In Australia, government-subsidised access to high-cost medicines is "targeted" to particular sub-sets of patients under the Pharmaceutical Benefits Scheme to achieve cost-effective use. In order to determine how this access system could be improved, the opinions of key stakeholders on access to biological agents for rheumatoid arthritis were explored.
Thirty-six semi-structured interviews were conducted with persons from relevant stakeholder groups. These were transcribed verbatim, and analysed thematically.
Controlled access to expensive medicines was considered to be equitable and practical; however, there was disagreement as to the method of defining the target patient populations. Other concerns included timeliness of access, excessive bureaucracy, and the need for additional resources to facilitate the scheme. Collaboration between stakeholders was deemed important because it allows more equitable distribution of limited resources. The majority considered that stakeholder consultation should have been broader. Most wanted increased transparency of the decision-making process, ongoing and timely review of access criteria, and an increased provision of information for patients. More structured communication between stakeholders was proposed.
The Pharmaceutical Benefit Scheme is adapting to meet the changing needs of patients. Provision of subsidised access to high-cost medicines in a manner that is affordable for individuals and society, and that is equitable and efficiently managed is challenging. The views of stakeholders on targeted access to anti-rheumatic biological medicines in Australia acknowledged this challenge and provided a number of suggestions for modifications. These could serve as a basis to inform the debate on how to change the processes and policies so as to improve the scheme.
TNF inhibitors (TNFi) have revolutionised the treatment of rheumatoid arthritis (RA). Natural killer (NK) cells and Natural Killer Cell Receptor+ T (NKT) cells comprise important effector lymphocytes whose activity is tightly regulated through surface NK receptors (NKRs). Dysregulation of NKRs in patients with autoimmune diseases has been shown, however little is known regarding NKRs expression in patients with TNFi-induced remission and in those who maintain remission vs disease flare following TNFi withdrawal.
Patients with RA were recruited for this study, (i) RA patients in clinical remission following a minimum of one year of TNFi therapy (n = −15); (2) Active RA patients, not currently or ever receiving TNFi (n = 18); and healthy control volunteers (n = 15). Patients in remission were divided into two groups: those who were maintained on TNFi and those who withdrew from TNFi and maintained on DMARDS. All patients underwent full clinical assessment. Peripheral blood mononuclear cells were isolated and NKR (CD94, NKG2A, CD161, CD69, CD57, CD158a, CD158b) expression on T-(CD3+CD56−), NK-(CD3−CD56+) and NKT-(CD3+CD56+) cells was determined by flow cytometry.
Following TNFi withdrawal, percentages and numbers of circulating T cells, NK cells or NKT cell populations were unchanged in patients in remission versus active RA or HCs. Expression of the NKRs CD161, CD57, CD94 and NKG2A was significantly increased on CD3+CD56-T cells from patients in remission compared to active RA (p<0.05). CD3+CD56-T cell expression of CD94 and NKG2A was significantly increased in patients who remained in remission compared with patients whose disease flared (p<0.05), with no differences observed for CD161 and CD57. CD3+CD56− cell expression of NKG2A was inversely related to DAS28 (r = −0.612, p<0.005).
High CD94/NKG2A expression by T cells was demonstrated in remission patients following TNFi therapy compared to active RA, while low CD94/NKG2A were associated with disease flare following withdrawal of therapy.
Several prior investigations demonstrate an improvement in bone mineral density associated with use of TNF inhibitors (TNFi). We compared the risk of osteoporotic fractures among patients with rheumatoid arthritis (RA) initiating a disease-modifying antirheumatic drug (DMARD).
A population-based cohort study was conducted using health care utilization data (1996–2008) from a Canadian province and a US commercial insurance plan. Patients with at least two RA diagnoses were identified and follow-up began with the first prescription for a DMARD. Drug regimens were categorized into three mutually exclusive hierarchical groups: 1) TNFi with or without non-biologic DMARDs (nbDMARD), 2) methotrexate (MTX) without a TNFi, or 3) other nbDMARD without a TNFi or MTX. Main outcomes were hospitalizations for fractures of the hip, wrist, humerus, or pelvis based on diagnoses and procedure codes.
The study cohort consisted of 16,412 RA patients with 25,988 new treatment episodes: 5,856 TNFi, 12,554 MTX, and 7,578 other nbDMARD. The incidence rate per 1,000 person-years for osteoporotic fracture were 5.11 (95% CI 3.50 – 7.45) for TNFi, 5.35 (95% CI 4.08–7.02) for MTX, and 6.38 (95% CI 3.78–10.77) for other nbDMARD. After multivariable adjustment for osteoporosis and fracture-related risk factors, the risk of non-vertebral osteoporotic fracture was not different in either TNFi (hazard ratio (HR) 1.07, 95% CI 0.57–1.98) or MTX (HR 1.18, 95% CI 0.60– 2.34) compared with nbDMARD.
