Reviewing medication need and effectiveness

Assessing the need for preventative treatment in patients with shortened life expectancy/frailty

Identifying patients with shortened life expectancy

Good palliative care is not just about supporting someone in their last months, days or hours of their life, but about enhancing the quality of life for both patients and families at every stage of the disease process.

Identifying shortened life expectancy

  • Where ‘no’ is the answer to the question, ‘would you be surprised if this person were to die in the next 6 to 12 months?’
  • Where a patient with advanced disease is making a choice for comfort care rather than curative treatment
  • Where help is required for multiple activities of daily living, either at home or in care home due to:
    • advanced organ failure
    • multiple co-morbidity giving significant impairment in day to day function
    • advanced dementia


The Gold Standards Framework from Living Well/Dying Well provides prognostic indicators to identify those requiring supportive palliative care.  The Supportive and Palliative Care Indicators Tool (SPICT) is an alternative means to identify these patients.

 

Identifying patients with frailty

The Gold Standards Framework also gives specific information as to what tends to indicate poor prognosis in a number of conditions, including frailty.

 

Frailty is well defined as a ‘reduced ability to withstand illness without loss of function’. The Gold Standards Framework defines this further as:

  1. Multiple co-morbidities with signs of impairment in day to day functioning
  2. Combination of at least three of:
    • Weakness
    • Slow walking speed
    • Low physical activity
    • Weight loss
    • Self-reported exhaustion

NICE guidance on identifying frailty can be found here


There are a number of recognised frailty identification tools (e.g. electronic frailty index( eFI) ). Those carrying out medication reviews should use the recommended tool, as chosen by their Board. 

The NHS Scotland Palliative Care Guidelines sets out the consensus opinion on good practice for the management of adults with life limiting illnesses.

 

Understanding numbers needed to treat (NNT)

 

The ‘number needed to treat’ (NNT) is a measure used in assessing the effectiveness of a particular intervention, The NNT is the average number of patients who require to be treated for one to benefit compared with a control in a clinical trial. It can be expressed as the reciprocal of the absolute risk reduction.  The ideal NNT is 1, where everyone improves with treatment: the higher the NNT, the less effective is the treatment in terms of the outcome and timescale described in the trial. So if treatment with a medicine reduces the death rate over five years from 5% to 1% (a very effective treatment), the absolute risk reduction is 4% (5 minus 1), and the NNT is 100/4, i.e. 25.

 

To give an indication of the likely impact of the intervention in the next year, the Drug Efficacy tables that follow illustrate an “annualised NNT”. This assumes that the clinical effect is seen at an even rate over the period of the intervention. So, if the NNT for the medicine to prevent one death in 5 years is 25, the estimate for the annualised NNT, that is, to prevent one death in one year is then 125.

 

In other words, the number needed to treat with that medicine for one year to prevent one death is 25. The ideal NNT is 1 where everyone improves with treatment. The higher the NNT, the less effective is the treatment. There is always a need to consider:

 

  • What is the outcome being avoided? Death is more significant than a vertebral fracture, but different outcomes will be more or less significant to individual patients.
  • Over what period does the benefit accrue? Two drugs may have the same NNT to avoid one death, but the drug that achieves that over 6 months is more effective than the drug which takes 10 years. You can put NNTs on the same timescale by multiplying or dividing the NNT appropriately, but there is an assumption that benefit accrues consistently over time (a not unreasonable assumption, but one that is difficult to test).
  • What are the TRUE costs of the drug? This will include monetary costs, but also costs associated with treatment burden, and harm/side effects. A medicine might save the life of one of the 25 people who take it, but if it led to all 25 suffering a debilitating side effect, its costs may outweigh its benefits.

NNTs are only estimates of average benefit, and it is rarely possible to know precisely what the likely benefit will be in a particular patient. Clinicians and patients should also be aware of a degree of ‘uncertainty’ in the number since it is usually not possible to calculate valid confidence intervals around NNTs.

'Number needed to harm’ (NNH) is a related measure which is the average number of people exposed to a medication for one person to suffer an adverse event. Again, a defined end point (e.g. GI bleeding or renal failure) requires to be specified and confounders may require correction of the raw data i.e. in very elderly patients the risk of particular side effects such as confusion and falls may be higher than on average . In discussion, the overall benefit – risk ratio (NNT / NNH) requires to be ‘weighed’ in the individual patient and may vary considerably in people with polypharmacy depending on absolute risk, life expectancy and vulnerability to adverse drug events.

 

Example:

“A meta-analysis of sedative hypnotics in older people with insomnia showed that the number needed to treat for improved sleep quality was 13 and the number needed to harm for any adverse event was 6. This indicated that an adverse event is more than twice as likely as enhanced quality of sleep. Glass, J. et al. Sedative hypnotics in older people with insomnia: a meta-analysis of risks and benefits.” BMJ 2005; 331: 1169

Applicability of trial data to individual adults

Included in the Drug Efficacy chart is information on the trial population and the duration of the trial.  The closer an adult is in terms of their own characteristics and duration of treatment to the trial the more likely the trial is to give a good estimate of what they can expect to obtain from the treatment. Conversely the further away they are the less likely the information is to be applicable. This can work in both directions and treatment could be either more or less effective.

Adults approaching end of life have an increased risk of many events, so each individual event has a higher Absolute Risk. This means that interventions may have a much lower NNT for that adult. This should be balanced against the shorter time they have in life to obtain a benefit and the increased risk that any harm, even small, may have a higher impact.

Efficacy data must only be considered as one aspect of the whole drug review process keeping in mind particularly Steps 1 (objectives of treatment) and 7 (willingness for treatment) which consider the Patient Centred goals and aims in the context of their life as a whole.

 

Example:

An example would be the comparison between a ‘Frail’ and ‘Non-frail’ adult. If two adults present on the same medication and with the same range of diagnoses the answer to how effective their medication would be in terms of both benefit and harm depends on their other attributes. One may be functioning well and still working despite their ill health. The other may be more clearly nearing the end of their life and in a phase of increasingly high dependence. The latter adult is unlikely to have been represented (or even thought of) in a trial situation.

 

Areas covered by the NNT Table

Cerebrovascular / Cardiovascular Disease

Diabetes

Direct-Acting Oral Anticoagulants

Heart Failure

Hypertension

Osteoporosis