life Science: Navigating the Sea Change)
[2] Thavendiranathan P. Primary prevention of cardiovascular disease with statin therapy. Arch Int Med. 2006; 166: 2307-13. View Abstract
[3] CTT Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet. 2005; 366: 1267-1278. View Abstract
[4] Ridker et al. Rosuvastatin to prevent vascular events in men and women with elevated c-reactive protein. NEJM. 2008; 359(21): 2195-2207. View Abstract
[5] Taylor F, Ward K, Moore THM, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2011; 1 (CD004816). View Abstract
[6] Ebrahim S, Taylor F, Ward K et al. Multiple risk factor interventions for primary prevention of coronary heart disease. Cochrane Database Syst Rev 2011; 1 (CD001561). View Abstract
[7] Heneghan C. Considerable uncertainty remains in the evidence for primary prevention of cardiovascular disease [editorial]. Cochrane Libr 2011 (January 19, 2011). View Abstract
[8] LaBar KS, Cabeza R. Cognitive neuroscience of emotional memory. Nat Rev Neurosci 2006;7:54-64. View Full Paper
