Regulatory agencies worldwide have taken significant steps to expedite approval and market authorization of medicines based on their potential to address areas of significant unmet medical need and severe disease burden. However, initial approval of such medicines is often accompanied by limited evidence of benefit, posing a conundrum for payers and health systems who may desire greater certainty of their value. This paper describes a system of "accelerated access" to manage these tensions and coordinate activities across stakeholders, based on discussions held at a multi-stakeholder convening in June 2023. We focus on 6 core, near-term actions that can be taken to improve the current system: clarifying criteria for expedited regulatory approval, enhancing stakeholder coordination, creating expedited pathways in payer and health technology assessment settings, developing joint regulatory/payer/health technology assessment guidance on study design and data needs, linking pricing policy to data uncertainty, and improving patient and public understanding of the processes involved as well as the risks and benefits of the relevant medicines. Many of these actions will require additional resources and personnel, and some will necessitate unprecedented levels of coordination. Nevertheless, each action is designed to work with minimal adjustments to the current system rather than demanding an entirely new approach.

Accelerated and conditional regulatory pathways for drug approvals are intended to enable earlier patient access to potentially life-saving treatments, or treatments that provide benefits in addressing a significant unmet need. However, there are questions about how well such pathways work, how appropriately they are applied, and how the work of regulators can be better coordinated with that of health technology assessment (HTA) and payer bodies, providers and health systems, and other stakeholders. In June 2023, a multi-stakeholder, international workshop was convened in Adelaide, Australia, to deliberate the challenges, goals, and opportunities to improve accelerated access pathways. Workshop attendees included representatives from patient organizations, regulators, HTA/payer bodies, universities (ethicists, health economists), and companies developing and marketing new medicines from Australia, Asia, Europe, and North America. We reviewed the contents of this workshop to identify areas of agreement and disagreement, report the key themes of the discussion, and delineate next steps for improving accelerated access pathways. We found that there was general agreement among workshop attendees that accelerated access could be improved significantly by strengthening processes for stakeholder coordination, and that coordinated efforts will be required to implement meaningful change moving forward.

Aim The aim of this scoping review was to determine the extent of off-patent prescription medicine use beyond registered indications in various Australian clinical settings. Method The review followed the Joanna Briggs Institute approach and reported using PRISMA Extension for Scoping Reviews. Online databases were used to identify published literature about off-patent registered prescription medicines used for off-label indications in Australian public hospital, community and primary healthcare settings. In addition, empirical data from the Queensland and the South Australian state-wide medicine formularies were screened for the same medication/off-label indication dyads identified in the literature, and other locally approved uses. Results Overall, fourteen studies were included, conducted in public hospitals (n = 11), palliative care units (n = 2) and the community setting (n = 1). There were 213 reports extracted from the literature describing off-patent registered prescription medicines used for off-label indications, representing 128 unique medication/off-label indication dyads and 32 different medicines. Of these, just five medication/off-label indication dyads were approved for use on both the Queensland and South Australian state-wide medicine formularies, with 12 others only approved for use in Queensland and 16 others only approved for use in South Australia. Further examination of these state-wide formularies demonstrated that the use of off-patent registered prescription medicines beyond registered indications is more extensive than has been reported to date in the literature. There were 28 additional medication/off-label indication dyads approved on the Queensland state-wide medicine formulary and 14 such examples approved for use in South Australia. Of these, just two medication/off-label indication dyads were approved for use on both formularies. Conclusion The extent to which off-patent registered prescription medicines have been repurposed in clinical settings for off-label indications in Australia is greater than previously reported in the literature. Usage and funded availability of certain medication/off-label indication dyads, varies across Australia. These results further expose the two tiered system of medicines regulation in Australia, and its impact on equity of access to medicines. Further research is required to support policy change to encourage submission of registration updates for off-patent prescription medicines.

BACKGROUND:It is increasingly common for two or more treatments for cancer to be combined as a single regimen. Determining value and appropriate payment for such regimens can be challenging. This study discusses these challenges, and possible solutions.METHODS:Stakeholders from around the world attended a 2-day workshop, supported by a background paper. This study captures key outcomes from the discussion, but is not a consensus statement.RESULTS:Workshop attendees agreed that combining on-patent treatments can result in affordability and value for money challenges that delay or deny patient access to clinically effective treatments in many health systems. Options for addressing these challenges include: (i) Increasing the value of combination therapies through improved clinical development; (ii) Willingness to pay more for combinations than for single drugs offering similar benefit, or; (iii) Aligning the cost of constituent therapies with their value within a regimen. Workshop attendees felt that (i) and (iii) merited further discussion, whereas (ii) was unlikely to be justifiable. Views differed on the feasibility of (i). Key to (iii) would be systems allowing different prices to apply to different uses of a drug.CONCLUSIONS:Common ground was identified on immediate actions to improve access to combination regimens. These include an exploration of the legal challenges associated with price negotiations, and ensuring that pricing systems can support implementation of negotiated prices for specific uses. Improvements to clinical development and trial design should be pursued in the medium and longer term.

