Economic evaluations of non-communicable diseases conducted in Sub-Saharan Africa: a critical review of data sources.

BACKGROUND: Policymakers in sub-Saharan Africa (SSA) face challenging decisions regarding the allocation of health resources. Economic evaluations can help decision makers to determine which health interventions should be funded and or included in their benefits package. A major problem is whether the evaluations incorporated data from sources that are reliable and relevant to the country of interest. We aimed to review the quality of the data sources used in all published economic evaluations for cardiovascular disease and diabetes in SSA. METHODS: We systematically searched selected databases for all published economic evaluations for CVD and diabetes in SSA. We modified a hierarchy of data sources and used a reference case to measure the adherence to reporting and methodological characteristics, and descriptively analysed author statements. RESULTS: From 7,297 articles retrieved from the search, we selected 35 for study inclusion. Most were modelled evaluations and almost all focused on pharmacological interventions. The studies adhered to the reporting standards but were less adherent to the methodological standards. The quality of data sources varied. The quality level of evidence in the data domains of resource use and costs were generally considered of high quality, with studies often sourcing information from reliable databases within the same jurisdiction. The authors of most studies referred to data sources in the discussion section of the publications highlighting the challenges of obtaining good quality and locally relevant data. CONCLUSIONS: The data sources in some domains are considered high quality but there remains a need to make substantial improvements in the methodological adherence and overall quality of data sources to provide evidence that is sufficiently robust to support decision making in SSA within the context of UHC and health benefits plans. Many SSA governments will need to strengthen and build their capacity to conduct economic evaluations of interventions and health technology assessment for improved priority setting. This capacity building includes enhancing local infrastructures for routine data production and management. If many of the policy makers are using economic evaluations to guide resource allocation, it is imperative that the evidence used is of the feasibly highest quality.

Antimicrobial stewardship: Prescribing across the primary care health professions.

We examined the patterns of antibiotic prescribing by medical and non-medical prescribers (dentists, nurse practitioners, and midwives) in Australia. We explored trends in the dispensed use of antibiotics (scripts and defined daily dose [DDD] per 1000 population/day) by Australian prescribers over the 12-year period, 2005-2016. We obtained data on dispensed prescriptions of antibiotics from registered health professionals subsidized on the Pharmaceutical Benefits Scheme (PBS). There were 216.2 million medical and 7.1 million non-medical dispensed prescriptions for antibiotics over 12 years. The top four antibiotics for medical prescribers were doxycycline; amoxicillin, amoxicillin plus clavulanic acid, and cefalexin, constituting 80% of top 10 use in 2005 and 2016; the top three for non-medical were amoxicillin, amoxicillin plus clavulanic acid and metronidazole (84% of top 10 use in 2016). The proportional increase in antibiotic use was higher for non-medical than medical prescribers. While medical prescribers preferentially prescribed broad-spectrum and non-medical prescribers moderate-spectrum antibiotics, there was a large increase in the use of broad-spectrum antibiotics over time by all prescribers. One in four medical prescriptions were repeats. Overprescribing of broad-spectrum antibiotics conflicts with national antimicrobial stewardship initiatives and guidelines. The proportional higher increase in antibiotic use by non-medical prescribers is a concern. To reduce inappropriate use of antibiotics and antimicrobial resistance, educational strategies targeted at all medical and non-medical prescribers are needed to align prescribing with current best practice within the scope of practice of respective prescribers.

Publicly subsidised smoking cessation medicines in times of COVID-19 in Australia: An interrupted time series analysis.

INTRODUCTION: In Australia, the available published literature demonstrated a spike in dispensed prescription medicines after the onset of the COVID-19 pandemic that subsequently returned to expected levels. Smoking cessation medicines may not follow this pattern because quit attempts are influenced by a range of factors. Knowledge of whether dispensing of these medicines has changed since the pandemic is lacking. We explored the change in dispensing of publicly subsidised smoking cessation medicines since the pandemic. METHODS: Australia's universal health-care system provides access to government-subsidised medicines via the Pharmaceutical Benefits Scheme and records of dispensed medicines are publicly available on a nationally aggregated level. We retrieved Pharmaceutical Benefits Scheme data from January 2016 to January 2021. We used interrupted time series modelling to quantify the impact of COVID-19 on dispensing of nicotine replacement therapy (NRT) patches, varenicline and all smoking cessation treatments combined separately. RESULTS: After an initial spike in medicines at the onset of the pandemic, the monthly rate of prescriptions dispensed for varenicline was predominantly within predicted ranges, while that of NRT patches was predominantly below predicted ranges. DISCUSSION AND CONCLUSIONS: There has been a differential change in the number of subsidised smoking cessation medicines supplied in Australia since the COVID-19 pandemic, with varenicline prescriptions largely within, and NRT patches largely lower than, expected ranges. The reasons for the apparent change in dispensing of subsidised smoking cessation medicines are unclear.

