BACKGROUND:Listed medicines are added to the Australian Register of Therapeutic Goods conditional upon a declaration that information regarding their quality, safety and efficacy is held by the sponsor. AIM:To assess both the extent to which targeted reviews by the Therapeutic Goods Administration (TGA) as reported in compliance review reports published in 2022 and 2023 appraised the efficacy of those medicines and to document the extent of random compliance reviews from 2016. METHODS:The outcomes recorded in the 'Issues related to efficacy' section of individual compliance review reports were documented. Other matters of regulatory importance noted in the reports, such as the use of indications not permitted for these medicines, were also recorded. All random reviews in the Listed Medicine Compliance Review Reports database were documented. RESULTS:Of 215 targeted reviews, 62 recorded some degree of assessment of issues related to efficacy by the TGA. Only in six reports were there details of a critical appraisal of the sponsor's efficacy information. Further, 33 of the 62 medicines had used indications not permitted under Australian regulations. Thirty-seven random reviews between 2016 and December 2018 were identified. CONCLUSIONS:Reliance in recent years on targeted reviews has resulted in only about 2% of medicines added to the Australian Register of Therapeutic Goods having their evidence of efficacy reviewed. Use of indications not permitted for these medicines is common. Contrary to current TGA documents, no random review has been conducted since December 2018.

IntroductionThere have been substantial changes in the nature of reporting pathways and review of suspected adverse drug reactions (ADRs) in Australia since the establishment of the now defunct Advisory Committee on Safety of Medicines early in 2010.ObjectivesThe aim of this study was to (1) examine the reporting in Australia of suspected ADRs from various sources, including general practitioners (GPs), since 1990; (2) compare the reporting of Australian GPs with that in two other countries (New Zealand and the United Kingdom [UK]) with comparable safety monitoring programmes for the period 2007-2019; and (3) explore the extent to which Australian reporting of suspected adverse reactions has motivated communication to healthcare professionals in the period 1995-2019.MethodsAnnual reporting of sources of ADRs in Australia were obtained from Government reports, the Australian Statistics in Medicines and Therapeutic Goods Administration (TGA) websites. Details of the annual reporting by GPs in the UK were obtained from published sources and have been provided on request by the Medicines and Healthcare products Regulatory Agency. Details of the annual reporting by GPs in New Zealand were provided on request from the Centre for Adverse Reaction Monitoring. All issues of the Australian Adverse Drug Reactions Bulletin were accessed from the National Library of Australia, and issues of the Medicines Safety Update from February 1995 to December 2019 were accessed online from the TGA website. Each issue was searched to identify and score safety advisories.ResultsFrom 1990 to 2002 in Australia, overall reporting gradually increased, and the three major groups of reporters (GPs, hospitals and sponsors) each contributed about 30%. The relative contributions to reporting changed in the period 2002 to 2009. There was then a steep fall in reporting from GPs and the start of a very marked increase in reporting from product sponsors. GP reporting in Australia was lower than the two other comparable countries (New Zealand and the UK), and continues to fall, while in the UK at least, GP reporting is rising. The analysis of safety advisories shows a relatively stable Australian content from 1995 to 2008, followed by a sharp decline, so that by 2019 and 2020 there was barely any Australian reporting-driven content. In 1995 and 1996, Australian reports of suspected adverse reactions were the sole apparent reason for the publication of safety advisories. From 1997 to about 2008, Australian reports of suspected adverse reactions were the major reason for publication, but after this time, Australian reports became less important. During this later period, the apparent motive for publication of the safety advisory shifted to being based primarily on a publication in the medical literature, or publicity, but was sometimes based on an overseas regulator's advice or action, or action by a product sponsor.ConclusionIt is our contention that the decline in GP reporting in Australia and the current paucity in details of Australian reports in safety advisories are closely linked.

