Coping with Uncertainty in Primary Care

People tend to like certainty in their lives with risk and insecurity excluded. They expect professional people, especially doctors, to give firm and unequivocal answers to their questions. "Nothing in life is certain except death and taxes" wrote Benjamin Franklin, but he was a scientist.

Coping with uncertainty offers two problems for healthcare professionals. One is coping with our own uncertainty. The other is explaining uncertainty and the nature of risk and risk management to others. Life is about balancing risks. We must explain to our patients that even the most secure of assertions may possibly be wrong and that being wrong is not necessarily indicative of incompetence or malpractice.

The introduction of evidence-based medicine is something of which the profession can be justly proud. The gold standard of clinical research is the randomised controlled trial, preferably with double blind placebo control. Sometimes the rarity of a condition makes large trials impractical. RCTs may be the gold standard of the burden of proof, but what do they prove?

The best that they can hope to achieve is to demonstrate that there is a low probability that the null hypothesis is true and the intervention is ineffectual. That is not the same as absolute proof that it works. People sometimes say, "You can prove anything with statistics." Quite the opposite is true. It is possible to prove nothing with statistics, only to show that there is a very low likelihood that the observations were a random occurrence.

Very often proof of the efficacy of an intervention is based on a P value around 0.05. This means that even without poor methodology and selective publication, that there is a chance of around 1 in 20 that it is totally useless. Even P<0.001 is not absolute proof. A chance of 1 in 14 million may seem as good as impossible but at least one person usually wins the National Lottery every week.

Meta-analysis is a technique that is often highly rated by reviewers but it is fraught with danger. The trials to be summated must have similar methods for selecting participants and for measuring results. Any incongruity makes the summation meaningless. It is assumed that all are of good methodology but often it is impossible to tell this simply by reading the paper. If there are errors, they are likely to be multiplied.

Perhaps the greatest problem that meta-analysis will compound, is selective publication. For this reason, meta-analysis should really be accompanied by funnel plotting and cut and fill. A classic example occurred when meta-analysis of only the good papers about homeopathy showed that it does really work¹ but a few years later, analysis by funnel plotting with cut and fill showed that selective publication is so marked that, accounting for the unpublished papers that could be assumed, it does not work at all.² Negative results are just as important as positive ones provided that sample size was adequate to have a good chance of showing any significance if it exists.

When faced with a patient we have to ask 3 questions:

• What evidence exists?
• How valid is the evidence?
• How applicable is this to the patient in front of me?

There is a great deal of high quality evidence about the management of heart failure but for good methodological reasons the subjects have been aged around 55 with ischaemic heart disease and no other pathology. The typical patient who presents to the GP is, on average 85, has multiple pathologies and is on multiple medication. This is not a reason to reject the evidence as it is the best available. It simply needs to be mixed with some common sense and practicality. Probably 95% or more of depression is treated in primary care yet almost all the literature is written by psychiatrists. We may ask who benefits from antidepressants? The majority of evidence will be based on the most severe 5% who are referred to a psychiatrist.

Screening can be a very effective way of reducing the burden of disease but people who go for screening often expect to be given a firm assurance that they either have or have not the disease. Any screening procedure will have specificity and sensitivity. Specificity relates to the number of false positives, that is people who are recalled for further investigation and subsequently found to be free of disease. Sensitivity relates to false negatives, when people are falsely assured that they are clear. A good screening test should have a high specificity (low rate of false positives) and a very high sensitivity (very low rate of false negatives). No screening system can be without some degree of uncertainty. If the false negatives are 1% this means that of every 100 people screened who had the disease, 99 were detected and this should be a cause for celebration, not recrimination. The problem is where to draw the line of abnormality. Criteria that are too stringent will result in too many false negatives and bring the system into disrepute whilst being too lax will give an unacceptably large number of false positives causing undue anxiety in patients and overburdening the system.

The ability to calculate risk, as with risk for coronary heart disease or stroke, can be very valuable but it is essential to explain the results to patients. A bookmaker does not know who will win a race but he knows who probably will win and who is most unlikely to win. Favorites sometimes fall and outsiders sometimes win. There is a tendency to believe that any risk over 50% is an absolute certainty whilst any under 50% is complete safety. No one can see into the future and know who will develop heart disease and who will not. All we can do is to adjust risk factors so as to minimise risk.

A patient with cancer may have been told the 5 years survival for his type of tumour at that stage. A 20% survival is rather a bleak outlook with 4 patients in 5 being dead within 5 years but it is not totally without hope as it also means that 1 person in 5 will make it through and it may be him. Similarly a 90% survival is not a guarantee of cure. It is very encouraging but 1 person in 10 will die. Explain things both ways to give reality but try to look on the optimistic side or hope will perish and the patient soon after.