Dynamics of Patient-Based Benefit-Risk Assessment of Medicines in Chronic Diseases: A Systematic Review.

Background: A critical gap exits in understanding the dynamics of patient-based benefit-risk assessment (BRA) of medicines in chronic diseases during the disease journey. Purpose: To systematically review and synthesize current evidence on the changes of patients' preferences about the benefits and risks of medicines during their disease journey including the influence of disease duration and severity, and previous treatment experience. Methods: A systematic review of studies identified in PubMed and Embase, from inception to November 2020, was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Articles were eligible if they analyzed adult patient-based BRA of medicines with a chronic disease, based on at least one of the pre-specified dimensions: disease severity, disease duration, or previous treatment experience. Results: A total of 26,228 articles were identified and 105 were eligible for inclusion. Of these, 85 detected a variation in patient-based BRA of medicines with at least one of the pre-specified criteria. Patients with higher disease severity and more treatment experience have increased risk tolerance. It remains inconclusive whether disease duration directly affects the relative importance of a patient's preference. Conclusion: Factors important for patients' BRA of their medicines during a chronic disease journey vary more with their clinical situation and previous treatment experience than with time since diagnosis. Due to the importance of these factors on patients' perspectives and potential impact on their decision-making and eventually their clinical outcomes, there is a need for more studies to assess the dynamics of patients' BRA in every disease.

Antihypertensive medicine use differs between Ghana and Nigeria.

BACKGROUND: Non-communicable diseases are a growing burden in many African countries; cardiovascular disease is the main disease. Antihypertensive medicines (AHM) are a common treatment option but we know little about community use in most low- and medium-income countries (LMIC). We aimed to describe the use of antihypertensive medicines (AHM) in Ghana and Nigeria using a novel data source. METHODS: We used data from mPharma-a health and pharmaceutical company which distributes pharmaceuticals to hospital and retail pharmacies. We extracted data using the anatomical therapeutic chemical (ATC) classification codes and calculated use in defined daily doses and explored patterns by class, medicines, dose, and originator or generic product. RESULTS: AHM use differed between Ghana and Nigeria. The most used classes in Ghana were angiotensin receptor blockers (ARB) followed by calcium channel blockers (CCB) and angiotensin-converting-enzyme inhibitors (ACEi). The five most used products were 16 mg candesartan, 30 mg nifedipine, 10 mg lisinopril, 5 mg amlodipine and 50 mg losartan. In Nigeria ARB, CCB and diuretics were widely used; the top five products were 50 mg losartan, 10 mg lisinopril, 30 mg nifedipine, 40 mg furosemide, and 5 mg amlodipine. More originator products were used in Ghana than Nigeria. CONCLUSION: The differences between Ghana and Nigeria may result from a combination of medical, contextual and policy evidence and reflect factors related to clinical guidance (e.g. standard treatment guidelines), accessibility to prescribers and the role of community pharmacies, and structure of the health system and universal health coverage including funding for medicines. We show the feasibility of using novel data sources to gain insights on medicines use in the community.

Patient concerns regarding antidepressant drug–drug interactions: a retrospective analysis using data from a medicines call centre.