Among subjects diagnosed with RA, the adjusted risk of non-vertebral fracture was similar across persons starting a TNFi, MTX, or other nbDMARD.
rheumatoid arthritis; fracture; disease modifying antirheumatic drugs
Objectives. Adalimumab, etanercept and infliximab are effective TNF inhibitors (TNFis) in the treatment of RA, but no randomized clinical trials have compared the three agents. Prior observational data are not consistent. We compared their effectiveness over 1 year in a prospective cohort.
Methods. Analyses were performed on subjects’ first episode of TNFi use in the Rheumatic Diseases Portuguese Register, Reuma.pt. The primary outcome was the proportion of patients with European League Against Rheumatism good response sustained at two consecutive observations separated by 3 months during the first year of TNFi use. Comparisons were performed using conventional adjusted logistic regression, as well as matching subjects across the three agents using a propensity score. In addition, baseline predictors of treatment response to TNFi were identified.
Results. The study cohort included 617 RA patients, 250 starting etanercept, 206 infliximab and 161 adalimumab. Good response was achieved by 59.6% for adalimumab, 59.2% for etanercept and 51.9% for infliximab (P = 0.21). The modelled probability of good response did not significantly differ across agents (etanercept vs adalimumab OR = 0.97, 95% CI 0.55, 1.71; etanercept vs infliximab OR = 1.25, 95% CI 0.74, 2.12; infliximab vs adalimumab OR = 0.80, 95% CI 0.47, 1.36). Matched propensity score analyses also showed no significant treatment response differences. Greater educational attainment was a predictor of better response, while smoking, presence of ACPA, glucocorticoid use and worse physician assessment of disease activity at baseline each predicted a reduced likelihood of treatment response.
Conclusion. Over 1 year, we found no difference in effectiveness between adalimumab, etanercept and infliximab.
RA; TNF inhibitors; comparative effectiveness; Reuma.pt register; response predictors
Subsidised access to high-cost medicines in Australia is restricted under national programs (the Pharmaceutical Benefits Scheme, PBS, and the Repatriation Pharmaceutical Benefits Scheme, RPBS) with a view to achieving cost-effective use. The aim of this study was to examine the use and associated government cost of biological agents for treating rheumatoid arthritis over the first two years of subsidy, and to compare these data to the predicted outcomes.
National prescription and expenditure data for the biologicals, etanercept, infliximab, adalimumab, and anakinra were collected and analysed for the period August 2003 to July 2005. Dispensing data on biologicals sorted by the metropolitan, rural and remote zones and by prescriber major specialty were also examined.
A total of 27,970 prescriptions for biologicals was reimbursed. The government expenditure was A$53.1 million, representing only 19% of that expected. Almost all prescriptions were reimbursed by the PBS (98%, A$52 million) and the remainder by the RPBS. Approximately 62% of the prescriptions were for concessional patients (A$32.9 million). There was considerable variability in the use of biologicals across Australian states and territories, usage roughly correlating with the per capita adjusted number of rheumatologists. The total number of prescriptions continued to increase over the study period. Etanercept was the most highly prescribed agent (74% by number of prescriptions), although its use was beginning to plateau. Use of adalimumab increased steadily. Use of infliximab and anakinra was considerably lower. The resultant health outcomes for individual patients are unknown. Prescribers from capital cities and other metropolitan centres provided a majority of prescriptions of biologicals (89%).
The overall uptake of biologicals for treating rheumatoid arthritis over the first two years of PBS subsidy was considerably lower than expected. Long-term safety concerns and the expanded clinical uses of these drugs emphasise the need for evaluation. It is essential that there is comprehensive, ongoing analysis of utilisation data, associated expenditure and, importantly, patient outcomes in order to enhance accountability, efficiency and equity of policies that allocate substantial resources to subsidising national access to high-cost medicines.
To evaluate the safety and efficacy of tocilizumab in clinical practice in patients with rheumatoid arthritis (RA) with inadequate responses (IR) to disease-modifying antirheumatic drugs (DMARDs) or both DMARDs and tumour necrosis factor α inhibitors (TNFis).
Patients—categorised as TNFi-naive, TNFi-previous (washout) or TNFi-recent (no washout) —received open-label tocilizumab (8 mg/kg) every 4 weeks ± DMARDs for 24 weeks. Adverse events (AEs) and treatment discontinuations were monitored. Efficacy end points included American College of Rheumatology (ACR) responses, 28-joint disease activity score (DAS28) and European League Against Rheumatism responses.
