No difference in between-country variability in use of newly approved orphan and non- orphan medicinal products - a pilot study

<p>Abstract</p> <p>Background</p> <p>Regulators and payers have to strike a balance between the needs of the patient and the optimal allocation of resources. Drugs indicated for rare diseases (orphan medicines) are a special group in this context because of their often high per unit costs. Our objective in this pilot study was to determine, for drugs used in an outpatient setting, how utilisation of centrally authorised drugs varies between countries across a selection of EU member states.</p> <p>Methods</p> <p>We randomly selected five orphan medicines and nine other drugs that were centrally authorised in the European Union between January 2000 and November 2006. We compared utilisation of these drugs in six European Union member states: Austria, Denmark, Finland, Portugal, The Netherlands, and Sweden. Utilisation data were expressed as Defined Daily Doses per 1000 persons per year. Variability in use across countries was determined by calculating the relative standard deviation for the utilisation rates of individual drugs across countries.</p> <p>Results</p> <p>No association between orphan medicine status and variability in use across countries was found (P = 0.52). Drugs with an orphan medicine status were more expensive and had a higher innovation score than drugs without an orphan medicine status.</p> <p>Conclusions</p> <p>The results show that the variability in use of orphan medicines in the different health care systems of the European Union appears to be comparable to the other newly authorised drugs that were included in the analysis. This means that, although strong heterogeneity in access may exist, this heterogeneity is not specific for drugs with an orphan status.</p

National medicines policies – a review of the evolution and development processes

OBJECTIVES: Continuous provision of appropriate medicines of assured quality, in adequate quantities, and at reasonable prices is a concern for all national governments. A national medicines policy (NMP) developed in a collaborative fashion identifies strategies needed to meet these objectives and provides a comprehensive framework to develop all components of a national pharmaceutical sector. To meet the health needs of the population, there is a general need for medicine policies based on universal principles, but nevertheless adapted to the national situation. This review aims to provide a quantitative and qualitative (describing the historical development) study of the development process and evolution of NMPs. METHODS: The number of NMPs and their current status has been obtained from the results of the assessment of WHO Level I indicators. The policy formulation process is examined in more detail with case studies from four countries: Sri Lanka, Australia, former Yugoslav Republic of Macedonia and South Africa. RESULTS: The number of NMPs worldwide has increased in the last 25 years with the highest proportional increase in the last 5–10 years in high-income countries. Higher income countries seem to have more NMP implementation plans available and have updated their NMP more recently. The four case studies show that the development of a NMP is a complex process that is country specific. In addition, it demonstrates that an appropriate political window is needed for the policy to be passed (for South Africa and the FYR Macedonia, a major political event acted as a trigger for initiating the policy development). Policy-making does not stop with the official adoption of a policy but should create mechanisms for implementation and monitoring. The NMPs of the FYR Macedonia and Australia provide indicators for monitoring. CONCLUSIONS: To date, not all countries have a NMP since political pressure by national experts or non-governmental organizations is generally needed to establish a NMP. Case studies in four countries showed that the policy process is just as important as the policy document since the process must create a mechanism by which all stakeholders are brought together and a sense of collective ownership of the final policy may be achieved

Testing bias in clinical databases: methodological considerations

<p>Abstract</p> <p>Background</p> <p>Laboratory testing in clinical practice is never a random process. In this study we evaluated testing bias for neutrophil counts in clinical practice by using results from requested and non-requested hematological blood tests.</p> <p>Methods</p> <p>This study was conducted using data from the Utrecht Patient Oriented Database. This clinical database is unique, as it contains physician requested data, but also data that are not requested by the physician, but measured as result of requesting other hematological parameters. We identified adult patients, hospitalized in 2005 with at least two blood tests during admission, where requests for general blood profiles and specifically for neutrophil counts were contrasted in scenario analyses. Possible effect modifiers were diagnosis and glucocorticoid use.</p> <p>Results</p> <p>A total of 567 patients with requested neutrophil counts and 1,439 patients with non-requested neutrophil counts were analyzed. The absolute neutrophil count at admission differed with a mean of 7.4 × 10⁹/l for requested counts and 8.3 × 10⁹/l for non-requested counts (p-value < 0.001). This difference could be explained for 83.2% by the occurrence of cardiovascular disease as underlying disease and for 4.5% by glucocorticoid use.</p> <p>Conclusion</p> <p>Requests for neutrophil counts in clinical databases are associated with underlying disease and with cardiovascular disease in particular. The results from our study show the importance of evaluating testing bias in epidemiological studies obtaining data from clinical databases.</p

Effect of the economic recession on pharmaceutical policy and medicine sales in eight European countries

