Attitudes of Slovene general practitioners towards generic drug prescribing and comparison with international studies

BACKGROUND: Over the recent years there has been a steady 7% yearly increase in prescribing costs, which accounts for 17% of the Slovene national health care budget. Substitution of branded products by generic equivalents can offer savings. General practitioners (GPs) are often concerned about the quality of generic products and possible legal liabilities associated with their use. OBJECTIVE: We wanted to examine the attitudes of GPs in Slovenia towards generic drug prescribing. METHODS: We conducted a postal survey of a random sample of 200 out of 800 GPs in Slovenia from the National Health Insurance Institute database. GPs were asked 21 questions regarding their knowledge on generic drugs, awareness of prescribing costs, prices of generic drugs relative to brand name drugs and their attitude towards use of generic drugs. RESULTS: The 117 (58.5%) replies we received represent 15% of the GP population in Slovenia. 66.1% of GPs considered rising costs of medicines to be a serious problem for the health care budget. Each week, over 50% of GPs experienced demands from patients for specific drugs and the majority of GPs usually met their patients' demands or requests from hospital consultants for branded products. 38.3% of GPs did not take price into consideration when prescribing drugs. The majority of GPs (88.9%) perceived generics to have the same effectiveness as branded drugs. One quarter of GPs would prescribe more generics if additional clinical trials were presented. 37.3% would follow advice of academic detailers and 30.3% expected the generics to be even cheaper than they were. Independent detailing was welcomed by 63.8% of GPs because of the big influence of the pharmaceutical industry on the prescribing habits. 15.5% thought that the industry had a tremendous impact on their prescribing patterns. CONCLUSIONS: Slovene GPs are aware of the cost of prescribed drugs. They are willing to accept independent academic detailing to improve their prescribing and are willing to increase generic drugs under certain conditions.     

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.     

Generic substitution of antihypertensive drugs: does it affect adherence?

BACKGROUND: Generic substitution is an important opportunity to reduce the costs of pharmaceutical care. However, pharmacists and physicians often find that patients and brand-name manufacturers have doubt about the equivalence of the substituted drug. This may be reflected by decreased adherence to therapy. OBJECTIVE: To assess the association between generic substitution and nonadherence to antihypertensive drugs. METHODS: We conducted a matched cohort study between January 1, 1999, and December 31, 2002. Data were obtained from PHARMO, a record linkage system containing drug-dispensing records from community pharmacies and linked hospital discharge records of approximately 950,000 people in The Netherlands. Residents of 30 medium-sized cities who initiated antihypertensive drug therapy were potential subjects. Refill adherence with antihypertensive drugs after substitution was determined; those with refill adherence below 80% were considered nonadherent. RESULTS: Four hundred sixty-three patients with a substitution in therapy and 565 controls, matched on age, gender, therapy start date, duration of use, and generic product code, were identified. Of the patients who switched from brand-name to generic formulations ("substituted"), 13.6% were nonadherent, and of the non-substituted patients (those who did not switch to generic), 18.7% were nonadherent (OR 0.68; 95% CI 0.48 to 0.96). The association was absent in males. None of the patients discontinued the medication. No differences in hospitalizations for cardiovascular disease in the 6 months after the substitution were observed. CONCLUSIONS: Generic substitution of antihypertensive drugs does not lead to lower adherence or more discontinuation and cardiovascular disease-related hospitalizations compared with brand-name therapy. When a less-expensive antihypertensive generic equivalent becomes available, generic substitution should be considered to achieve economic benefits.     

Influence of socioeconomic status on drug selection for the elderly in Canada

OBJECTIVE: To examine the association between socioeconomic status, as indicated by neighborhood median income levels, and physician drug selection between older, less expensive generic drugs and newer, more expensive brand-name drugs for elderly patients initiating drug therapy in a universal healthcare system. METHODS: We conducted a population-based, retrospective, cross-sectional study. Using healthcare administrative databases, we assessed the medication profiles of 128 314 patients from more than 1.4 million residents of Ontario > or =65 years old initiating antipsychotic, hydroxymethylglutaryl-coenzyme A reductase inhibitor (statin), or ocular beta-blocker drug therapy from January 1, 1998, through December 31, 1999. We examined the selection of older generic drugs relative to newer brand-name agents for patients in each of 5 income quintiles. RESULTS: Overall, brand-name drug prescribing modestly increased with increasing income quintile after adjusting for patient age and gender (61.2% in the lowest income quintile vs. 64.1% in the highest income quintile; p value for trend < 0.001). Significant risk ratios comparing the highest with the lowest income-quintile patients were observed for selection of newer, brand-name antipsychotics (RR 1.14; 95% CI 1.06 to 1.23), older generic statins (RR 0.86; 95% CI 0.77 to 0.95), and newer, brand-name ocular beta-blockers (RR 1.13; 95% CI 1.02 to 1.25). CONCLUSIONS: This study suggests that income-related differences in treatment selection by physicians may exist. The reasons for these differences and subsequent impact on health outcomes warrant further investigation.     

