Generic medicines: Greek physicians' perceptions and prescribing practices

Background and objective:  The penetration of generic drugs in the Greek pharmaceutical market is placed among the weakest in the EU. The Greek regulatory framework does not systematically support the development of this subsector and physicians are not provided with incentives for prescribing generics. The aim of this study was to investigate the prescribing profile of physicians in Greece with a focus on the factors that influence their decision on generics prescribing.
Methods:  A structured questionnaire was sent by mail to a random national sample of 1463 physicians, stratified by sex, specialty and geographical region.
Results and discussion:  The response rate was 82·3%. Greek physicians have a positive view on generics but they prefer to prescribe the original products. According to our analysis, physician's age and their opinion on generics' efficacy and effectiveness are identified as important determinants of their prescribing decision. The primary reason that could make them change their prescribing habits is the appearance of side-effects. Patients' insurance coverage and income, as well as the drug cost are also referred as factors that influence their prescribing decision. Despite the fact that they do not usually prescribe generics in their clinical practice, they are willing to substitute an original drug by a generic product.
Conclusions:  Our findings suggest that Greek physicians could be persuaded to prescribe generic medicines, if a generic promotion policy was introduced in the country. To develop such a policy, a set of supply side and demand-side measures should be implemented along with provision of information on generics to physicians during their education and clinical practice.     

Generics and substitution modalities: proposed methods for the evaluation of equivalence, traceability and pharmacovigilance reporting

The use of generics results in savings for the budget of the health insurance, and no player of health could question seriously the principle. The generic drug of a reference medicinal product defines itself as a drug having the same qualitative and quantitative composition in active ingredients, the same dosage form and the bioequivalence with this reference medicinal product was demonstrated by appropriate studies of bioavailability. It is the right to switch granted to the pharmacists in 1999 that is at the origin of the real development of these specialties on the French pharmaceutical market. Nevertheless, about 10 years later, it seems that the system in place does not offer all the necessary securities with regard to pharmacovigilance, notably for the products with narrow therapeutic margin. By strengthening and/or by completing the role played by the health care professionals and the public institutions concerned, it is highly possible to improve the robustness of the system. Also, the recent arrival in Europe of the biosimilars, similar molecules but not bioequivalent to biological products, cause an even more tricky specific situation than that of the generics because of their nature, of the difficulty to manufacture them, and of the risk of immunogenicity. If the substitution is not permitted in several European countries including France, the other issues can appear especially in case of interchangeability requiring also, the reinforcement of certain measures.The various aspects are described in this article with concrete proposals on how the current system can be made safer, both for the generics and the biosimilars.     

Case reports of the reemergence of psychotic symptoms after conversion from brand-name clozapine to a generic formulation.

BACKGROUND: The use of generic drugs has resulted in considerable cost savings; however, whether all generics are truly bioequivalent to their brand-name counterparts is questionable. Although the efficacy of clozapine in the management of treatment-resistant schizophrenia has been well established, reports of relapse after conversion to a generic formulation are becoming more common. OBJECTIVE: This article presents 7 case studies of patients in a long-term residential care facility who experienced a relapse of psychotic symptoms when the pharmacy inadvertently switched their therapy from brand-name clozapine to a generic formulation. Neither patients, physicians, nor staff of the facility were aware of this switch. Possible reasons for the apparent increased risk of relapse in some patients switched to the generic formulation of clozapine are explored, with reference to US Food and Drug Administration bioequivalence standards and reports. RESULTS: All 7 patients, whose condition had been well stabilized with brand-name clozapine, experienced a rapid and profound deterioration after the switch to the generic formulation. Five patients required hospitalization. All patients responded well when brand-name clozapine was reinstated. CONCLUSION: The findings suggest that brand-name clozapine and the generic formulation may display important clinical differences, and a comparable therapeutic response may not be achievable despite adequate monitoring. Large, controlled, prospective trials are needed to clarify the potential for treatment failure with the use of generic clozapine.     