Overall, 1681 (976 TNF-naive, 298 TNFi-previous and 407 TNFi-recent) patients were treated; 5.1% discontinued treatment because of AEs. The AE rate was numerically higher in TNFi-recent (652.6/100 patient-years (PY)) and TNFi-previous (653.6/100PY) than in TNFi-naive (551.1/100PY) patients. Serious AE rates were 18.0/100PY, 28.0/100PY and 18.6/100PY; serious infection rates were 6.0/100PY, 6.8/100PY and 4.2/100PY, respectively. At week 4, 36.5% of patients achieved ACR20 response and 14.9% DAS28 remission (<2.6); at week 24, 66.9%, 46.6%, 26.4% and 56.8% achieved ACR20/ACR50/ACR70 responses and DAS28 remission, respectively. Overall, 61.6% (TNFi-naive), 48.5% (TNFi-previous) and 50.4% (TNFi-recent) patients achieved DAS28 remission.
In patients with RA who were DMARD-IR/TNFi-IR, tocilizumab ± DMARDs provided rapid and sustained efficacy without unexpected safety concerns.
To investigate the frequency of lipid testing in clinical practice and explore the relationship between rheumatoid arthritis (RA), dyslipidemia, and other cardiovascular (CV) risk factors, with RA treatment.
Patients in the retrospective database study were ≥18 years old and had ≥2 physician diagnoses for RA or osteoarthritis (OA) [comparator group] between March 2004-March 2008. Outcomes of interest included the percentage of RA and OA patients receiving lipid tests, lipid profiles (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]) of RA vs. OA patients, and lipid profiles of RA patients before and after initiation with a tumor necrosis factor inhibitor (TNFi). We used multivariable regression to control potential confounders between the cohorts.
Over a median 2+ year follow-up, fewer RA patients than OA patients had at least one lipid test (62% [95% CI, 60-64] vs. 68% [95% CI, 65-71]). Mean TC and LDL-C were each 4 mg/dL lower in the RA cohort (P<0.0001); HDL-C was similar between cohorts. Across the RA cohort, 25.2% of patients had suboptimal LDL-C levels (≥130 mg/dL). Among RA patients not using lipid-lowering therapy who initiated TNFi therapy (n=96), mean TC and LDL-C increased by 5.4 and 4.0 mg/dL, respectively.
RA patients were less likely to be tested for hyperlipidemia and had more favorable lipid profiles than OA patients. TNFi therapy modestly increased all lipid parameters. Additional studies are needed to determine the effect of traditional CV risk factors, inflammation, and the impact of biologics on CV outcomes in RA patients.
Objective. To investigate the effect of tocilizumab on patient-reported outcomes (PROs) in RA patients with inadequate responses to TNF inhibitors (TNFis).
Methods. In a Phase III randomized controlled trial, 489 patients received 4 or 8 mg/kg tocilizumab or placebo every 4 weeks plus MTX for 24 weeks. Mean changes from baseline over time and proportions of patients reporting improvements greater than or equal to minimum clinically important differences (MCIDs) in PROs were analyzed.
Results. At week 24, 8 mg/kg resulted in significantly greater improvements vs placebo in pain, global assessment of disease activity (P = 0.001), Health Assessment Questionnaire-Disability Index (HAQ-DI; P < 0.0001), Functional Assessment of Chronic Illness Therapy-Fatigue (P = 0.0150) and Medical Outcomes Survey Short Form 36 (SF-36 v2) Physical Component Summary (PCS; P = 0.0003) scores, all greater than MCID; 4 mg/kg resulted in greater improvements in pain (P = 0.0100), HAQ-DI (P = 0.0030) and SF-36 PCS (P = 0.0020) scores. Tocilizumab-associated improvements were evident as early as week 2. At week 24, more tocilizumab-treated than control patients reported improvements greater than or equal to MCID in SF-36 domain scores and related PROs (50.9–84.9% vs 35.0–51.7%) and achieved ACR50 responses and/or Disease Activity Score 28 (DAS28) remission with PRO improvements greater than or equal to MCID (36.2–51.2% vs 10–20.7% and 10.7–37.5% vs 0.0–3.4%, respectively).
Conclusion. Tocilizumab treatment in patients with inadequate responses to TNFis resulted in rapid and sustained improvements in multiple PROs that were statistically significant and clinically meaningful, consistent with previous efficacy reports.
Trial Registration. ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00106522.
rheumatoid arthritis; tocilizumab; health-related quality of life; patient-reported outcomes; randomized controlled trial
Access to "high cost medicines" through Australia's Pharmaceutical Benefits Scheme (PBS) is tightly regulated. It is inherently difficult to apply any criteria-based system of control in a way that provides a fair balance between efficient use of limited resources for community needs and equitable individual access to care. We suggest, in relation to very high cost medicines, that the present arrangements be re-considered in order to overcome potential inequities. The biological agents for the treatment of rheumatoid arthritis are used as an example by which to discuss the ethical issues associated with the current scheme. Consideration of ethical aspects of the PBS and similar programs is important in order to achieve the fairest outcomes for individual patients, as well as for the community.