Objectives: Some countries make considerable effort to involve patients and patient groups in their health technology assessment (HTA) processes; others are only just considering or are yet to consider patient involvement in HTA. Methods: This commentary offers four arguments why patient involvement should be prioritized by those HTA agencies that do not yet involve patients: (1) from a patients’ rights perspective, (2) based on patient and community values, (3) centering on evidentiary contributions, and (4) from a methodological perspective. Results: The first argument builds on the Alma-Ata Declaration, which holds that patients have a right and duty to have a say in the planning and delivery of their health care, individually and collectively. Where HTA is used to determine access to technologies and services, we argue that patients have a right to be heard. The second argues that decisions about treatments and services need to be aligned with the core values and morals of the patients whom the health system serves. The third argues that patients have unique knowledge and insights about living with a health condition and their needs for services and treatments regarding that condition, which can add to the knowledge base and value of the HTA process. The fourth argues that involvement of patients can facilitate methodological advancement of HTA, in areas such as early scientific advice and managed entry with evidence development. Conclusions: An HTA process that includes patient perspectives can, therefore, provide added value to patients, policy makers and healthcare professionals alike.

OBJECTIVES:Treatment switching occurs when patients in a randomized clinical trial switch from the treatment initially assigned to them to another treatment, typically from the control to experimental treatment. This study discusses the issues this raises and possible approaches to addressing them in trials of cancer drugs. METHODS:Stakeholders from around the world were invited to a 1.5-day Workshop in Adelaide, Australia. This study attempts to capture the key points from the discussion and the perspectives of the various stakeholder groups, but is not a formal consensus statement. RESULTS:Treatment switching raises challenging ethical issues with arguments for and against allowing it. It is increasingly common in cancer drug trials and presents challenges for the interpretation of results by regulators, clinicians, patients, and payers. Proposals are offered for good practice in the design, management, and analysis of trials and wider development programs for cancer drugs in which treatment switching has occurred or is likely to. Recommendations are also offered for further action to improve understanding of the importance and challenges of treatment switching and to promote agreement between key stakeholders on guidelines and other steps to address these challenges. CONCLUSIONS:The handling of treatment switching in trials is of concern to all stakeholders. On the basis of the discussions at the Adelaide International Workshop, there would appear to be common ground on approaches to addressing treatment switching in cancer trials and scope for the development of formal guidelines to inform the work of regulators, payers, industry, trial designers and other stakeholders.

The effects of cigarette smoking and sex on theophylline clearance, elimination rate constant, and apparent volume of distribution were examined in 28 healthy, young adults given single oral doses of theophylline or aminophylline. Two-way analysis of variance showed no sex effect but a significant effect of smoking habit on theophylline clearance and elimination rate constant. Neither sex nor smoking had an effect on the apparent volume of distribution. The respective mean clearance, elimination rate constant, and volume of distribution were, in nonsmokers, 0.040 +/- 0.008 (SD) liter per hour per kg, 0.084 +/- 0.015 hr-1, 0.47 +/- 0.08 liter per kg; heavy smokers, 0.063 +/- 0.019 liter per hour per kg, 0.129 +/- 0.045 hr-1, 0.50 +/- 0.06 liter per kg; and ex-smokers, 0.051 +/- 0.10 liter per hour per kg, 0.108 +/- 0.025 hr-1, 0.49 +/- 0.08 liter per kg. Cigarette smoking appeared to induce theophylline metabolism as reflected by the mean theophylline half-life in smokers (5.4 hours) versus nonsmokers (8.3 hours). The effect of cigarette smoking on theophylline clearance may be an important consideration in the clinical use of the drug.