The Therapeutic Goods Administration has since 2013 neglected its long tradition of publishing regular bulletins and updates about medicine safety issues directed to Australian healthcare professionals. Recent publication policy is confused with information about clinically important safety issues published only in the alternative Safety Information Alerts and, unlike other comparable regulators, a failure to publish direct healthcare professional communications.

Background: The number needed to treat (NNT) is a medical statistic used to gauge the efficacy of therapeutic interventions. The versatility of this absolute effect measure has allowed its use in the formulation of many decision aids to support patients and practitioners in making informed healthcare choices. With the rising number of tools available to health professionals, this review synthesizes what is known of the current NNT-based tools which depict the efficacy of pharmaceutical interventions. Objective(s): To explore the current spectrum of NNT-based decision aids accessible to health professionals with a focus on the potential utility of these devices by pharmacist practitioners. Methods: A literature review was performed in MEDLINE, CINAHL, Web of Science, PsychINFO and Cochrane Library (CENTRAL, Cochrane Database of Systematic Reviews and the Cochrane Methodology Register) for studies published between January 1st 2000 and August 29th 2019. The language was restricted to English unless an appropriate translation existed. Studies that reported NNT-based decision aids of pharmaceutical or therapeutic interventions were included. One author performed study selection and data extraction. Results: A total of 365 records were identified, of which 19 NNT-based tools met the eligibility criteria, comprising of 8 tool databases and 11 individual decision aids. Decision aids appeared in multiple forms: databases, pictograms, graphs, interactive applications, calculators and charts. All aids were accessible online with a printer-friendly option, and very few came at a cost (e.g. requiring a subscription or access fee). The main tool innovators were the United Kingdom (UK) and United States (US), with English being the language of choice. Conclusions: Evidence that NNT-based decision aids can contribute to greater satisfaction and involvement of patients in medical decision making is limited and inconclusive. A case for the utilization of these tools by pharmacists has yet to be fully examined in the medical research. NNT tools may provide a valuable resource to upskill pharmacists in communication of research evidence.

Introduction Tungiasis (sand flea disease or jigger infestation) is a neglected tropical disease caused by penetration of female sand fleas, Tunga penetrans, in the skin. The disease inflicts immense pain and suffering on millions of people, particularly children, in Latin America, the Caribbean and sub-Saharan Africa. Currently, there is no standard treatment for tungiasis, and a simple, safe and effective tungiasis treatment option is required. Tea tree oil (TTO) has long been used as a parasiticidal agent against ectoparasites such as headlice, mites and fleas with proven safety and efficacy data. However, current data are insufficient to warrant a recommendation for its use in tungiasis. This trial aims to generate these data by comparing the safety and efficacy of a 5% (v/w) TTO proprietary gel formulation with 0.05% (w/v) potassium permanganate (KMnO4) solution for tungiasis treatment.Methods and analysis This trial is a randomised controlled trial (RCT) in primary schools (n=8) in South-Western Kenya. The study will include school children (n=88) aged 6–15 years with a confirmed diagnosis of tungiasis. The participants will be randomised in a 1:1 ratio to receive a 3-day two times a day treatment of either 5% TTO gel or 0.05% KMnO4 solution. Two viable embedded sandflea lesions per participant will be targeted and the viability of these lesions will be followed throughout the study using a digital handheld microscope. The primary outcome is the proportion of observed viable embedded sand fleas that have lost viability (non-viable lesions) by day 10 (9 days after first treatment). Secondary outcomes include improvement in acute tungiasis morbidities assessed using a validated severity score for tungiasis, safety assessed through adverse events and product acceptability assessed by interviewing the participants to rate the treatment in terms of effectiveness, side effects, convenience, suitability and overall satisfaction.Ethics and dissemination The trial protocol has been reviewed and approved by the University of Canberra Human Research Ethics Committee (HREC-2019-2114). The findings of the study will be presented at scientific conferences and published in a peer-reviewed journal.Trial registration numbers Australian New Zealand Clinical Trials Registry (ACTRN12619001610123); PACTR202003651095100 and U1111-1243-2294.