Introduction Antidepressant use has increased over the last two decades, with Australia and New Zealand among the highest antidepressant users in Organisation for Economic Co-operation and Development (OECD) countries. Comorbidity and polypharmacy are common in antidepressant users, increasing the likelihood of interaction-related adverse drug events, which are frequently preventable. Aim We aimed to identify, profile, and analyse potential antidepressant drug-drug interactions in information-seeking antidepressant users. Methods We retrospectively analysed antidepressant-related drug-drug interaction enquiries from patients or carers who contacted a pharmacist-led Australian national medicines call centre over an 8-year period to determine patient characteristics, concomitant drugs involved, prevalence and type of antidepressant-related drug-drug interaction across life stages, and associated risks. Results Of 3899 antidepressant drug-drug interaction calls, the most frequent concomitant drugs were antipsychotics, opioids, benzodiazepines, and complementary medicines. Narrative analyses of 2011 calls identified 81.0% of patients with potential drug-drug interactions and 10.4% categorised with worrying symptoms. The most frequent drug-drug interaction risks were excessive sedation, increased anticholinergic effects, serotonin syndrome, and suicidal thoughts. Carers of children aged Discussion Antidepressant users often have information gaps and safety concerns regarding drug-drug interactions that motivate help-seeking behaviour. Symptoms and drug-drug interaction consequences may be underestimated in these patients. Primary care health professionals have a role in proactively addressing the risk of drug-drug interactions to support benefit-risk assessment and shared decision-making.

Patient-based benefit-risk assessment of medicines: development, refinement, and validation of a content search strategy to retrieve relevant studies.

Introduction: Poor indexing and inconsistent use of terms and keywords may prevent efficient retrieval of studies on the patient-based benefit-risk assessment (BRA) of medicines. We aimed to develop and validate an objectively derived content search strategy containing generic search terms that can be adapted for any search for evidence on patient-based BRA of medicines for any therapeutic area. Methods: We used a robust multistep process to develop and validate the content search strategy: (1) we developed a bank of search terms derived from screening studies on patient-based BRA of medicines in various therapeutic areas, (2) we refined the proposed content search strategy through an iterative process of testing sensitivity and precision of search terms, and (3) we validated the final search strategy in PubMed by firstly using multiple sclerosis as a case condition and secondly computing its relative performance versus a published systematic review on patient-based BRA of medicines in rheumatoid arthritis. Results: We conceptualized a final search strategy to retrieve studies on patient-based BRA containing generic search terms grouped into two domains, namely the patient and the BRA of medicines (sensitivity 84%, specificity 99.4%, precision 20.7%). The relative performance of the content search strategy was 85.7% compared with a search from a published systematic review of patient preferences in the treatment of rheumatoid arthritis. We also developed a more extended filter, with a relative performance of 93.3% when compared with a search from a published systematic review of patient preferences in lung cancer.

Trends in Systemic Antifungal Use in Australia, 2005-2016: a Time-Series Analysis.

Data on antifungal utilization trends are important for encouraging antifungal stewardship. This study explored the use of antifungal agents for systemic application and the impact of reimbursement policy changes in Australia. We analyzed national data from the Australian Pharmaceutical Benefits Scheme (PBS) (2005-2016) and determined patterns of use over time and the impact of reimbursement decisions using an interrupted time-series model. From 2005-2016, there was an increase in the use of most antifungals, especially fluconazole, itraconazole, and posaconazole. Ketoconazole was the most commonly dispensed systemic antifungal agent (46.0%) prior to being removed from the PBS list and being replaced by fluconazole (69.8%). The PBS event "Fluconazole and itraconazole restrictions eased" led to the immediate increased use of fluconazole (0.025/1,000 per day), with both the highest rates and numerical increases attributed to obstetricians and gynecologists (1,969%; 1,851 dispensed prescriptions), as well as dermatologists (1,723%; 1,689 dispensed prescriptions) in 2010 and 2016. This is the first Australian national longitudinal estimate of systemic antifungal use. Our findings show an overall increase in the prescription of most antifungals during the investigated period, with reimbursement decisions impacting utilization. These data provide a baseline to inform the development of national antifungal guidelines and policies to encourage more targeted antifungal stewardship.

Long term impact of the WHI studies on information-seeking and decision-making in menopause symptoms management: a longitudinal analysis of questions to a medicines call centre.