The Fred J Boyd Award, named in honour of SHPA’s founding president, is SHPA’s highest honour. It is awarded to an individual of high professional ideals who has made significant contributions to hospital pharmacy that benefit hospital pharmacy, and through it, humanity and the public health. LLoyd Sansom AO is the recipient of the Fred J Boyd Award for 2014. It is clear from the catalogue of LLoyd’s accomplishments during his distinguished career as an educator, a researcher and a policy advisor that he is a deserving recipient. His outstanding and sustained contribution over decades has benefitted many Australians, thanks to his influence relating toqualityuseofmedicines; there isbarely an aspect of pharmacy and medicines use in Australia in which he has not been involved nor had significant influence.Withhis input and contribution tomedicines committees at local, state and national levels, his influence is unparalleled. As a dynamic and visionary leader, LLoyd has had a major influence on pharmacy education and research. As the head of the School of Pharmacy and Medical Sciences at the University of South Australia, LLoyd instigated the transition of pharmacy education from a science focus to a clinical focus, introduced hospital-based clinical academics, was instrumental in establishing joint academic / hospital appointments, and advanced the hospital research agenda. His contribution to research has been recognised by the establishment of the Sansom Institute for Health Research, University of South Australia. As the chair of the Australian Pharmaceutical Advisory Council from 1991 to 2001, LLoyd was a driving force behind the Australian National Medicines Policy which underpins the Australian medicines system. The National Medicines Policy has four arms: Safety andQuality; Equity of Access; Quality Use of Medicines; and A Responsible and Viable Pharmaceutical Industry. His contribution and commitment to quality use of medicines continues in his current roles as a special advisor, NationalMedicines Policy Framework, Department of Health, and as the chair of the South Australian Medicines Advisory Committee. Another of LLoyd’s notable achievements was to be the first pharmacist and the longest-serving chair of the Pharmaceutical Benefits Advisory Committee (PBAC). In 2002, LLoyd was elected Officer of the Order of Australia for his ‘service to pharmacy in the development and implementation of “best practice” principles for the profession,medicationmanagement and education, and as a contributor to the development of national pharmaceutical policy’. LLoyd continues to contribute to Australian healthcare via his numerous current appointments to professional and scientific authorities: Australian Pharmaceutical Formulary; Therapeutic Goods Administration; Pharmacy BoardofAustralia,DepartmentofHealth;AustralianCommission on Safety and Quality in Health Care; Australian Pharmacy Examining Council; as a member of the Journal of Pharmacy Practice and Research Editorial Advisory Board; and so much more. Emeritus Professor LLoyd SamsonAO (L), recipient of the Fred J BoydAward 2014, with Professor Michael Dooley (SHPA Federal President). Official Journal of the Society of Hospital Pharmacists of Australia