How practitioners view generic drugs: an opinion study from general practitioners in Maine-et-Loire (France)

INTRODUCTION: Generic drugs are copies of original drugs, hence their low cost. In France, expansion of the use of generic drugs is not significant and the support of practitioners is essential in increasing this. AIM: The purpose of this study was to survey the opinion and practical experience of physicians regarding generic drugs, in order to develop a proposal for the safer use of these drugs. METHODS: A form was sent to the 1235 general and specialist practitioners in the Maine-et-Loire "département" with assistance from the regional health insurance, in March 2002. The main topics studied were prescribing practices, risks associated with generic drugs and pharmacist substitutions. The chi2 test and Fisher's exact test were used in the data analysis. RESULTS: Four hundred and twenty-nine forms were returned (34.7%). Only 55% of practitioners considered generic drugs to be as safe and effective as original drugs. Fifty-nine percent prescribe generics rarely or never. The prescribing depends on many factors, linked to the practitioner, the patient or the drug. Many practitioners reported adverse events with generic medicines. With regard to the switch by the pharmacist, it was reported that 45% of prescribers would refuse it in some instances. Among the proposals, cooperation between practitioners and pharmacists in the choice of the generic drugs was approved by 57% of physicians. DISCUSSION: The main perception is that the vastness of the generic world and the fear of adverse events are somewhat bewildering for both patients and health professionals. Among the proposals made by practitioners, a decrease in the number of generics for a same molecule and the institution of a standard price are widely approved. CONCLUSION: Practitioners do not refuse to use generic drugs but are very concerned about the risks of adverse effects for their patients. They regard it as important that a patient receiving chronic treatment be given the same generic drug each time.     

Even Apparently Insignificant Chemical Deviations among Bioequivalent Generic Antibiotics Can Lead to Therapeutic Nonequivalence: the Case of Meropenem

Several studies with animal models have demonstrated that bioequivalence of generic products of antibiotics like vancomycin, as currently defined, do not guarantee therapeutic equivalence. However, the amounts and characteristics of impurities and degradation products in these formulations do not violate the requirements of the U.S. Pharmacopeia (USP). Here, we provide experimental data with three generic products of meropenem that help in understanding how these apparently insignificant chemical differences affect the in vivo efficacy. Meropenem generics were compared with the innovator in vitro by microbiological assay, susceptibility testing, and liquid chromatography/mass spectrometry (LC/MS) analysis and in vivo with the neutropenic guinea pig soleus infection model (Pseudomonas aeruginosa) and the neutropenic mouse thigh (P. aeruginosa), brain (P. aeruginosa), and lung (Klebisella pneumoniae) infection models, adding the dihydropeptidase I (DHP-I) inhibitor cilastatin in different proportions to the carbapenem. We found that the concentration and potency of the active pharmaceutical ingredient, in vitro susceptibility testing, and mouse pharmacokinetics were identical for all products; however, two generics differed significantly from the innovator in the guinea pig and mouse models, while the third generic was therapeutically equivalent under all conditions. Trisodium adducts in a bioequivalent generic made it more susceptible to DHP-I hydrolysis and less stable at room temperature, explaining its therapeutic nonequivalence. We conclude that the therapeutic nonequivalence of generic products of meropenem is due to greater susceptibility to DHP-I hydrolysis. These failing generics are compliant with USP requirements and would remain undetectable under current regulations.     

Conference report: International Haemovigilance Seminar and the SHOT Annual Symposium, 10–12 July 2018

The Annual SHOT Report was published on July 12 at the Annual Symposium. This was preceded by a 2‐day meeting of the International Haemovigilance Network (IHN). The IHN meeting provides an opportunity for haemovigilance experts to network with one another and share presentations, which this year included those from China and Taiwan. Reviews of pulmonary complications were highlighted since the definitions of both transfusion‐related acute lung injury and transfusion‐associated circulatory overload are undergoing revision. The seminar provided an opportunity to present some UK data to an international group (the INTERVAL donor study, the value of big data and work on genomics and human factors). SHOT reports for incidents reported in 2017 demonstrate that, overall, 85·5% are caused by errors. Key recommendations from SHOT are: (i) All staff involved in transfusion must be trained in and know ABO group compatibility. Clinical staff must not just rely on the laboratory staff to get this right. (ii) IT systems have the potential to increase transfusion safety by minimising human factors and should be considered for all transfusion steps. (iii) A formal risk assessment for transfusion‐associated circulatory overload should be undertaken wherever possible.     