BACKGROUND: While women are taking a greater role in decisions about menopause symptom management, the legacy of the Women's Health Initiative (WHI) studies persist. Despite hormone therapy (HT) being effective in reducing all-cause mortality, many women seeking relief of menopausal symptoms exaggerate HT harms and overstate the perceived benefits or ignore the risks of alternative therapies. We aimed to explore the longitudinal impact of the widely-publicised WHI 2002 study on women's information-seeking and describe determinants of decision-making about managing menopausal symptoms. METHODS: In a longitudinal analysis of both quantitative and qualitative data, we explored consumer questions about menopause-related medicines received by two Australian medicines call centres (1996-2010) before, during, and after WHI 2002. We analysed calls by age and gender of caller and patient, their relationship, postcode, enquiry type, and motivation to help-seek. We compared calls regarding HT and herbal medicines (HM) with the rest of calls, and thematically analysed question narratives across the three time-periods. RESULTS: There were 1,829 menopause-related calls received of over this time-period, with a call surge, primarily from women in their mid-fifties, in the two months after the WHI 2002 publication. Two in three calls were motivated by negative media reports as women sought support for decision-making, primarily reassurance to cease HT. While HT safety concerns persisted for eight years post-publication, the nature of information-seeking changed over time. Callers subsequently sought reassurance to use menopause treatments together with their other medicines; and pursued HT substitutes, including HM, in response to HT product discontinuation. CONCLUSIONS: Women sought information or reassurance to support a decision, based on dynamic changes in internal (symptom or risk intolerance, attitude towards menopause and treatment preferences) and external factors (perceived source trust and changes in treatment availability). In assessing HT benefit versus risk, women tend to overestimate risk with HT safety concerns persisting over time. Decision-making in managing menopause symptoms is complex and dynamic. Reassurance to reach or justify decisions from a perceived trusted source can support informed decision-making.

Using Prescription and Wastewater Data to Estimate the Correction Factors of Atenolol, Carbamazepine, and Naproxen for Wastewater-Based Epidemiology Applications.

The correction factor (CF) is a critical parameter in wastewater-based epidemiology (WBE) that significantly influences the accuracy of the final consumption estimates. However, most CFs have been derived from a few old pharmacokinetic studies and should be re-evaluated and refined to improve the accuracy of the WBE approach. This study aimed to review and estimate the CFs for atenolol, carbamazepine, and naproxen for WBE using the daily mass loads of those pharmaceuticals in wastewater and their corresponding dispensed prescription data in Australia. Influent wastewater samples were collected from wastewater treatment plants serving approximately 24% of the Australian population and annual national dispensed prescription data. The estimated CFs for atenolol and carbamazepine are 1.37 (95% CI: 1.17-1.66) and 8.69 (95% CI: 7.66-10.03), respectively. Due to significant over-the-counter sales of naproxen, a reliable CF could not be estimated based on prescription statistics. Using an independent dataset of 186 and 149 wastewater samples collected in an urban catchment in 2011 and 2012, WBE results calculated using the new CFs matched well with the dispensed data for atenolol and carbamazepine in the catchment area.

ICU Patients' Antibiotic Exposure and Triazole-Resistance in Invasive Candidiasis: Parallel Analysis of Aggregated and Individual Data.

Background: The relationship between antibiotic use and the incidence of triazole-resistant phenotypes of invasive candidiasis (IC) in critically ill patients is unclear. Different methodologies on determining this relationship may yield different results. Methods: A retrospective multicenter observational analysis was conducted to investigate exposure to antibiotics and the incidence of non-duplicate clinical isolates of Candida spp. resistant to fluconazole, voriconazole, or both during November 2013 to April 2018, using two different methodologies: group-level (time-series analysis) and individual-patient-level (regression analysis and propensity-score adjusting). Results: Of 393 identified Candida spp. from 388 critically ill patients, there were three phenotypes of IC identified: fluconazole-resistance (FR, 63, 16.0%); voriconazole-resistance (VR, 46, 11.7%); and cross-resistance between fluconazole and voriconazole (CR, 32, 8.1%). Exposure to several antibacterial agents with activity against the anaerobic gastrointestinal flora, especially third-generation cefalosporins (mainly cefoperazone/sulbactam and ceftriaxone), but not triazoles, have an immediate effect (time lag = 0) on subsequent ICU-acquired triazole-resistant IC in the group-level (p < 0.05). When the same patient database was analyzed at the individual-patient-level, we found that exposure to many antifungal agents was significantly associated with triazole-resistance (fluconazole [adjusted odds ratio (aOR) = 2.73] or caspofungin [aOR = 11.32] on FR, voriconazole [aOR = 2.87] on CR). Compared to the mono-triazole-resistant phenotype, CR IC has worse clinical outcomes (14-days mortality) and a higher level of resistance. Conclusion: Group-level and individual-patient-level analyses of antibiotic-use-versus-resistance relations yielded distinct but valuable results. Antibacterials with antianaerobic activity and antifungals might have "indirect" and "direct" effect on triazole-resistant IC, respectively.

