Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists
The Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT) is the professional and independent society in Australia and Aotearoa New Zealand with expertise in the use and toxicity of medicines and chemicals.
ASCEPT seeks to advance health by promoting and advocating for education and research in pharmacology and toxicology and the application of these two disciplines.
Download the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists' Top-5 recommendations (PDF).
Top-5 recommendations on low-value practices
1. Recognise, rationalise or stop the prescribing cascade to reduce number of drugs which may interact.
Rationale and evidence
Rationale
A prescribing cascade refers to a situation whereby a drug adverse reaction is misdiagnosed as a new medical condition, resulting in one or more additional medicines being prescribed. This inappropriate use of medicines places the patient at risk and increases treatment costs. Examples include the initiation of an antiparkinson medicine to treat antipsychotic induced extrapyramidal side effects and the initiation of antihypertensive medicines to treat NSAID-induced hypertension. Prescribing cascades are most prevalent when multiple medicines are prescribed on a long-term basis. Older patients are at higher risk of suffering from a prescribing cascade – a variety of adverse reactions can be misdiagnosed as new geriatric syndromes such as falls, dizziness and new-onset incontinence.
Prescribers should consider the potential for an adverse effect of a newly prescribed medicine by asking patients about new symptoms. Non-pharmacological treatments should be used as initial management, rather than starting a second medicine to counteract adverse effects. To prevent the harm associated with a prescribing cascade, prescribers should place strong emphasis on prevention, detection and reversing the prescribing cascade. Strategies to do so include: conducting a medication review, starting new medicines at a low initial dose, using medicines with fewer side effects and asking questions to recognise a prescribing cascade.
Evidence
Brath H, Mehta N, Savage RD, et al. What is known about preventing, detecting, and reversing prescribing cascades: a scoping review. Journal of the American Geriatrics Society. 2018 Nov;66(11):2079-85.
Mahony D and Rochon P, Prescribing cascades: we see only what we look for, we look for only what we know. Journal of Age and Ageing, Volume 51, Issue 7, July 2022, afac138.
Rochon PA, Gurwitz JH. 'The prescribing cascade revisited'. The Lancet. 2017 May 6;389(10081):1778-80.
2. Reduce the use of medicines when there is a safer or more effective non-pharmacological management strategy.
Rationale and evidence
Rationale
Pharmacological treatments should be avoided or minimised if safe or effective non-pharmacological alternatives are available. The use of pharmacological treatments as a panacea for chronic lifestyle-related problems may detract from behaviour management tools that have proven effective in managing these same problems.
The risk of adverse effects associated with pharmacological treatments may be avoided by using non-pharmacological management strategies. For instance, in the management of chronic non-cancer pain, there is a lack of high-quality evidence supporting high doses of opioids while non-pharmacological management strategies have been shown to improve function and pain. Similarly, several types of non-pharmacological management strategies are effective in alleviating different aspects of behavioural and psychological symptoms of dementia.
Evidence
Els C, Jackson TD, Hagtvedt R et al. High-dose opioids for chronic non-cancer pain: an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2017;10:CD012299.
Skelly AC, Chou R, Dettori JR, et al. 'Noninvasive nonpharmacological treatment for chronic pain: A systematic review update'. 2020.
Li W, Xu X, Wu F, et al. Comparative efficacy of non‐pharmacological interventions on behavioural and psychological symptoms in elders with dementia: A network meta‐analysis. Nursing Open. 2021 Nov;8(6):2922-31.
3. Prescribe the minimum dose necessary for the patient to optimise the ‘benefit-to-risk’ ratio and achieve the patient’s therapeutic goals, considering individual physiology, pathophysiology, and markers of effectiveness and toxicity.
Rationale and evidence
Rationale
Therapeutic dosage should be adjusted to optimise the benefit-to-risk ratio of the treatment. Dosage should be no higher or lower than needed to achieve the patient’s therapeutic goals. Individual physiology and pathophysiology, such as age or organ dysfunction, and markers of effectiveness and toxicity, including drug concentrations where available, should be considered in any dosing decision. High drug doses aren't necessarily more effective than low doses and lower doses may prove sufficient to meet treatment goals.
Further, higher doses have an increased risk of adverse effects, particularly in older, frail patients. The effective dose 50 (ED50) is that dose which produces 50% of the desired effect in 50% of the population. It's a population parameter that can be considered in dose initiation decisions alongside the individual’s parameters. Close clinical monitoring of the desired response, drug concentrations where indicated and adverse effects, with subsequent dose adjustment is recommended to achieve the optimal dose.
Evidence
Dimmitt S, Stampfer H, and Martin J. When less is more – efficacy with less toxicity at the ED50. Br J Clin Pharmacol. 2017; 83: 1365–1368.
Stampfer H, Gabb G and Dimmitt S. 'Why maximum tolerated dose?' Br J Clin Pharmacol. 2019 Oct;85(10):2213-2217.