Protocolized weaning from mechanical ventilation: ICU physicians' views

BACKGROUND: The use of protocols during weaning from mechanical ventilation is uncommon in the UK, despite research pointing to their potential benefits. This may be because the research evidence is considered not to apply in different settings. Intensive care unit consultant physicians are the major decision-makers in weaning in the UK and any attempt to introduce protocolized weaning will require consideration of their views. AIM: The aim of this paper is to report a study exploring intensive care physicians' views on (i) weaning from mechanical ventilation, (ii) the utility of weaning protocols and (iii) nurses' roles in the weaning process. A specific goal was to identify potential aids and barriers to developing weaning protocols and their introduction into clinical practice. METHODS: Qualitative interviews were conducted with a purposive sample of 10 consultant physicians in two intensive care units in Northern Ireland and subjected to content analysis. FINDINGS: The primary themes identified were (i) information required for weaning decisions and clinical judgement, (ii) professional boundaries, (iii) protocol issues and (iv) timing of weaning. Three types of information were deemed to be required for weaning decisions - empirical objective, empirical subjective and abstract - and interviewees considered that it would be challenging to incorporate all into a protocol. They were divided on whether protocols were useful when nursing experience was limited. Some groups of patients were thought more suitable than others for protocolized weaning. CONCLUSIONS: Although local physicians were supportive in theory, introduction of protocolized weaning is likely to be difficult because of the breadth of information required for successful decision-making. Consultant views in this study were not consistent with American findings that physicians' caution may unnecessarily prolong weaning.     

Bioequivalence and other unresolved issues in generic drug substitution

BACKGROUND: Substitution of generic drugs for brand-name products is highly controversial and often is met with suspicion by health care providers and patients. Historically, the debate has focused on the issue of bioequivalence, and clinical practice has identified a number of drug classes for which generic substitution should be approached with caution. Current bioequivalence requirements are based on a measure of average bioequivalence; however, there are fears that use of this measure may be inappropriate in the case of a drug with a narrow or wide therapeutic range or high intrasubject or intersubject variability. Under these circumstances, measures of individual and population bioequivalence are proposed to be more accurate than measures of average bioequivalence. OBJECTIVE: This paper addresses issues of bioequivalence and other concerns with generic drug substitution. METHODS: I conducted a MEDLINE search of the English-language literature containing the key terms generic, multisource, quality, and brand and published between 1973 and 2003. The names of branded pharmaceuticals whose patents had recently expired (eg, Ventolin HFA, Adalat, Capoten, Tagamet HB 200, and Valium) also were used to search for articles on generic substitution. Reference lists of relevant articles also were searched. Bioequivalence issues are presented together with more general concerns over generic drug substitution, such as consumer perception of risk, differences in product and packaging appearance, and differences in excipients. RESULTS: The literature reviewed act to highlight a number of different drug categories and patient subpopulations for which generic substitution can still prove to be problematic. CONCLUSION: I recommend that health care providers continue to exercise caution in the consideration of generic drug substitution under certain circumstances.     

Proton pump inhibitors prescribing following the introduction of generic drugs

Eur J Clin Invest 2012; 42 (10): 1068-1078 ABSTRACT: Background In many countries, the introduction of generic proton pump inhibitors (PPIs) onto the pharmaceutical market increased the phenomenon of therapeutic substitution in acid-related disorders (ARDs). Aim To investigate the treatment of ARDs in an Italian primary care setting from 2005 to 2008 by verifying: (i) dynamics of PPI prescribing; (ii) predictors of PPI switching; and (iii) healthcare resource consumption costs. Methods This was a retrospective cohort study of 102 general practitioners (GPs) who managed an average of 150?000 inhabitants in Naples. Multilevel logistic regression was used to assess the potential predictors of both PPI switching and termination. Primary care costs were expressed as the cost of ARD management per PPI user year. Results The percentage of PPI users with ARD increased from 5·5% (2005) to 7·0% (2008) (P?相似文献   