Community-based integrated care versus hospital outpatient care for managing patients with complex type 2 diabetes: costing analysis.

Objective This study compared the cost of an integrated primary-secondary care general practitioner (GP)-based Beacon model with usual care at hospital outpatient departments (OPDs) for patients with complex type 2 diabetes. Methods A costing analysis was completed alongside a non-inferiority randomised control trial. Costs were calculated using information from accounting data and interviews with clinic managers. Two OPDs and three GP-based Beacon practices participated. In the Beacon practices, GPs with a special interest in advanced diabetes care worked with an endocrinologist and diabetes nurse educator to care for referred patients. The main outcome was incremental cost saving per patient course of treatment from a health system perspective. Uncertainty was characterised with probabilistic sensitivity analysis using Monte Carlo simulation. Results The Beacon model is cost saving: the incremental cost saving per patient was A$365 (95% confidence interval -A$901, A$55) and was cost saving in 93.7% of simulations. The key contributors to the variance in the cost saving per patient course of treatment were the mean number of patients seen per site and the number of additional presentations per course of treatment associated with the Beacon model. Conclusions Beacon clinics were less costly per patient course of treatment than usual care in hospital OPDs for equivalent clinical outcomes. Local contractual arrangements and potential variation in the operational cost structure are of significant consideration in determining the cost-efficiency of Beacon models. What is known about this topic? Despite the growing importance of achieving care quality within constrained budgets, there are few costing studies comparing clinically-equivalent hospital and community-based care models. What does this paper add? Costing analyses comparing hospital-based to GP-based health services require considerable effort and are complex. We show that GP-based Beacon clinics for patients with complex chronic disease can be less costly per patient course of treatment than usual care offered in hospital OPDs. What are the implications for practitioners? In addition to improving access and convenience for patients, transferring care from hospital to the community can reduce health system costs.

Disease modifying therapies for relapsing-remitting multiple sclerosis: Use and costs in Australia (1996-2019).

BACKGROUND: New disease modifying therapies (DMT) to control relapsing-remitting multiple sclerosis (RRMS) have been introduced to the market in the past few years and are now widely used in Australia. OBJECTIVE: To analyse the dispensed use of government subsidised RRMS DMTs in Australia from 1996 to 2019. METHODS: We obtained data of dispensed use of DMTs from the Australian Government's Pharmaceutical Benefits Scheme (PBS) administered by Medicare Australia. We measured use as defined daily dose (DDD) per 100,000 population per day. We obtained jurisdictional population data from the Australian Bureau of Statistics. RESULTS: Total DMT use increased by an average of 18% annually, from 2.4 (in 1996) to 69.9 DDD/100,000/day in 2019. Interferon ß1B was the most commonly used medicine between 1996 and 2000, Interferon ß1A between 2001 and 2014, and fingolimod subsequently. Among Australian states, Tasmania (the southernmost state) had the highest dispensed DMT use of 94.6 DDD/100,000/day in 2019. Concession beneficiaries under the Government's PBS had both lower use and cost per patient than general beneficiaries did. Fingolimod and ocrelizumab accounted for 55% of total expenditure on MS drug therapy in 2019. CONCLUSION: The use of oral DMTs might increasingly replace parenteral treatments in the near future. Given the current substantial government expenditure on oral DMTs, it will be imperative to examine the real world effectiveness of DMTs.

Duration of opioid use and association with socioeconomic status, daily dose and formulation: a two-decade population study in Queensland, Australia.