Abstract Objective: To identify pharmaceutical policy changes during the economic recession in eight European countries and to determine whether policy measures resulted in lower sales of, and less expenditure on, pharmaceuticals. Methods: Information on pharmaceutical policy changes between 2008 and 2011 in eight European countries was obtained from publications and pharmaceutical policy databases. Data on the volume and value of the quarterly sales of products between 2006 and 2011 in the 10 highest-selling therapeutic classes in each country were obtained from a pharmaceutical market research database. We compared these indicators in economically stable countries; Austria, Estonia and Finland, to those in economically less stable countries, Greece, Ireland, Portugal, Slovakia and Spain. Findings: Economically stable countries implemented two to seven policy changes each, whereas less stable countries implemented 10 to 22 each. Of the 88 policy changes identified, 33 occurred in 2010 and 40 in 2011. They involved changing out-of-pocket payments for patients in 16 cases, price mark-up schemes in 13 and price cuts in 11. Sales volumes increased moderately in all countries except Greece and Portugal, which experienced slight declines after 2009. Sales values decreased in both groups of countries, but fell more in less stable countries. Conclusion: Less economically stable countries implemented more pharmaceutical policy changes during the recession than economically stable countries. Unexpectedly, pharmaceutical sales volumes increased in almost all countries, whereas sales values declined, especially in less stable countries

Is new drug prescribing in primary care specialist induced?

<p>Abstract</p> <p>Background</p> <p>Medical specialists are often seen as the first prescribers of new drugs. However, the extent to which specialists influence new drug prescribing in primary care is largely unknown.</p> <p>Methods</p> <p>This study estimates the influence of medical specialists on new drug prescribing in primary care shortly after market introduction. The influence of medical specialists on prescribing of five new drugs was measured in a cohort of 103 GPs, working in 59 practices, over the period 1999 until 2003. The influence of medical specialists on new drug prescribing in primary care was assessed using three outcome measures. Firstly, the proportion of patients receiving their first prescription for a new or reference drug from a specialist. Secondly, the proportion of GPs prescribing new drugs before any specialist prescribes to their patients. Thirdly, we compared the time until the GP's first own prescribing between GPs who waited for prescriptions from specialists and those who did not.</p> <p>Results</p> <p>The influence of specialists showed considerable differences among the new drugs studied. The proportion of patients receiving their first prescription from a specialist was greatest for the combination salmeterol/fluticasone (60.2%), and lowest for rofecoxib (23.0%). The proportion of GPs prescribing new drugs before waiting for prescriptions from medical specialists ranged from 21.1% in the case of esomeprazole to 32.9% for rofecoxib. Prescribing new drugs by specialists did not shorten the GP's own time to prescribing.</p> <p>Conclusion</p> <p>This study shows that the influence of medical specialists is clearly visible for all new drugs and often greater than for the existing older drugs, but the rapid uptake of new drugs in primary care does not seem specialist induced in all cases. GPs are responsible for a substantial amount of all early prescriptions for new drugs and for a subpopulation specialist endorsement is not a requisite to initiate in new drug prescribing. This contradicts with the idea that the diffusion of newly marketed drugs always follows a two-step model, with medical specialists as the innovators and GPs as the followers.</p

Distinguishing patterns in the dynamics of long-term medication use by Markov analysis: beyond persistence

<p>Abstract</p> <p>Background</p> <p>In order to accurately distinguish gaps of varying length in drug treatment for chronic conditions from discontinuation without resuming therapy, short-term observation does not suffice. Thus, the use of inhalation corticosteroids (ICS) in the long-term, during a ten-year period is investigated. To describe medication use as a continuum, taking into account the timeliness and consistency of refilling, a Markov model is proposed.</p> <p>Methods</p> <p>Patients, that filled at least one prescription in 1993, were selected from the PHARMO medical record linkage system (RLS) containing >95% prescription dispensings per patient originating from community pharmacy records of 6 medium-sized cities in the Netherlands.</p> <p>The probabilities of continuous use, the refilling of at least one ICS prescription in each year of follow-up, and medication free periods were assessed by Markov analysis. Stratified analysis according to new use was performed.</p> <p>Results</p> <p>The transition probabilities of the refilling of at least one ICS prescription in the subsequent year of follow-up, were assessed for each year of follow-up and for the total study period.</p> <p>The change of transition probabilities in time was evaluated, e.g. the probability of continuing ICS use of starters in the first two years (51%) of follow-up increased to more than 70% in the following years. The probabilities of different patterns of medication use were assessed: continuous use (7.7%), cumulative medication gaps (1–8 years 69.1%) and discontinuing (23.2%) during ten-year follow-up for new users. New users had lower probability of continuous use (7.7%) and more variability in ICS refill patterns than previous users (56%).</p> <p>Conclusion</p> <p>In addition to well-established methods in epidemiology to ascertain compliance and persistence, a Markov model could be useful to further specify the variety of possible patterns of medication use within the continuum of adherence. This Markov model describes variation in behaviour and patterns of ICS use and could also be useful to investigate continuous use of other drugs applied in chronic diseases.</p

Mapping the risk of infections in patients with multiple sclerosis: A multi-database study in the United Kingdom Clinical Practice Research Datalink GOLD and Aurum