On 1 January 2005, a controversial trade agreement entered into force between Australia and the United States. Though heralded by the parties as facilitating the removal of barriers to free trade (in ways not achievable in multilateral fora), it also contained many trade-restricting intellectual property provisions and others uniquely related to altering pharmaceutical regulation and public health policy in Australia. The latter appear to have particularly focused on the world-respected process of federal government reimbursement after expert cost-effectiveness evaluation, popularly known as the Pharmaceutical Benefits Scheme ('PBS'). It remains uncertain what sort of impacts – if any – the Australia-United States Free Trade Agreement ('AUSFTA') will have on PBS processes such as reference pricing and their important role in facilitating equitable and affordable access to essential medicines.
This is now the field of inquiry for a major three year Australian Research Council ('ARC')-funded study bringing together a team of senior researchers in regulatory theory from the Australian National University and pharmacoeconomics from the University of Newcastle. The project proposes to monitor, assess and analyse the real and potential impacts of the AUSFTA in this area, providing Australian policy-makers with continuing expertise and options.
To the extent that the AUSFTA medicines provisions may represent an
important precedent in a global strategy by industry on
cost-effectiveness evaluation of pharmaceuticals, the study will also be
of great interest to policy makers in other jurisdictions.
The access to healthcare and treatment by rheumatoid arthritis (RA) patients, particularly to biologics, differs significantly among European countries.
We aimed to explore the views and experiences of Portuguese healthcare stakeholders on key barriers which limit the access to treatment, and ultimately to biologics, by RA patients and to find potential solutions (leverage points) to overcome the identified barriers.
This was a qualitative research consisting of semi-structured face-to-face interviews with key stakeholders in RA framework. Thirty four individuals from eight groups of stakeholders were interviewed: rural and urban general practitioners (GPs), rheumatologists, hospital managers, hospital pharmacists, budget holders, representatives from the Portuguese Rheumatology Society and the RA Patient Association. Interviews were conducted between May and June 2011. Conventional content analysis with research triangulation was used.
The key barriers identified were related to the accessibility to primary healthcare services, difficulties in RA diagnosis among GPs, inefficient referral to secondary healthcare and controlled process of biologics prescription in public hospitals. The leverage points identified included the improvement of epidemiological and clinical knowledge about RA in Portugal, a better understanding of the disease among patients and GPs, the clarification of biologics benefits among budget holders and a raised awareness of the current treatment guidelines. In order to further address the leverage points, the following key initiatives were proposed: optimization of RA national registry; dissemination of information on rheumatic symptoms in primary care facilities and among the general public; increase interaction between rheumatologists and GPs through clinical discussions of successfully treated patients or workshops; broader utilization of disease diagnosis and monitoring tools, such as DAS28, and implementation of hospital–based research to collect real-world data.
Most of the key barriers limiting the access to treatment, including biologics, in RA in Portugal are upstream of rheumatology practice. Our findings suggest that future actions should be focused on the primary care level to improve referral to rheumatologists. In addition, the collection of real-world data seems essential to characterise the RA population, to improve disease management and to increase compliance with current treatment guidelines.
Rheumatoid arthritis; Biologics; Access to treatment; Qualitative research; Stakeholders
Suppression of the immunoinflammatory cascade by targeting interleukin 6 (IL-6) mediated effects constitutes a therapeutic option for chronic inflammatory diseases. Tocilizumab is the only IL-6 inhibitor (IL-6i) licensed for rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), but also other agents targeting either IL-6 or its receptor are investigated in various indications.
To review published evidence on safety and efficacy of IL-6i in inflammatory diseases.
We performed systematic literature searches in Medline and Cochrane, screened EULAR and American College of Rheumatology meeting-abstracts, and accessed http://www.clinicaltrials.gov.
Comprehensive evidence supports the efficacy of tocilizumab in RA in DMARD-naïve patients, and after DMARD- and TNFi-failure. Randomised comparisons demonstrate superiority of tocilizumab in JIA, but not ankylosing spondylitis (AS). Other indications are currently investigated. Additional IL-6i show similar efficacy; safety generally appears acceptable.
IL-6i is effective and safe in RA and JIA, but not in AS. Preliminary results in other indications need substantiation.