Risk perception for developing diabetes: comparative risk judgments of physicians

OBJECTIVE: To assess personal risk perceptions for developing diabetes among practicing physicians. RESEARCH DESIGN AND METHODS: Little is known about comparative risk perceptions concerning diabetes among medical experts. We administered the new Risk Perception Survey for Developing Diabetes to 535 nondiabetic physicians. The participants were 86% male, had a mean age of 49 years, and were 66% white and 24% Asian. Almost 37% were considered at higher risk for developing diabetes based on self-reported risk factors. Over 91% of respondents were either internal medicine or family medicine physicians. RESULTS: Of the four subscales, Comparative Disease Risk and Environmental Risk indicated moderate risk perceptions, whereas Personal Control scores indicated a robust sense of control over developing diabetes. Optimistic Bias scores showed a tendency toward participants' being optimistic that they were less likely to develop diabetes. Based on self-reported risk factor categories, a comparison of scores between physicians at higher risk (n = 196) and those at lower risk (n = 313) for developing diabetes showed greater comparative disease risk perception among the higher risk physicians (P < 0.01), as well as greater perception of diabetes risk (P < 0.001). Nearly 50% of higher risk physicians, however, reported an optimistic bias that they were less likely to develop diabetes than other people of their same age and sex. Women (n = 75) reported greater perception of environmental risks than men (P < 0.001). Asian respondents (n = 126) reported greater perception of environmental risk (P < 0.001) and greater worry about developing diabetes (P < 0.0001) than white respondents (n = 355). Regression analyses showed that scores for nondiabetes comparative disease risks (0.39) and level of optimistic bias (0.31) were predictive of diabetes risk perception (P < 0.0001). CONCLUSIONS: The data gathered on physicians' perception of their personal risk for developing diabetes and other comparative risk judgments provided an expert comparison for future analyses of at-risk or lay individuals' perceptions of diabetes risk. Effective communication of diabetes risk among physicians, patients, and the general public relies on knowledge of and sensitivity to group differences in these perceptions.     

Benefits and adverse effects associated with yoga practice: A cross-sectional survey from India

ObjectiveBenefits and adverse effects of yoga were reported in surveys from different countries. The present study aimed to (i) determine the benefits and adverse effects of yoga in yoga experienced persons in India and (ii) correlate these effects of yoga with factors related to the individual and their yoga practice.Design and settingThis convenience sampling in-person survey reports benefits and adverse effects of yoga in 3135 yoga experienced persons.ResultsThe benefits of yoga were reported by 94.5 percent of the respondents. The three most common benefits were improvement in: (i) physical fitness, (ii) mental state and (iii) cognitive functions. An adverse effect of yoga was reported by 1.9 percent of the respondents. The three most common adverse effects reported were: (i) soreness and pain, (ii) muscle injuries and (iii) fatigue. The following factors showed a significant association (in all cases p < 0.05 Chi square test; Cramer’s V > 0.10) with reported benefits of yoga: (i) experience of yoga in months, (ii) time spent practicing yoga in a week, (iii) number of yoga techniques practiced, and (iv) whether awareness was maintained during the yoga practice or not.ConclusionBenefits of yoga practice to physical health were the most common, with soreness and pain the most common adverse effect of yoga. Yoga practice related factors influence the benefits of yoga.     

Obtaining access to data sources: an exploration of method, problems and possible solutions

A method, route and problems relating to the gaining of access to research data or respondents in discussed. In seeking permission to gather data from patients and staff in Scottish psychiatric hospitals, using Flanagan's Critical Incident Technique, a number of problems were encountered, viz. (i) the varying administrative levels to which the first formal request for entry had to be made; (ii) the varying routes which had to be followed in order to gain permission, and (iii) the time taken to obtain access to data sources. The problems, their possible consequences, and a number of long and short term recommendations are made. If implemented, these may go some way toward minimizing the difficulties associated with gaining access to data sources. The long term recommendations, including improved nurse representation on existing research and ethical committees, are directed to those who shape and influence policies relating to research practice generally. The short term recommendations are directed to the nurse researcher who is seeking access to field sites, with a view to minimizing problems relating to this aspect of planning and carrying out research activity.     