IntroductionIn remote Aboriginal communities in Australia, scabies affects 7 out of 10 children before their first birthday. This is more than six times the rate seen in the rest of the developed world. Scabies infestation is frequently complicated by bacterial infection, leading to the development of skin sores and other more serious consequences, such as septicaemia and chronic heart and kidney diseases. Tea tree oil (TTO) has been used as an antimicrobial agent for several decades with proven clinical efficacy. Preclinical investigations have demonstrated superior scabicidal properties of TTO compared with widely used scabicidal agents, such as permethrin 5% cream and ivermectin. However, current data are insufficient to warrant a broad recommendation for its use for the management of scabies because previous studies were small or limited to in vitro observations.Methods and analysisA pragmatic first trial will examine the clinical efficacy of a simple and low-cost TTO treatment against paediatric scabies and the prevention of associated secondary bacterial infections, with 1:1 randomisation of 200 participants (Aboriginal children, aged 5–16 years and living in remote Australia) into active control (permethrin 5% cream) and treatment (5% TTO gel) groups. The primary outcome for the study is clinical cure (complete resolution). Secondary outcome measures will include relief of symptoms, recurrence rate, adverse effects, adherence to treatment regimen and patient acceptability.Ethics and disseminationThe project has received approvals from the University of Canberra Human Research Ethics Committee (HREC 16-133), Wurli-Wurlinjang Health Service Indigenous subcommittee and the Aboriginal Medical Services Alliance Northern Territory reference group. The results of this study will be published in core scientific publications, with extensive knowledge exchange activities with non-academic audiences throughout the duration of the project.Trial registrationACTRN12617000902392; Pre-results.

Many Pacific Island countries (PICs) are recipients of funding support from the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund). However, most of these countries cannot be expected to meet Global Fund and World Health Organization (WHO) minimum requirements for a functioning pharmacovigilance (PV) system. We argue that a different approach is required to move PV forward in such countries. Although the long-term aim is to build adequate national PV capacity, we propose an approach in which resources are focused initially towards ensuring a proper system for the reporting of "problems with medicines" such as substandard and counterfeit products. The limited health system resources in these countries require that PV will be supported by some of the organizations also giving funding aid for the supply of medicines.

The importance of pharmacovigilance (PV) for safe medicines and their safe use has increasingly been recognised during the last few years [1]. PV has been subject of intense research and regulation. In particular, it has earned more and more importance and attention in low-resource countries. This is largely due to the globalisation of trade and the availability of new, highly effective but potentially harmful chemical medicinal products in those parts of the world where traditional treatments, in particular herbal or other complementary remedies, used to prevail. A plethora of publications, guidelines and information about newly observed or further investigated adverse drug reactions (ADRs) from all over the world creates a growing burden for people working with medicines or patients to keep abreast of this development. Largely due to the global availability of information through the Internet, patients are nowadays more and more critical and often concerned about, or even frightened of, potential ADRs of their medicines. This poses an additional demand on the up-todate capacities of their doctors and other healthcare professionals (HCPs). A particular challenge is the multidisciplinary character of PV which requires know-how in topics as different as molecular mechanisms of ADRs, clinical medicine, pharmacoepidemiology, information technology, pharmaceutical manufacturing, legal aspects, public health situations on various levels, and traditions in The views expressed in this article reflect a consensus reached between the personal views of all authors. They do not necessarily reflect the views of the authors’ employers or any institutions the authors are otherwise affiliated to.

National medicines policies can aid the safe use of medicines by ensuring availability of quality products, appropriate information for prescribers and consumers, strengthening the national medicines regulatory capacity and improving access to expert advice and authoritative laboratory testing. We report the findings of a workshop on medicines safety, which focused on the Asia Pacific region. Participants noted that external support is needed for resource-poor countries and that national medicines policies should include surveillance on problems with medicines, rather than the more limited monitoring of adverse drug reactions. The latter approach may be the only sensible option in countries in the Asia Pacific with very small populations.

