Rational prescribing: the principles of drug selection

Drugs in the same class (or different formulations of the same drug) may have different bioavailability, dose-concentration curves and half-lives. These factors will determine the dosing schedule. Once-daily dosing is convenient and encourages adherence. Pharmacokinetic characteristics may also influence interindividual variability in dosage requirements. For example, some drugs:

A drug with a low therapeutic index (the ratio between the dose required to cause adverse effects and that required for efficacy) is less favourable if alternatives exist. Similarly, the steepness of the dose-response curve will influence the ease with which the dose can be optimally titrated. Selectivity for a receptor subtype may be relevant when choosing drugs that avoid predictable adverse effects. Some drugs require more complex monitoring, which can affect costs and patient time (eg oral anticoagulation with warfarin requires regular INR monitoring to assess efficiency and safety while the newer oral anticoagulant apixaban does not).

Therapeutic efficacy and safety

A drug may be more efficacious in relieving symptoms, improving surrogate markers or preventing clinical events such as morbidity, mortality and hospitalisation (eg atorvastatin is more efficacious at lowering cholesterol and preventing cardiovascular disease than pravastatin) or have fewer and less serious adverse effects (eg bisoprolol has fewer serious adverse effects when used to control atrial fibrilation than amiodarone). Patients will often find it difficult to understand these comparisons because they are often expressed as relative or absolute risks. The use of the concepts of numbers needed to treat (NNT) or harm (NNH), derived from the comparison of absolute risk, will often make these comparisons of efficacy and safety more accessible.13 For example, if a drug reduces the rate of myocardial infarction over 10 years from 20% to 15% for a specific treatment group this can be expressed as an absolute risk reduction of (ARR) of 5%, a relative risk reduction (RRR) of 25% or an NNT of 20. It is the latter which, for many patients, most easily illustrates their likelihood of personally being a beneficiary of 10 years of treatment.

Large randomised controlled trials (RCTs) are considered the optimal sources of evidence. However, extrapolating the results of RCTs to prescribing decisions in the real world requires caution because RCTs usually recruit highly selected participants (eg based on age or disease severity) without comorbidities or who are not receiving interacting drugs. Such additional factors can influence efficacy or adverse outcomes, potentially reducing the former and enhancing the latter, thus limiting the external validity of RCTs.14 It is also important to recognise that some drugs have more accumulated RCT evidence than other similar drugs in the same class and this might also be a relevant factor when prescribing (eg the thiazide diuretic bendroflumethiazide has many years of accumulated experience and clinical trials data making it a more familiar choice than cyclopenthiazide for most prescribers).