Rheumatoid Arthritis; Juvenile Idiopathic Arthritis; Treatment; DMARDs (biologic)
Inflammatory bowel disease (IBD) is a group of chronic disorders of the gastrointestinal tract comprising Crohn’s disease (CD) and ulcerative colitis (UC). Their etiologies are unknown, but they are characterised by an imbalanced production of pro-inflammatory mediators, e.g., tumor necrosis factor (TNF)-α, as well as increased recruitment of leukocytes to the site of inflammation. Advantages in understanding the role of the inflammatory pathways in IBD and an inadequate response to conventional therapy in a large portion of patients, has over the last two decades lead to new therapies which includes the TNF inhibitors (TNFi), designed to target and neutralise the effect of TNF-α. TNFi have shown to be efficient in treating moderate to severe CD and UC. However, convenient alternative therapeutics targeting other immune pathways are needed for patients with IBD refractory to conventional therapy including TNFi. Indeed, several therapeutics are currently under development, and have shown success in clinical trials. These include antibodies targeting and neutralising interleukin-12/23, small pharmacologic Janus kinase inhibitors designed to block intracellular signaling of several pro-inflammatory cytokines, antibodies targeting integrins, and small anti-adhesion molecules that block adhesion between leukocytes and the intestinal vascular endothelium, reducing their infiltration into the inflamed mucosa. In this review we have elucidated the major signaling pathways of clinical importance for IBD therapy and highlighted the new promising therapies available. As stated in this paper several new treatment options are under development for the treatment of CD and UC, however, no drug fits all patients. Hence, optimisations of treatment regimens are warranted for the benefit of the patients either through biomarker establishment or other rationales to maximise the effect of the broad range of mode-of-actions of the present and future drugs in IBD.
Anti-tumor necrosis factor; Biologics; Crohn’s disease; Pro-inflammatory cytokines; Signaling pathways; Treatment; Ulcerative colitis
In September 2003, the Canadian government committed to developing legislation that would facilitate greater access to affordable medicines for developing countries. Over the course of eight months, the legislation, now known as Canada's Access to Medicines Regime (CAMR), went through a controversial policy development process and the newspaper media was one of the major venues in which the policy debates took place. The purpose of this study was to examine how the media framed CAMR to determine how policy goals were conceptualized, which stakeholder interests controlled the public debate and how these variables related to the public policy process.
We conducted a qualitative content analysis of newspaper coverage of the CAMR policy and implementation process from 2003-2008. The primary theoretical framework for this study was framing theory. A total of 90 articles from 11 Canadian newspapers were selected for inclusion in our analysis. A team of four researchers coded the articles for themes relating to access to medicines and which stakeholders' voice figured more prominently on each issue. Stakeholders examined included: the research-based industry, the generic industry, civil society, the Canadian government, and developing country representatives.
The most frequently mentioned themes across all documents were the issues of drug affordability, intellectual property, trade agreements and obligations, and development. Issues such as human rights, pharmaceutical innovation, and economic competitiveness got little media representation. Civil society dominated the media contents, followed far behind by the Canadian government, the research-based and generic pharmaceutical industries. Developing country representatives were hardly represented in the media.
Media framing obscured the discussion of some of the underlying policy goals in this case and failed to highlight issues which are now significant barriers to the use of the legislation. Using the media to engage the public in more in-depth exploration of the policy issues at stake may contribute to a more informed policy development process. The media can be an effective channel for those stakeholders with a weaker voice in policy deliberations to raise public attention to particular issues; however, the political and institutional context must be taken into account as it may outweigh media framing effects.
In Iran medical students are selected from high school graduates via a very competitive national university entrance exam. New proposals have been seriously considered for admitting students from those with bachelor degrees. We assessed the opinions of different stakeholders on the current situation of admission into medicine in Iran, and their views on positive and negative aspects of admitting graduates into medicine.
We conducted five focus group discussions and seven in-depth interviews with stakeholders including medical students, science students, university professors of basic sciences, medical education experts, and policy makers. Main themes were identified from the data and analyzed using content analysis approach.
Medical students believed "graduate admission" may lead to a more informed choice of medicine. They thought it could result in admission of students with lower levels of academic aptitude. The science students were in favor of "graduate admission". The education experts and the professors of basic science all mentioned the shortcomings of the current system of admission and considered "graduate admission" as an appropriate opportunity for correcting some of the shortcomings. The policy makers pointed out the potential positive influences of "graduate admission" on strengthening basic science research. They thought, however, that "graduate admission" may result in lengthening the overall duration of medical education, which is already long in Iran (over 7 years). On the whole, the participants thought that "graduate admission" is a step in the right direction for improving quality of medical education.
"Graduate admission" has the potential to correct some of shortcomings of medical education. Unlike other countries where "graduate admission" is used mainly to admit students who are mentally mature, in Iran the main objective seems to be strengthening basic sciences.
More than two billion people in low- and middle-income countries (LMIC) lack adequate access to essential medicines. In this paper, we make strong public health, human rights and economic arguments for improving access to medicines in LMIC and discuss the different roles and responsibilities of key stakeholders, including national governments, the international community, and non-governmental organizations (NGOs). We then establish a framework of pharmaceutical firms’ corporate responsibilities - the “must,” the “ought to,” and the “can” dimensions - and make recommendations for actionable business strategies for improving access to medicines. We discuss controversial topics, such as pharmaceutical profits and patents, with the goal of building consensus around facts and working towards a solution. We conclude that partnerships and collaboration among multiple stakeholders are urgently needed to improve equitable access to medicines in LMIC.