Background There is an association between the duration of prescription opioids use and an increased risk of serious harm, often unintentional. Objective (1) Describe the trends in duration of prescription opioids dispensing and, (2) determine the risk of long-term use (≥4 months) based on patients' socioeconomic status, daily dose in oral daily morphine milligram equivalent, and opioid formulation. Setting Residents of Queensland (2,827,727), Australia from the age 18 years and who were dispensed pharmaceutical opioids from 1 January 1997 to 31 December 2018. Method Retrospective, longitudinal population-based analysis using data obtained from the Monitoring of Drugs of Dependence system of the Monitored Medicines Unit of Queensland Health. Main outcome measure Contribution of socioeconomic status, and daily dose and opioid formulation (modified-release or immediate-release) to the risk of long-term opioid use. Results There was little difference between the number of patients dispensed opioids for ≥4 months and ≤3 months between 1997 and 2011. Thereafter, the number for those using opioids long-term increased. The highest risk of having opioids dispensed for ≥4 months were for patients in the lowest level of socioeconomic status (adjusted odds ratio 1.36; 95% CI, 1.34, 1.38), compared to people in the highest socioeconomic status areas, followed by the low-socioeconomic status areas, mid-socioeconomic status areas, and high-socioeconomic status areas respectively. The risk of being dispensed prescription opioids for ≥4 months significantly increased as the dose increased: adjusted odds ratio 1.73; 95% CI, 1.71, 1.75, adjusted odds ratio 1.89; 95% CI, 1.87, 1.92, and adjusted odds ratio 3.63; 95% CI, 3.58, 3.69 for the ≥20 to <50 oral daily morphine milligram equivalent, ≥50 to <100 oral daily morphine milligram equivalent and ≥100 oral daily morphine milligram equivalent dose categories, respectively. Conclusion Higher doses and living in a low socioeconomic status areas were associated with increased risk of long-term dispensing of opioid prescriptions.

Antidepressant use in Australia and Sweden-A cross-country comparison.

PURPOSE: To compare the dispensed use of antidepressants in Australia and Sweden. METHODS: We analysed publicly available data from Australia and Sweden on dispensed use of antidepressants from 2006 to 2018. RESULTS: The dispensed use of antidepressants has increased in both Australia and Sweden. Australia had a more rapid increase resulting in a higher total use. The utilisation profile was similar in both countries; SSRIs were the most commonly used group, "other antidepressants" were the group that increased the most, and seven of the eight most used substances were the same. There were differences in which antidepressants were most used, with the three most prescribed antidepressants being escitalopram, sertraline, and venlafaxine in Australia; and mirtazapine, sertraline, and citalopram in Sweden. CONCLUSION: Dispensed use of antidepressants has increased remarkably in both Australia and Sweden between 2006 and 2018. Although similar with regard to economic status and health care system, use of antidepressants differs between both countries. This may be a result of a combination of factors related to medical, contextual and policy evidence. The differences displayed in this study may reflect varying accessibility of treatments, national programmes enhancing mental health literacy in the population, clinical prescribing guidelines and timing of approval of new antidepressants.

Pharmaceutical opioids utilisation by dose, formulation, and socioeconomic status in Queensland, Australia: a population study over 22 years.

Background Prescription opioids are a central aspect of pain management and as the prevalence of pain is increasing so is the rate of use of prescription opioids. Increased opioid prescriptions increases the risk of deaths and morbidity. Objective To (a) describe the 22-year trend of prescription opioid dispensing in Queensland, (b) examine the effect of opioid dose, formulation and socioeconomic status on the number of prescriptions dispensed. Design/setting Retrospective analysis of data from the Monitoring of Drugs of Dependence system of the Monitored Medicines Unit of Queensland Health, Australia. Participants Queensland residents (3.3 million) from 18 years old dispensed 18.8 million opioid prescriptions from January 1997 to December 2018. Results Opioid prescriptions dispensed annually increased to over two million in 2018 from about 150,000 prescriptions in 1997. The number of prescriptions for modified-release formulations dispensed annually was three times higher compared to the immediate-release formulations. Oxycodone accounted for over 60% of prescriptions for pharmaceutical opioids since 2013. There was an increase in the number of prescriptions dispensed as socioeconomic status decreased and modified-release opioid formulations positively affects the pattern of dispensing. The highest increase in number of prescriptions dispensed (for all opioids) was observed among the high socioeconomic status (IRR = 1.25, 95% CI 1.25, 1.26). The disparities in the annual number of prescriptions across dose categories are wider in the modified-release than the immediate-release formulations. Conclusion The dispensing of opioids increased significantly in Queensland. There was a positive relationship between the increased dispensing of opioids and locations of lower socioeconomic status.