Nowadays patients help to share in decision making and so they must be taught to comprehend risk.³ If possible use a range of techniques and try to have unbiased visual aids available.^4,5There is an increasing body of evidence supporting the design of effective evidence-based communication tools but there is variable access to such tools in practice.⁶

What is an abnormal result? Many parameters have a Gaussian distribution and often laboratories take arbitrary cut off points such as 2 or 2.5 standard deviations from the mean. If 2 standard deviations is taken as the line then 5% of people will fall outside it with 2.5% above and 2.5% below the range. Hence 1 person in 20 will be abnormal for that parameter and if 20 different parameters are measured, most people will be abnormal for at least one. Nowadays laboratories tend to call it the reference range rather than the range of normal.

If a result is unexpectedly abnormal the first thing to do is to repeat it, especially if it is just outside. Similarly, there may be overlap between the ranges for healthy and pathological, so that a normal result may give false reassurance. It is essential to keep an open mind when interpreting results and to try to avoid classifying everything in terms of absolutes. The interpretation of prostatic specific antigen (PSA) is especially fraught and it is said to be too unreliable as a screening tool for prostatic carcinoma.⁷

Making a diagnosis is a matter of looking at the evidence and drawing a conclusion. There may also be differential diagnoses. Diagnosis is a matter of selecting the most likely option and even a barn door diagnosis may eventually prove to be wrong. In the words of Robert Burns, "There is no such uncertainty as a sure thing". It is essential to keep an open mind to this and, without being unduly fickle, being prepared to consider other possibilities, especially if the situation changes. A degree of self-confidence is important if others are to have confidence in you but a degree of self-questioning is also required.

Many people would be horrified to learn that 20 to 30% of all appendices that are removed for a diagnosis of acute appendicitis, are completely normal. The surgeon who removes more than 80% abnormal specimens is probably not removing enough and is waiting too long to intervene. Acute appendicitis and myocardial infarction are common diagnoses but not easy diagnoses. Admission to hospital with this, and with many other conditions, especially in children, is based on the premise that there is sufficient risk of a serious diagnosis that admission is indicated. Especially in primary care, it is a matter of screening. Do not be embarrassed that sometimes your patients are admitted, observed and discharged. The question is where to draw the line. If you are too rigid in your criteria you will fail to admit a significant number with serious illness but if you are too lax you will overburden the emergency system with unnecessary cases. Careful history and examination can aid discrimination but it will not provide absolute certainty.

There are many claims for herbal or "natural" remedies that are 100% effective and without side-effects. There is no therapy that is completely safe and entirely effective. Which was the largest island in the world before Australia was discovered? The answer, of course, is Australia. Just because no one knew about it did not mean that it was not there. So too, adverse effects of treatments cannot be assumed to be absent because no one has looked for them.

You are faced with an elderly patient with osteoarthritis. Do you prescribe an NSAID, a COX-2 inhibitor, a codeine-based or related drug, plain paracetamol or nothing and how do you justify your decision? When faced with a patient at high risk of arterial disease the benefit of low dose aspirin is such that it greatly outweighs risks. For a patient at low risk of arterial disease this may not be so. The younger patient is at lower risk of adverse effects but so very much lower is the chance of benefits that risks do not match benefit.

We often hear of new "wonder drugs" that patients believe they must have to save their lives. No one can be sure that a certain therapy will alter their outcome unless it changes the result from 0% to 100%. Imagine that a new drug for cancer has been subjected to a vigorous trial in which 1,000 patients received the current therapy and 1,000 the new treatment. During the course of the trial 60 patients in the group receiving standard therapy died as did 40 in the trial group. Which of the following statements is true?

• The death rate fell from 6% to 4%
• The death rate fell by 2 percentage points
• The new treatment can prevent a third of deaths
• It is necessary to treat 50 patients with the new treatment to save 1 life
• The benefits may not be sustained with longer follow up

All these statements are true but it is the one about dropping the death rate by a third that will be publicized. Spin is not limited to cricket and politics. As Benjamin Disraeli once put it, "There are lies, damned lies and statistics."

Decisions are based not just on the level of risk, but on the potential outcome. Would you be prepared to walk along a beam 10cm wide and 1 metre above the ground? Would you walk along that same beam if it were 3 metres above the ground or 30 metres above the ground? Would you walk along that beam 30 metres above the ground if it were the only way to escape a fire? The risk of falling is the same each time. It is the outcome of falling and the benefit of crossing the beam that varies. Thus a 10% risk of a rash whilst taking a life saving drug is acceptable but a 10% risk of a serious adverse effect when treating a minor illness is not.