BACKGROUND: People with multiple sclerosis (pwMS) have an increased risk of infections; risk factors include underlying disease, physical impairment and use of some disease-modifying treatments. OBJECTIVE: To quantify changes in population-level infection rates among pwMS and compare these to the general population and people with rheumatoid arthritis (pwRA), and identify patient characteristics predictive of infections after MS diagnosis. METHODS: We conducted a multi-database study using data on 23,226 people with MS diagnosis from the UK Clinical Practice Research Datalink Aurum and GOLD (January 2000-December 2020). PwMS were matched to MS-free controls and pwRA. We calculated infection rates, and estimated incidence rate ratios (IRR) and 95% confidence intervals (CI) of predictors for infections ⩽ 5 years after MS diagnosis using Poisson regression. RESULTS: Among pwMS, overall infection rates remained stable - 1.51-fold (1.49-1.52) that in MS-free controls and 0.87-fold (0.86-0.88) that in pwRA - although urinary tract infection rate per 1000 person-years increased from 98.7 (96.1-101) (2000-2010) to 136 (134-138) (2011-2020). Recent infection before MS diagnosis was most predictive of infections (1 infection: IRR 1.92 (1.86-1.97); ⩾2 infections: IRR 3.00 (2.89-3.10)). CONCLUSION: The population-level elevated risk of infection among pwMS has remained stable despite the introduction of disease-modifying treatments

Prior outpatient antibiotic use as predictor for microbial aetiology of community-acquired pneumonia: hospital-based study

Objective: The causative micro-organism in community-acquired pneumonia (CAP) is often difficult to predict. Different studies have examined chronic morbidity and clinical symptoms as predictors for microbial aetiology of pneumonia. The aim of our study was to assess whether prior outpatient antimicrobial treatment is predictive for determining the microbial aetiology of CAP. Methods: This was a hospital-based prospective observational study including all patients admitted with CAP between 1 October 2004 and 1 August 2006. Microbial investigations included sputum, blood culture, sputum PCR, antigen testing and serology. Exposure to antimicrobial drugs prior to hospital admission was ascertained through community pharmacy dispensing records. Multivariate logistic regression analysis was conducted to assess whether prior outpatient antimicrobial treatment is a predictor of microbial aetiology. Patient demographics, co-morbidities and pneumonia severity were considered to be other potential predictors. Results: Overall, 201 patients were included in the study. The microbial aetiology was determined in 64% of the patients. The five most prevalent pathogens were Streptococcus pneumoniae, Heamophilus influenzae, Legionella spp., Mycoplasma pneumoniae and Influenza virus A+B. Forty-seven of the patients (23%) had received initial antimicrobial treatment as outpatients. Multivariate analyses revealed that initial outpatient beta-lactam treatment was associated with a threefold increased chance of finding atypical pathogens and a threefold decreased probability of pneumococcal infection; the corresponding odds ratios were 3.51 (95% CI 1.25-9.99) and 0.30 (95% CI 0.10-0.90), respectively. Patients who received macrolides prior to hospitalisation had an increased probability of viral pneumonia. Conclusion: Prior outpatient antimicrobial therapy has a predictive value in the diagnostic workup aimed at identifying the causative pathogen and planning corresponding antimicrobial treatment in patients hospitalised for pneumonia

Prescription of respiratory medication without an asthma diagnosis in children: a population based study

Background. In pre-school children a diagnosis of asthma is not easily made and only a minority of wheezing children will develop persistent atopic asthma. According to the general consensus a diagnosis of asthma becomes more certain with increasing age. Therefore the congruence between asthma medication use and doctor-diagnosed asthma is expected to increase with age. The aim of this study is to evaluate the relationship between prescribing of asthma medication and doctor-diagnosed asthma in children age 0-17. Methods. We studied all 74,580 children below 18 years of age, belonging to 95 GP practices within the second Dutch national survey of general practice (DNSGP-2), in which GPs registered all physician-patient contacts during the year 2001. Status on prescribing of asthma medication (at least one prescription for beta2-agonists, inhaled corticosteroids, cromones or montelukast) and doctor-diagnosed asthma (coded according to the International Classification of Primary Care) was determined. Results. In total 7.5% of children received asthma medication and 4.1% had a diagnosis of asthma. Only 49% of all children receiving asthma medication was diagnosed as an asthmatic. Subgroup analyses on age, gender and therapy groups showed that the Positive Predictive Value (PPV) differs significantly between therapy groups only. The likelihood of having doctor-diagnosed asthma increased when a child received combination therapy of short acting beta2-agonists and inhaled corticosteroids (PPV = 0.64) and with the number of prescriptions (3 prescriptions or more, PPV = 0.66). Both prescribing of asthma medication and doctor-diagnosed asthma declined with age but the congruence between the two measures did not increase with age. Conclusion. In this study, less than half of all children receiving asthma medication had a registered diagnosis of asthma. Detailed subgroup analyses show that a diagnosis of asthma was present in at most 66%, even in groups of children treated intensively with asthma medication. Although age strongly influences the chance of being treated, remarkably, the congruence between prescribing of asthma medication and doctor-diagnosed asthma does not increase with age