Mental health nurses’ views of recovery within an acute setting

How the principles of a recovery‐oriented mental health service are incorporated in the day‐to‐day nursing practice of mental health nurses in inpatient settings is unclear. In this study, we interviewed 21 mental health nurses working in acute inpatient mental health units about a range of recovery‐focused topics. Three overlapping themes were identified: (i) the perception of recovery; (ii) congruent humanistic approaches; and (iii) practical realities. Only four interviewees had some formal training about recovery. Most respondents recognize that positive attitudes, person‐centred care, hope, education about mental illness, medication and side‐effects, and the acknowledgement of individual recovery pathways are necessary to prevent readmission, and are central to a better life for people who live with a mental illness. This research supports the view that ideas and practices associated with the recovery movement have been adopted to some degree by nurses working at the acute end of the services continuum. However, most saw the recovery orientation as rhetoric rather than as an appropriately resourced, coordinated, and integrated program. These nurses, however, speak of much more detailed aspects of working with patients and being required to prepare them for the exigencies of living in the community post‐discharge.     

Prescribability and switchability of highly variable drugs and drug products.

At the AAPS/FDS Workshop (Crystal City, Arlington, VA, March 6-8, 1995), it was agreed that some form of scaling should be permitted for highly variable drugs, although there was no agreement on a method. Currently, much emphasis is focused on developing a practical methodology for individual bioequivalence (IBE) and population bioequivalence (PBE) to replace or complement average bioequivalence (ABE). The latter requires only the mean bioavailabilities of two formulations to be sufficiently similar, whereas PBE also considers their distributions. IBE, on the other hand, is a comparison of the individual responses to the two formulations within subjects and is therefore concerned with switchability (interchangeability) between two multisource formulations. Multisource formulations refer (i) to generic copies of an innovator's formulation or (ii) to different formulations used in stages leading up to the final marked formulation. Evaluation of both PBE and IBE require replicate design studies. The FDA Working Group on IBE has been experimenting with methods in which a one-sided 95% confidence interval is computed based on the Bootstrap technique which ensures that the consumer risk is maintained at 5%. The IBE metric can then be scaled according to the within subject variance of the reference formulation. Thus if the variability of the test formulation (T) is higher than that of the reference (R), the formulation may fail IBE but not ABE. Conversely, if R is more variable than T, then the formulations may be considered to be IBE, even with a difference in means of more than 20%. Experimentation with existing data on our files shows that scaling has a considerable effect on the IBE decision for highly variable drugs. Evidence will also be presented to show that scaling makes the conditions more conservative for potent drugs with steep dose response curves reducing the risk of two generic formulations being BE with the same reference product but not BE with each other. On the other hand, broadening the BE limits for safe, highly variable drugs increases statistical power and reduces the number of subjects required. Even with the introduction of scaling, however, it is clearly difficult to obtain a single IBE criterion suitable to be applied to all drug products/studies.     

Effects of Cytochalasin B on the Intracellular Bactericidal Activity of Human Neutrophils

Cytochalasin B (CB) is known to have some inhibitory effects on cytokinesis, single-cell movement, bacterial uptake by phagocytes, and many other processes. The effects of CB on intraleukocytic bactericidal activities in human leukocytes were studied, and the results were summarized as follows. (i) CB inhibited the early stage of the intracellular bactericidal activity of human leukocytes against Streptococcus pyogenes D58 (group A). The effect was rapidly eliminated by rinsing the CB solution. (ii) In the late stage of the intracellular bactericidal process, however, CB possessed no effect against S. pyogenes D58 (group A) and Staphylococcus aureus 209P. (iii) CB also inhibited the translocation of myeloperoxidase granules to the phagosomes of human neutrophils.