Warren J, Translating the dose response into risk and benefit. Br J Clin Pharmacol. 2019; 85: 2187–2193.
4. Stop medicines when no further benefit will be achieved, or the potential harms outweigh the potential benefits.
Rationale and evidence
Rationale
Pharmacological treatments should cease when there are no further benefits to be achieved from the treatment, or when the potential harms from the treatment start to outweigh the potential benefits for the individual patient. This is particularly relevant for frail elderly patients with a limited life expectancy who are at an increased risk of polypharmacy and increased drug events. In these patients, some treatments which lack evidence of benefits are unlikely to prevent disease events and may in fact lead to adverse effects that reduce quality of life.
Such common treatments include the short-term use of lipid lowering agents and osteoporosis therapies, stringent blood pressure and blood glucose control, and the use of anti-platelet agents for primary cardiovascular prevention.
People with hyperpolypharmacy are also at particular risk of treatment related harms. Prescribers can use relevant criteria (e.g., Beers Criteria and Screening Tool of Older People’s Prescriptions (STOPP) criteria) as an evaluation and decision framework for identifying, reducing or stopping potentially inappropriate medications.
Evidence
Bennett F, Ferner R, Sofat R. Overprescribing and rational therapeutics: Barriers to change and opportunities to improve. British journal of clinical pharmacology. 2021 Jan;87(1):34-8.
Pérez T, Moriarty F, Wallace E, et al. Prevalence of potentially inappropriate prescribing in older people in primary care and its association with hospital admission: longitudinal study. bmj. 2018 Nov 14;363.
Levy HB. Polypharmacy Reduction Strategies: Tips on incorporating American geriatrics society beers and screening tool of older people's prescriptions criteria. Clin Geriatr Med. 2017 May;33(2):177-187.
5. Consider the off-label use of a medicine outside clinical trials as last-line therapy, and evaluate all intended off-label use against the CATAG guiding principles.
Rationale and evidence
Rationale
Off-label prescribing involves the use of a medicine outside the TGA approved conditions for age, therapeutic indication, dosage, route, and timeframes. Off-label prescribing is associated with increased uncertainty over effectiveness and the risk of unexpected toxicity and adverse effects, especially in non-evidence based off-label drug use. A prescriber must consider the ethical and legal issues linked with off-label medicine use.
To assess the appropriateness off-label medicine use, the Council of Australian Therapeutic Advisory Groups (CATAG) recommends a critical evaluation of high-quality evidence about clinical safety: the subsequent decision regarding the process for approval, patient consent and monitoring should be informed by the level and quality of evidence supporting the use of off-label medicine. High-quality evidence supporting off-label use not only provides a strong justification, but also protect patients from harmful, ineffective and expensive treatments. The critical evaluation of evidence process should engage with an appropriate mix of expertise to optimise decisions about appropriate practice and further research.
Evidence
CATG, Rethinking medicines decision-making in Australian Hospitals: Guiding principles for high quality use off label medicines, November 2013.
Eguale T, Buckeridge DL, Verma A, et al. Association of off-label drug use and adverse drug events in an adult population. JAMA Intern Med. 2016;176(1):55–63.
Schaffer, Andrea, Bruno, Claudia, Buckley, Nicholas, et al. ‘Prescribed medicine use and extent of off-label use according to age in a nationwide sample of Australian children’, Paediatr Perinat Epidemiol. 2022.
Gazarian M, Horton DB, Carleton B, Kinlaw AC, Bushnell GA, Czaja AS, Durrieu G, Gorman EF, Titievsky L, Zito J, Slaughter JL, dosReis S. Optimizing therapeutic decision-making for off-label medicines use: a scoping review and consensus recommendations for improving practice and research. Pharmacoepidemiology and Drug Safety 2023;32(11):1200-1222.
How this list was developed
Per typical continuous improvement processes, in late 2021, P&A coordinated the refresh in collaboration with ASCEPT Council delegate PRACP Professor Jennifer Martin and other ASCEPT Council delegates following an ASCEPT internal review of its members’ clinical safety, quality and waste concerns. ASCEPT Council produced a short list of recommendations which were consistent with the existing published list but more explanatory in nature.
ASCEPT expert contacts Professor Jennifer Martin PRACP, Dr Catherine Lucas FRACP, and Dr Peter Donovan FRACP led the collection and collation of research to inform the revised ASCEPT Top-5 recommendation list via their connection with the ASCEPT SIG in clinical pharmacology. From 2021-2024 liaison between the ASCEPT contacts and P&A occurred to utilising peer reviewed sources to revise wording of list rationales. The current ASCEPT President Assoc/Prof Bridin Murnion FRACP was involved in the later stages of list refreshment and significantly contributed to the development of the new recommendations.
The list was subjected to an extensive review and consultation process that involved RACP-affiliated specialty societies. Feedback from the consultation has been integrated into the Top-5 recommendations by the ASCEPT and approved by its Council in July 2024.