Pharmaceutical Products; Health Policy; Health Financing; Health Systems
Objective To develop a one week widening access summer school for 16 year old pupils from non-traditional backgrounds who are considering applying to medical school, and to identify its short term impact and key success factors.
Design Action research with partnership schools in deprived inner city areas in five overlapping phases: schools liaison, recruitment of pupils and assessment of needs, programme design, programme delivery, and evaluation. The design phase incorporated findings from one to one interviews with every pupil, and workshops and focus groups for pupils, parents, teachers, medical student assistants, NHS staff, and other stakeholders. An in-depth process evaluation of the summer school was undertaken from the perspective of multiple stakeholders using questionnaires, interviews, focus groups, and observation.
Participants 40 pupils aged 16 years from socioeconomically deprived and under-represented ethnic minority groups.
Results The summer school was popular with pupils, parents, teachers, and staff. It substantially raised pupils' confidence and motivation to apply to medical school. Critical success factors were identified as an atmosphere of “respect”; a focus on hands-on work in small groups; the input of medical students as role models; and vision and leadership from senior staff. A particularly popular and effective aspect of the course was a grand round held on the last day, in which pupils gave group presentations of real cases.
Conclusion An action research format allowed us to draw the different stakeholders into a collaborative endeavour characterised by enthusiasm, interpersonal support, and mutual respect. The input from pupils to the programme design ensured high engagement and low dropout rates. Hands-on activities in small groups and social drama of preparing and giving a grand round presentation were particularly important.
Pharmaceutical representatives provide medicines information on their promoted products to doctors. However, studies have shown that the quality of this information is often low. No study has assessed the medicines information provided by pharmaceutical representatives to doctors in Malaysia and no recent evidence in Australia is present. We aimed to compare the provision of medicines information by pharmaceutical representatives to doctors in Australia and Malaysia.
Following a pharmaceutical representative's visit, general practitioners in Australia and Malaysia who had agreed to participate, were asked to fill out a questionnaire on the main product and claims discussed during the encounter. The questionnaire focused on provision of product information including indications, adverse effects, precautions, contraindications and the provision of information on the Pharmaceutical Benefit Scheme (PBS) listings and restrictions (in Australia only). Descriptive statistics were produced. Chi-square analysis and clustered linear regression were used to assess differences in Australia and Malaysia.
Significantly more approved product information sheets were provided in Malaysia (78%) than in Australia (53%) (P < 0.001). In both countries, general practitioners reported that indications (Australia, 90%, Malaysia, 93%) and dosages (Australia, 76%, Malaysia, 82%) were frequently provided by pharmaceutical representatives. Contraindications, precautions, drug interactions and adverse effects were often omitted in the presentations (range 25% - 41%). General practitioners in Australia and Malaysia indicated that in more than 90% of presentations, pharmaceutical representatives partly or fully answered their questions on contraindications, precautions, drug interactions and adverse effects. More general practitioners in Malaysia (85%) than in Australia (60%) reported that pharmaceutical representatives should have mentioned contraindications, precautions for use, drug interaction or adverse effects spontaneously (P < 0.001). In 48% of the Australian presentations, general practitioners reported the pharmaceutical representatives failed to mention information on PBS listings to general practitioners.
Information on indications and dosages were usually provided by pharmaceutical representatives in Australia and Malaysia. However, risk and harmful effects of medicines were often missing in their presentations. Effective control of medicines information provided by pharmaceutical representatives is needed.
Clinical evidence demonstrates coadministration of tumour necrosis factor inhibitor (TNFi) agents and methotrexate (MTX) is more efficacious than administration of TNFi agents alone in patients with rheumatoid arthritis, leading to the perception that coadministration of MTX with all biologic agents or oral disease-modifying antirheumatic drugs is necessary for maximum efficacy. Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy. Additionally, an analysis of healthcare claims data showed that when MTX was prescribed in conjunction with a biologic agent, as many as 58% of patients did not collect the MTX prescription. Given this discrepancy between perception and real life, we conducted a review of the peer-reviewed literature and rheumatology medical congress abstracts to determine whether data support biologic monotherapy as a treatment option for patients with rheumatoid arthritis. Our analysis suggests only for tocilizumab is there evidence that the efficacy of biologic monotherapy is comparable with combination therapy with MTX.
Rheumatoid Arthritis; Treatment; DMARDs (biologic)
Kenya has experienced a number of retail sector initiatives aimed at improving access to antimalarial medicines. This study explored stakeholders' perceptions of the role of private medicine retailers (PMRs), the value and feasibility of programme goals, perceived programme impact, factors influencing implementation and recommendations in three districts of Kenya.