To restrict postmarketing surveillance to a ''Potential risk: to be quantified in large-scale studies'' [1] is unusual as it excludes routine pharmacovigilance, no matter how limited that may be perceived.My study [2] showed that a lessdismissive attitude to Sub-Saharan pharmacovigilance is warranted.It appears that until late 2011, Sanofi did not give weight to the published Anglophone (from 1976) and Francophone ( 2004) case reports referenced in my paper associating extrapyramidal reactions with amodiaquine and the repeated advice (2010 and 2011) of the WHO's Advisory Committee on Safety of Medicinal Products (ACSoMP) that reporting to the Uppsala Monitoring Centre supported a clear association with artesunate amodiaquine combination products [3,4].These followed progress reports to ACSoMP of my ongoing analysis.ACSoMP recommended that the details be published and shared with the manufacturer for a possible update of the Summary of Product Characteristics [3].It is unclear whether any of the notifications mentioned by Dr Bompart [5] that led to Sanofi's acceptance of the association came from the large-scale studies.If some did, details should be published and an estimate of incidence disclosed.

BACKGROUND:Acute extrapyramidal reactions have been attributed to amodiaquine. They may be anticipated with the widely-used combination antimalarial artesunate with amodiaquine, but the association is very poorly documented.OBJECTIVE:The aim of the study was to identify individual case safety reports in the Uppsala Monitoring Centre's Vigibase™ database associating the use of the combination of artesunate and amodiaquine with extrapyramidal adverse reactions and to characterize the clinical features in those reports.METHODS:Reports of adverse reactions to the combination use of artesunate or dihydroartemisinin and amodiaquine entered into Vigibase™ up to 15 February 2011 were identified. Reports with a causality grading of 'Unlikely' and probable duplicates of reports were excluded. Reports that included at least one MedDRA® Preferred Term strongly suggestive of an extrapyramidal reaction were subject to further detailed analysis.RESULTS:Forty-three reports in adults and six reports in children were identified as associating the use of artesunate with amodiaquine, either as separate co-packaged or fixed-combination products, with extrapyramidal reactions. More than half (57%) of the adults had an onset of the reaction within 48 hours of starting treatment. Almost equal numbers of male and female adult patients were reported - 67% were aged between 14 and 30 years. The most commonly implicated daily dose was amodiaquine base 600 mg and artesunate 200 mg, but lower doses were implicated in some adult patients. Identification of very long delays in some reports reaching Vigibase™ was an unexpected observation.CONCLUSIONS:This case series supports an association of the use of artesunate and amodiaquine as combination antimalarial therapy with acute extrapyramidal reactions. The reactions occurred with recommended, and in some instances reduced, daily doses. Extrapyramidal reactions are unpleasant and frightening and the association warrants being more clearly recorded in official treatment guidelines and Summary of Product Characteristics documents.

ABSTRACTAimTo measure the rate of co‐dispensing of contraindicated drugs with cisapride 12 months prior to and 12 months after a period of publicity; and to assess the impact of the publicity, the ‘Dear Healthcare Professional letters‘, changes to the product information and pharmaceutical benefits subsidy restrictions.MethodMedicare Australia's Pharmaceutical Benefits Scheme database was searched to identify a cohort of patients who had been dispensed both cisapride and a contraindicated drug in a 12‐month period before and after a period of publicity.ResultsThe number of patients dispensed cisapride fell from 42 319 in 1998 to 2849 in 2001 after the publicity, and significantly after the restriction was placed on cisapride as a pharmaceutical benefit in 2000. In 1998, 11% of patients were dispensed a contraindicated drug 30 days after cisapride dispensing and this figure fell to 9.7% in the 2001 cohort. When the analysis was restricted to the dispensing of the specific drugs that had been named in the publicity letters (‘named’ drugs), a contraindicated drug was dispensed to 3.3% in 1998 and 2.7% in 2001.ConclusionThe large fall in the use of cisapride from 1998 to 2001 was more likely due to the pharmaceutical benefits subsidy restrictions rather than the publicity or regulatory actions during 2000. While the proportion of patients who were dispensed a contraindicated drug showed a small fall, it was unlikely to be clinically significant. When the analysis was restricted to patients who were dispensed only a ‘named’ drug, the reduction from 1998 to 2001 was small and statistically insignificant. Sponsor‐initiated communication failed to ensure optimal prescribing and dispensing of drugs.