The fact that 20% of parents nationwide and 30% of parents in London do not let their children have the MMR vaccine is testament to an abysmal failure to communicate. The BBC and ITV still insist on referring to it as the controversial MMR vaccine and pretend that expert opinion is evenly divided. Experts often mar their testament by expressing a degree of uncertainty that is appropriate for the scientific community but which undermines the message to a lay audience. To say, "All the evidence points to the vaccine being safe and there is absolutely nothing to link it with autism or bowel disease," is correct and decisive. Autism often becomes apparent about the age of vaccination but association and causation are not the same. Retrospective analysis has often showed that there was some evidence of regression before the injection.
If parents are indecisive or antagonistic, present them with the following facts:

• The original paper linking the MMR vaccine with autism and inflammatory bowel disease⁸ has been retracted by all its authors except one and the editor of The Lancet says that he would never have published it if he had known that it was such bad science.
• This flawed paper was based on 12 children. A study from Denmark, based on over 537,000 children⁹ found no association between the vaccine and autism.
• Many others, both in the UK and throughout the world have looked to see if there is an association between the MMR vaccine and autism and none has been found.
• The incidence of autism started to rise around 1980 but the MMR vaccine was not introduced until 1987. Within 18 months the uptake was over 90% but this had no effect on the rate of rise in autism.
• No country is the world has been sufficiently concerned as to withdraw the vaccine because of safety.
• Japan had problems with production of MMR vaccine and so had to revert to separate injections for a number of years since when they have re-introduced it. None of this has affected the incidence of autism in Japan.¹⁰
• The editors of journals like the BMJ and The Lancet, the Royal Colleges and academics throughout the country and throughout the world are very independent people and there is no dissenting voice.

In conclusion, the risks of being unprotected against the diseases far outweigh any risks associated with the vaccine. Still parents may ask for separate vaccines. The arguments against this are listed in health promotion for young children. A paper from Bandolier is recommended.¹¹

An essential part of clinical governance is the management of risk. No one can fail to be impressed by what nurses have achieved by protocol driven care. Doctors tend to reject protocols as painting by numbers but much of what doctors do in terms of history and examination is a protocol, even if it is subconscious. Protocols represent best practice. Without them it is variable practice. Things do sometimes go wrong and if a doctor is called to account for his actions and asked, "Why did you do it that way?" and he replies, "That is our protocol," he is on strong ground but if the best he can offer is, "It seemed a good idea at the time," he will be much less comfortable. Protocols do not prevent clinical freedom but deviation from them must be justified.

Critical event monitoring was introduced to the RAF in the Second World War by a psychologist called Flanagan. It has been taken up by the National Patient Safety Agency.¹² An adverse event is when things go wrong. A critical event is when things may have gone wrong. It is important that they are discussed openly as an opportunity to learn and not as a disciplinary matter. Critical events outnumber adverse events many-fold. It is important to ask if education needs to be offered or care pathways changed to prevent repetition and possibly disaster. Particularly with the changing face of clinical responsibility it is essential to assure that knowledge and skills match demands. Skills for Health¹³ are able to offer support and advice.

No matter how carefully you practice, adverse events will occur. The risk can be minimised but not eliminated. This is why everyone needs personal indemnity insurance. It is sobering to think that despite advances in risk management, the annual subscription to the MPS or MDU in 1974 was £25. We have had a great deal of inflation since then but not enough to account for a figure over 100 times the size.

Around 1850 it was thought that science had advanced so far that before long everything that was to be known would be known. Yet in the 4th century BC Aristotle had written a philosophy that may be summarized as "The more you know, the more you know you don't know". Uncertainty is wisdom, not foolishness. Mark Twain wrote, "Education is the path from cocky ignorance to miserable uncertainty."

Not just medical practice but all of life is about uncertainty. The rehabilitation of offenders should aim to balance the risk an individual may pose to society against the desirability of making that individual an integrated member of society. A rail crash in which 10 people are killed raises a public outcry whilst, on average, nearly that number is killed on the roads every day. Forensic psychiatrists will always be criticized if they declare a patient to be safe, he is released and does harm. Yet who will criticize a forensic psychiatrist who would incarcerate all his patients for ever? People should not look simply at the occasions when things go wrong but at the many more times when they go right. Compare benefits and risks.

Francis Bacon wrote, "If a man will begin with certainties, he will end in doubts; but if he will be content to begin with doubts he will end in certainties." All our world, not least the NHS, is beset by constant change and that means uncertainty. Uncertainty is wisdom. Dogma is weakness. We must learn to love uncertainty.

The following have been confirmed from the Oxford Book of Quotations:

• Nothing is certain in life except death and taxes. Letter from Benjamin Franklin to Jean Baptiste, 13th November 1789, recorded in The works of Benjamin Franklin.
• Mark Twain attributed the quotation to Benjamin Disraeli in his autobiography of 1924. There are three kinds of lies: lies, damned lies and statistics.
• If a man begin with certainties, he will end in doubt; but if he will be content to begin with doubts, he will end in certainties. Francis Bacon. The advancement of learning 1605.

The following are from the Internet and hence of more dubious authenticity. The quotation is followed by the years in which the individual lived.

• Robert Burns: There is no such uncertainty as a sure thing. 1759 to 1796.
• Mark Twain: Education is the path from cocky ignorance to miserable uncertainty. 1835 to 1910.