This study was part of a larger evaluation of PMR programmes, including quantitative and qualitative components. The qualitative research was conducted to assess implementation processes and actors' experiences in the programmes, through focus group discussions with trained PMRs and mothers of children under five years, and in-depth interviews with programme managers, trainers and co-trainers.
PMRs were perceived to provide rapid cheap treatment for non-serious conditions and used as a deliberate and continuously evaluated choice between different treatment sources. All stakeholders supported programme goals and most PMRs described increased customer satisfaction, more rational purchasing of medicine stock and increased medicine sales after participation. Factors undermining programme implementation included a lack of MoH resources to train and monitor large numbers of PMRs, the relative instability of outlets, medicines stocked and retail personnel, the large number of proprietary brands and financial challenges to retailers in stocking antimalarial medicines, and their customers in buying them. Unambiguous national support and a broad range of strategies are important to strengthen the feasibility of change in OTC antimalarial use.
Understanding the context and implementation processes of PMR programmes and the perspectives of key actors are critical to identifying measures to support their effective implementation. Financial barriers underlie many described challenges, with important implications for policies on subsidies in this sector. In spite of barriers to implementation, increased exposure to programme activities promoted trust and improved relationships between PMRs and their clients and trainers, strengthening feasibility of such interventions. Public information can strengthen PMR training programmes by engaging local communities and may facilitate performance monitoring of PMRs by their clients.
Remote access to patient medical records for source data verification is feasible and is potentially an avenue through which resources can be more efficiently used.
With electronic medical records (eMRs), the option now exists for clinical trial monitors to perform source data verification (SDV) remotely. We report on a feasibility study of remote access to eMRs for SDV and the potential advantages of such a process in terms of resource allocation and cost.
The Clinical Trials Unit at the Peter MacCallum Cancer Centre, in collaboration with Novartis Pharmaceuticals Australia, conducted a 6-month feasibility study of remote SDV. A Novartis monitor was granted dedicated software and restricted remote access to the eMR portal of the cancer center, thereby providing an avenue through which perform SDV.
Six monitoring visits were conducted during the study period, four of which were performed remotely. The ability to conduct two thirds of the monitoring visits remotely in this complex phase III study resulted in an overall cost saving to Novartis. Similarly, remote monitoring eased the strain on internal resources, particularly monitoring space and hospital computer terminal access, at the cancer center.
Remote access to patient eMRs for SDV is feasible and is potentially an avenue through which resources can be more efficiently used. Although this feasibility study involved limited numbers, there is no limit to scaling these processes to any number of patients enrolled onto large clinical trials.
Background and Aim
Human and animal studies have clearly established tumor necrosis factor (TNF)α as an important mediator of Crohn’s disease pathogenesis. However, whether systemic or only local TNFα overproduction is required for the development of chronic intestinal inflammation and Crohn’s disease remains unclear. The aim of this study was to assess the contribution of intestinal epithelial-derived TNFα to the development of murine Crohn’s-like ileitis.
We adapted the well-established TNF∆ARE/+ mouse model of Crohn’s disease (which systemically overexpresses TNFα) to generate a homozygous mutant strain that overexpress TNFα only within the intestinal epithelium. Intestinal-specific TNFi∆ARE/i∆ARE mice were examined for histopathological signs of gut inflammation and extraintestinal manifestations of Crohn’s disease. The mucosal immune phenotype was characterized, and the contribution of specific lymphocyte populations to the pathogenesis of TNFi∆ARE/i∆ARE ileitis was assessed.
TNFi∆ARE/i∆ARE mice had increased mucosal and systemic TNFα levels compared to wild-type controls (P<0.001), as well as severe chronic ileitis with increased neutrophil infiltration and villous distortion, but no extraintestinal manifestations (P<0.001 vs. wild-type controls). The gut mucosal lymphocytic compartment was also expanded in TNFi∆ARE/i∆ARE mice (P<0.05), consisting of activated CD69+ and CD4+CD62L- lymphocytes (P<0.05). FasL expression was significantly elevated in the mesenteric lymph nodes of TNFi∆ARE/i∆ARE mice (P<0.05). Adoptive transfer of mucosal TNFi∆ARE/i∆ARE lymphocytes resulted in ileitis in immunologically naïve severe combined immunodeficiency recipients (P<0.05 vs. wild-type controls), indicating an effector phenotype that was associated with increased production of both Th1 (IFNγ) and Th2 (IL-5, IL-13) cytokines.
Intestinal epithelial-derived TNFα is sufficient for the induction of Crohn’s-like ileitis, but not for the occurrence of extraintestinal manifestations, in TNFi∆ARE/i∆ARE mice. These effects were associated with generation of effector lymphocytes within the intestinal mucosa and dysregulated apoptosis. Thus, targeted intestinal blockade of TNFα may provide an effective means to neutralize gut-derived TNFα with reduced side effects.
