Randomised controlled trials and meta-analyses usually give us the “best” estimate of the effect of a treatment.
However, applying these results to an individual person requires clinical judgement. This may take into account many factors, including:
How will benefits and harms play out over time?
Trial data shows us what happens over a limited period, sometimes less than 1 year. The absolute risk reduction shown over these short time periods may be very small, perhaps just 1-2%.
But absolute benefits are likely to add up over time. So, for example, a treatment with a trial result showing a 1% absolute risk reduction in a 1 year period might give a 5% absolute risk reduction over 5 years.
However, there is mostly no scientific proof that this increase in benefit will be the case. Some treatments may have their biggest impact over the short term. For example:
It is also important to think about the prognosis of a condition without treatment. For example heart failure with reduced ejection fraction (HF-REF) deteriorates over time if untreated, so the effects of treatment need to be considered against that alternative scenario.
Over the much longer term (say, more than 10 years), things are even more uncertain. For example:
This seems unlikely. This sort of calculation suggests risk can be reduced to zero with enough time.
There are also what are known as “competing risks”. People develop other illnesses and die from other causes, so they do not benefit from the theoretical risk reduction of the treatment being considered.
Is my patient like the patients in the clinical trials?
If the trial participants were mostly White, North American males aged 60 with a single condition and the research was conducted in the 1980s … can I apply those results to a patient with very different characteristics today?
Again, there is little hard science to guide us (and if there was, it would probably be condition and treatment specific).
As a rule of thumb, it may be best to think more in terms of physiology and baseline risk rather than demographics.
Physiological differences: co-morbidities and metabolic impairment, frailty, polypharmacy will all affect the benefit-risk ratio of a treatment, particularly risk of treatment harms.
Baseline risk: results from clinical trials conducted in particular high-risk groups are sometimes extrapolated in clinical guidelines to apply to people at lower baseline risk. This means that a lower-risk person is less likely to benefit from treatment than the trial population. Where this is a particular issue, we have highlighted it on this website.
Very old age and the presence of life-limiting illness: “competing risks” become key. How likely is it that this person will live long enough to benefit from preventive treatment? How likely are they to die from another condition or old age? Will treatment side effects cause suffering in the time they have left?
Differences in sex, ethnicity, age and geography are probably less important. Unless there is evidence or a good physiological reason to think different demographic groups will respond differently to a treatment, it is probably best to assume that benefits apply to all. The risk of denying effective treatment to someone because their demographics differ from a trial population is probably greater than a theoretical risk from applying evidence from another demographic group to the person in front of you.
Trials underestimate treatment harms
Clinical trials tend to recruit healthier people in middle and early old age, exclude people at high risk of treatment harms, and provide high quality follow up to minimise treatment risk.
This may mean your patient is more likely to experience harms than the trial participants were. Unfortunately there is no formula for estimating the risks to an individual based on trial data.
However, looking at the demographics and biological parameters of the study population can give you a guide as to “how different” your patient is from the average in the trials, and how much more at risk they might be from treatment harms.
This website is designed for use by General Practitioners and other healthcare professionals. The content is not exhaustive and assumes a standard level of GP professional knowledge. The information here is intended to support clinical judgement and shared decision making alongside clinical guidelines and standard practice.
If you are a patient/member of the public, do feel free to look around, but please don’t make any changes to your treatments based on information here. If you find something which seems relevant to you, you could show this website to your healthcare professional to help a discussion.