The palliative care schedule is coming of age as evaluation data become available Palliative care is a valued aspect of clinical care, especially in general practice.1 On average, a full-time equivalent Australian general practitioner will provide care for three to five people who die an “expected” death each year — that is, people who die from end-stage organ failure, neurodegenerative disease, AIDS or cancer.2 Improving affordable community access to key medicines for palliation is a priority in the National Palliative Care Strategy, which has been endorsed by all Australian governments since 2000.3 Through the Palliative Care Medications Working Group (which takes a whole-of-sector approach that includes government, industry, clinicians and consumers), the first patient-defined schedule of the Pharmaceutical Benefits Scheme (PBS) was launched in February 2004, with the number of listings steadily growing since that time.4 This list of medicines — the palliative care schedule — was developed within existing legislation and regulations underpinned by the National Medicines Policy, which includes key tenets of access to medicines, quality use of medicines and affordability of medicines.5-7 Priority palliative care medicines had been defined in 2000, when a survey of Australian palliative care clinicians was done to seek advice on the pharmacological management of the 22 most frequently encountered symptoms and the way that medicines for these symptoms are used.8 One outcome of the survey was a list of unsubsidised medicines considered to be essential to improve community-based palliative care. The patent had expired on almost all of these medicines, limiting the commercial interests of pharmaceutical companies. Key features that were part of the design of the palliative care schedule in the PBS included: The Australian Institute of Health and Welfare recently released the first publicly available data on the costs of medicines listed on the palliative care schedule.10 The schedule provided more than $12 million worth of subsidised medicines to people at the end of life — over 150 000 prescriptions — between July 2007 and June 2012. During the 2011–12 financial year, 19 000 palliative care patients received at least one subsidised prescription for palliative care medicines. The age and geographic distribution of the patients for whom prescriptions were written closely mirror the demographic profile of people referred to specialist palliative care services in Australia, including the one-third of those who are under the age of 65 years.9,10 More than 80% of prescriptions on this program were written by GPs in the 2011–12 financial year. In order of proportion of prescriptions written, classes of medicines included: laxatives, analgesics, antiepileptics, psycholeptics, antiemetics and antinauseants, drugs for functional gastrointestinal disorders, anti-inflammatory and antirheumatic products, and stomatological preparations. More than 90% of opioid prescriptions were for the initial 4 months, and 66% of paracetamol prescriptions were for the initial 4 months. This reflects known pain trajectories at the end of life and suggests that the schedule is being used appropriately for pain medicines.11 Nationally, 161.3 subsidised palliative care-related prescriptions were dispensed per 100 000 population in the 2011–12 financial year.10 Prescription rates ranged from 99.3 per 100 000 population in the Australian Capital Territory to 250.3 per 100 000 population in Tasmania. Also, there was a more than a twofold difference in the rate of prescribing for opioids from the palliative care schedule at the end of life across the jurisdictions, and there were similar variations for most other classes of medicines prescribed. Although these are unadjusted data, adjusting for age, sex and diagnosis is unlikely to explain the differences. Possible explanations include: clinicians preferring to use using general listings in the PBS or Repatriation Pharmaceutical Benefits Scheme in some settings (ie, poor uptake of the schedule); genuine variation in use of medicines that is not easily explained by clinical characteristics; difference in levels at which public hospitals dispense medicines; and variation in the proportion of care provided in primary and specialist care services. The uptake of the program is quite low. On average, for people who had any prescriptions written, only 1.9 prescriptions were written per person.12 In the last full year reported, only 19 293 people had any prescriptions written. Conservatively, the number of people who had any prescriptions written is fewer than half of the number of those predicted to die an expected death in Australia annually, and this estimate is reinforced by the number of people who currently are seen by specialist palliative care services.12 In the last 40 days of life, there is a 50% increase in prescribing for symptom control medicines, from a baseline average of 2.5 medicines.13 Prescriptions written from the general section of the PBS therefore still account for the majority of prescriptions written for people at the end of life. Further, this suggests that the palliative care schedule is being used appropriately for specific indications or increased volumes per prescription. The federal government is to be commended because this schedule is delivering on the original policy intent of making medicines essential for symptom control more affordable for people at the end of life. A key sign of the long-term viability of this initiative is that there have been specific applications by pharmaceutical companies for listings in the schedule. Not commissioned; externally peer reviewed. No relevant disclosures.

Pharmaceutical companies have a good understanding of the needs and requirements of regulatory bodies, but the evidence expectations of health technology assessment (HTA) and coverage/payer bodies are less well understood and addressed. This paper seeks to improve this understanding by providing an overview of the expectations of HTA and coverage/payer bodies, explaining how and why these differ from those of regulators, and describing the extent and limitations of work on harmonization. The article goes on to describe ways in which HTA and coverage/payer bodies’ expectations can be addressed, and to encourage industry to interact with HTA and coverage/payer bodies to increase mutual understanding and hence promote more efficient development of and access to innovative medicines.

In this study, lead (Pb) bioaccessibility was assessed in peri-urban contaminated soils using a variety of established in vitro assays. Bioaccessibility data was then used to predict Pb relative bioavailability (RBA) using published in vivo-in vitro regression models in order to compare calculated estimates and measured values. Lead bioaccessibility varied depending on the in vitro methodology employed with the relative bioavailability leaching procedure (RBALP) and in vitro gastrointestinal (IVG) assays providing more conservative Pb bioaccessibility values compared to those determined using PBET, UBM and Rel-SBRC-I assays. When Pb RBA was calculated, predicted values using PBET-G and UBM-G data were similar to measured Pb RBA values. However, Pb RBA was over-estimated by 1.6-5.5- and 2.6-6.6-fold when data and regression models from RBALP and IVG-G assays were employed.

There is an expectation that the value of a new technology will be considered by decision makers in determining whether to provide subsidy. What constitutes the elements of value and how these may be weighted is not transparent, however, and further work needs to be done to determine the circumstances and mechanisms of their application. In the end, judgment will still be needed even if greater formalization of the value construct is developed.

The last ten years have seen considerable advances in increasing transparency and opportunities for consumers and others to input into the PBAC.