The majority of retirement village residents are at risk of medication misadventure. In a recent survey of retirement village residents in Victoria, two-thirds had at least one medication-related risk factor, and hence were eligible to receive a government-subsidised Home Medicines Review (HMR). However, only 6% of eligible residents had received a HMR in the previous 12 months. Reasons for the poor uptake of HMR, and interventions for improving HMR uptake, have been identified and developed with input from stakeholders. The trial will test the effect of Pharmacist-conducted HMR to Address the Risk of Medication-related Events in Retirement Villages (PHARMER) in improving the uptake of HMRs among retirement village residents.
This is a multicentre prospective cluster randomised controlled trial. Ten retirement villages in Victoria, Australia will be recruited for this trial. Retirement villages will be selected in consultation with the Residents of Retirement Villages Victoria Inc. (RRVV), based on geographical locations (e.g. northeast or southwest), size and other factors. Residents from selected villages will be recruited with the help of RRVV Resident Liaison Officers using a range of strategies. Randomisation will be by geographical location to minimise contamination. Participating villages and residents will be allocated to either Pharmacist Intervention Group (PIG) or Usual Care Group (UCG). Each group will include five retirement villages and will have at least 77 residents in total. The intervention (PHARMER) comprises educating residents regarding HMR, and using a risk assessment checklist by residents to notify their General Practitioners of their medication risk. Uptake of HMR and medication adherence will be assessed in both PIG and UCG at three and six months using telephone interviews and questionnaires.
This study is the first to develop and test an intervention to improve the uptake of HMR among Australian residents in retirement villages, with a view to decreasing medication risk. A multi-faceted interventional approach will be used as suggested by stakeholders. The trial is expected to be complete by late 2011 and results will be available in 2012.
Australian New Zealand Clinical Trials Registry (ACTRN12611000109909)
Random community genomes (metagenomes) are now commonly used to study microbes in different environments. Over the past few years, the major challenge associated with metagenomics shifted from generating to analyzing sequences. High-throughput, low-cost next-generation sequencing has provided access to metagenomics to a wide range of researchers.
A high-throughput pipeline has been constructed to provide high-performance computing to all researchers interested in using metagenomics. The pipeline produces automated functional assignments of sequences in the metagenome by comparing both protein and nucleotide databases. Phylogenetic and functional summaries of the metagenomes are generated, and tools for comparative metagenomics are incorporated into the standard views. User access is controlled to ensure data privacy, but the collaborative environment underpinning the service provides a framework for sharing datasets between multiple users. In the metagenomics RAST, all users retain full control of their data, and everything is available for download in a variety of formats.
The open-source metagenomics RAST service provides a new paradigm for the annotation and analysis of metagenomes. With built-in support for multiple data sources and a back end that houses abstract data types, the metagenomics RAST is stable, extensible, and freely available to all researchers. This service has removed one of the primary bottlenecks in metagenome sequence analysis – the availability of high-performance computing for annotating the data.
OBJECTIVE: To develop recommendations for office-based physicians who wish to make their offices accessible to all patients. OPTIONS: Include taking steps to make offices more accessible, or not; offices may be accessible to varying degrees. OUTCOMES: Outcomes of accessibility involve patient-care, economic, ethical and legal issues. Stakeholders in these outcomes include patients, physicians, government and society. EVIDENCE: Data were obtained from a series of searches of MEDLINE, CINAHL and Healthstar (previously Health) databases for articles on disability and family medicine, primary (health) care and family practice, and on access and offices, and health services accessibility, and from a telephone survey of 50 stakeholders. VALUES: A high value was placed on services to persons with disabilities and on stakeholder input. Universal accessibility was valued as an overall goal; improved accessibility was also highly valued. BENEFITS, HARMS AND COSTS: Benefits to patients include improved access to care as guaranteed by the Canada Health Act and in keeping with provincial Human Rights Codes. Benefits to physicians include contact with a broader patient population and freedom from fear of litigation. Costs of improved accessibility vary depending on individual circumstances and on whether an office is being built or renovated; some improvement costs are minimal. RECOMMENDATIONS: All physicians should take measures to improve practice accessibility. Improved access should be considered in each of the following areas: transportation and entrance to the facility, entrance to the office, waiting rooms, rest rooms, examination rooms, general building features and other features. VALIDATION: No similar guidelines exist. To assess the content validity of these guidelines, the authors had a draft document reviewed by 18 stakeholders. All specific recommendations met the minimum criterion of adherence to current legislation, including national and provincial building codes. The specific recommendations are endorsed by the Canadian Paraplegic Association (national and Ontario offices), the DisAbled Women's Network (Ontario) and the Centre for Independent Living (Toronto). SPONSORS: Development of these guidelines was supported in part by the Department of Family and Community Medicine, Toronto Hospital, Toronto, Ont.