Development of core muscle strength is important for training and during rehabilitation following injury. A Pessoa training aid (PTA) is a system of ropes and pulleys which is commonly used during equine training and rehabilitation, but there is limited information on its effectiveness. The objective of the study was to determine the effect of the PTA on the temporal, linear and angular kinematics of the working trot. Influence of testing order on effect of a PTA was assessed in four horses. Twelve riding horses were lunged at working trot on a 16 m diameter circle without (WO) and with a PTA (WP) that was set level with the shoulder. Objective measurements were carried out using high-speed motion capture (125 Hz) and inertial measurement units. Subjective video assessment was also undertaken.When a PTA was applied there was a significant reduction in speed, stride length, head angle (P < 0.0001 for all) and lumbosacral angle at maximal hindlimb retraction (P = 0.0028), but no effect on limb joint angles. The highest point of the horse was significantly different between conditions (WO, poll; WP, crest) (P = 0.0010). Dorsoventral displacement of the middle of the back (P ⩽ 0.0001) and overall impression grade (P = 0.0002) were significantly greater WP compared with WO. These findings indicated that a PTA may be beneficial for general training and rehabilitation as a method of improving posture, stimulating core muscle activation and improving overall way of going, without increasing the loading of forelimb and hindlimb structures. Further work is warranted to understand the mechanism which induces these changes.

An outbreak of hyoscine hydrobromide toxicity was detected through the Australian pharmacovigilance system. The unexpectedly wide variation in hyoscine hydrobromide content between individual tablets within single packets created difficulties in initially explaining the clinical experiences. Strict time requirements for review of incoming adverse drug reaction reports and close involvement of the highly skilled national drug regulatory laboratory resulted in early identification of the cause of the outbreak and led in turn to the identification of malpractice by the contract manufacturer.

Aim To estimate the percentage of patients dispensed alendronate who were also dispensed another drug for treatment of an upper gastrointestinal disorder ('GI' drug).Methods The Australian Health Insurance Commission (HIC) Pharmaceutical Benefits Scheme (PBS) database was searched to identify a cohort of patients for whom alendronate or calcitriol had been dispensed and had also been dispensed a GI drug.Results The number of patients dispensed a GI drug were 6.7% for alendronate and 7.5% for calcitriol with H-2-receptor antagonists accounting for the majority of usage. This difference of - 0.8% (95% confidence interval -1.6, 0.1) is not significant.Conclusion There was no excess use of GI drugs in patients taking alendronate compared with those taking calcitriol and the Australian HIC PBS database is useful for identifying large numbers of patients who have been dispensed combinations of drugs.

To estimate the incidence of pancytopenia in patients taking leflunomide with or without methotrexate in Australia.

It is an important component of any immunization programme that vaccine safety is monitored by carrying out surveillance for adverse events following immunization (AEFI). Such surveillance can be active or passive. Active surveillance will detect more AEFI, but the vast majority will be minor events. Passive surveillance is probably more appropriate for routine AEFI surveillance, while active surveillance can be used to monitor a new vaccine or to test whether a specific severe event is significantly associated with immunization. Australia has a predominantly passive surveillance system. The system has recently been centralized, providing useful national data on vaccine safety.