Journal of Pharmacy Practice and ResearchVolume 40, Issue 2 p. 88-89 EditorialFree Access Pharmacists, Pharmacovigilance, Unapproved Indications and the TGA Emeritus Professor Lloyd Sansom AO, DipPharm, BSc, PhD, Hon DHlth, Hon DUniv, Hon DSc, FPS, Emeritus Professor Lloyd Sansom AO, DipPharm, BSc, PhD, Hon DHlth, Hon DUniv, Hon DSc, FPS Editorial Advisory Board Member, Journal of Pharmacy Practice and Research, and Chair, Pharmaceutical Benefits Advisory Committee, and Emeritus Professor [email protected] Division of Health Sciences, University of South Australia, North Terrace, SA, 5000Search for more papers by this author Emeritus Professor Lloyd Sansom AO, DipPharm, BSc, PhD, Hon DHlth, Hon DUniv, Hon DSc, FPS, Emeritus Professor Lloyd Sansom AO, DipPharm, BSc, PhD, Hon DHlth, Hon DUniv, Hon DSc, FPS Editorial Advisory Board Member, Journal of Pharmacy Practice and Research, and Chair, Pharmaceutical Benefits Advisory Committee, and Emeritus Professor [email protected] Division of Health Sciences, University of South Australia, North Terrace, SA, 5000Search for more papers by this author First published: 13 April 2015 https://doi.org/10.1002/j.2055-2335.2010.tb00509.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. References 1 Therapeutic Goods Administration. Access to unapproved therapeutic goods via the Special Access Scheme. Canberra: Therapeutic Goods Administration; 2009. Available from . 2 Medicines Australia. Code of conduct. Edition 14 guidelines. Version 1. Canberra: Medicines Australia; 2003. Available from . 3 Department of Health and Ageing. Life saving drug program. Canberra: Commonwealth of Australia; 2007. Available from . 4 National Institute of Clinical Excellence. Neuropathic pain: the pharmacological management of neuropathic pain in adults in non-specialist settings. London: National Institute of Clinical Excellence; 2010. Available from . 5 Caring for Australasians with Renal Impairment. CARI guidelines. Sydney: Caring for Australasians with Renal Impairment; 2010. Available from . 6 Cancer Institute of NSW. Chemotherapy patient information: Hodgkin's lymphoma (advanced). Sydney: NSW Government; 2010. Available from . 7 Cancer Institute of NSW. Chemotherapy patient information: Hodgkin's lymphoma (early stage). Sydney: NSW Government; 2010. Available from . 8 Approved Product Information. Dacarbazine for injection. Canberra: Therapeutic Goods Administration; 2009. Available from . Citing Literature Volume40, Issue2June 2010Pages 88-89 ReferencesRelatedInformation

In this study, the bioaccessibility and relative bioavailability of soil8borne contaminants were compared to determine whether a simple rapid, inexpensive in vitro assay may be used to predict in-vivo relative bioavailability for human health exposure assessment. Arsenic, cadmium and lead bioaccessibility in contaminated soil was assessed using a variety of in-vitro assays (SBRC, IVG, PBET and DIN) incorporating gastric (G) and intestinal phases (I) while in-vivo relative bioavailability was determined using mouse or swine assays. When linear regression models were developed in order to determine the suitability of in-vitro assays for predicting arsenic, cadmium and lead relative bioavailability, the correlation between bioaccessibility and relative bioavailability varied depending on the methodology used. While arsenic, cadmium and lead relative bioavailability could be accurately predicted using SBRC8G, PBET8I and Rel8 SBRC8I respectively, a single in-vitro method was not suitable for predicting relative bioavailability for all three contaminants.

Internationally, there is a growing use of cost-effectiveness analysis as part of the decision-making process for the subsidy of pharmaceuticals. This will continue as the cost of pharmaceuticals and the demands for health services increase within constrained financial frameworks and as the need to consider opportunity costs becomes more essential. Third party payers consists of governments (e.g. in the UK and Australia) or private health insurance agencies. The data needs of these payers have generally not been acknowledged by the pharmaceutical industry, which has concentrated on registration of the medicine as the primary focus of the drug development process. As the costs increase, the capacity of the individual patient to pay for these medicines becomes limited and new medicines will generally not have a market unless they are subsidized. Sponsors must now consider the data requirements of payers as part of the drug development process and payers will need to be more active in their dialogue with sponsors regarding these requirements, with a view to the development of an international framework similar to that which exists for data requirements for registration purposes. The growing use of conditional or controlled access by patients with requirements for further data collection as a means of addressing uncertainty will require a greater interaction between regulators, payers and sponsors. There seems to be a divide between regulators and payers, an absence of overt willingness to participate in an international dialogue to discuss issues of common interest and a divergence of philosophy rather than a uniqueness of the issues. All stakeholders need to work together to improve the efficiency of drug evaluation processes to ensure that patients have timely access to safe and effective medicines at a price they and their nations can afford.