The bioequivalence and therapeutic efficacy of generic versus brand-name psychoactive drugs

BACKGROUND: For the purposes of drug approval, the interchangeability of a generic drug and the corresponding brand-name drug is based on the criterion of "essential similarity," which requires that the generic drug have the same amount and type of active principle, the same route of administration, and the same therapeutic effectiveness as the original drug, as demonstrated by a bioequivalence study. However, bioequivalence and therapeutic effectiveness are not necessarily the same. OBJECTIVE: This review summarizes available data comparing the bioequivalence and therapeutic efficacy of brand-name psychoactive drugs with those of the corresponding generic products. METHODS: Relevant information was identified through searches of MEDLINE, Current Contents/Clinical Medicine, and EMBASE for English-language articles and English abstracts of articles in other languages published between 1975 and the present. The search terms used were generic drug, branded drug, safety, toxicity, adverse events, clinical efficacy, bioequivalence, bioavailability, psychoactive drugs, and excipients. RESULTS: Few publications compared the bioequivalence and efficacy of brand-name and generic psychoactive drugs. Those that were identified revealed differences in the efficacy and tolerability of brand-name and generic psychoactive drugs that had not been noted in the original bioequivalence studies. Specifically, l study found that plasma levels of phenytoin were 31% lower after a switch from a brand-name to a generic product. Several controlled studies of carbamazepine showed a recurrence of convulsions after the shift to a generic formulation. After a sudden recurrence of seizures when generic valproic acid was substituted for the brand-name product, an investigation by the US Food and Drug Administration found a difference in bioavailability between the 2 formulations. Statistically significant differences in pharmacokinetic variables have been reported in favor of brand-name versus generic diazepam (P < 0.001). Finally, a case report involving paroxetine mesylate cast doubt on the tolerability and efficacy of the generic formulation. CONCLUSION: The essential-similarity requirement should be extended to include more rigorous analyses of tolerability and efficacy in actual patients as well as in healthy subjects.     

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.     

Generic psychotropic medications: issues of cost-effectiveness and patient benefit

Since the implementation of managed care, clinicians have struggled with ways to provide optimal treatment in a cost-effective manner. With the rising cost of medications, generic substitutes appear to be an answer. Some medications have proven to be less effective in generic form. Consumers may be wary of generics. However, when financially motivated, many people choose generic over brand-name products. With the hope of finding effective medications with fewer side effects, drug companies continue to spend money to find the best solutions. Research in medication efficacy is costly, which is handed over to the consumer. Benefits and efficacy of generics will be discussed.     

Converting patients from brand-name clozapine to generic clozapine

OBJECTIVE: To evaluate safety and dosage requirements when patients taking brand-name clozapine (Clozaril, Novartis Pharmaceuticals) are converted to generic clozapine (Zenith Goldline). METHODS: In November 1999, patients at Colorado Mental Health Institute at Pueblo taking Clozaril were changed to generic clozapine. Seventeen patients had been prescribed Clozaril for three years and were included in the study. Drug dosage, white blood cell (WBC) count values, and adverse drug reaction reports were compared. Data regarding patients on the brand-name product were evaluated retrospectively for the months of November, December, January, and February during the years 1996/1997, 1997/1998, and 1998/1999. These data were compared with those from the same patients after switching to generic clozapine for the same months in 1999/2000. A one-year comparison of brand-name (1998/1999) with generic drug (1999/2000) was also performed. Statistical analysis included a standard test comparing WBC values and a Brown-Forsythe test for comparing dosages. RESULTS: There were no differences between the values obtained for the brand-name and generic products. WBC counts for the three-year data resulted in a p value of 0.9992. There was no difference when comparing the samples one year prior to switching and after the switch (p = 0.9991). There was no difference in dosages at three years or one year (p = 0.9999 and p = 0.9993, respectively). No adverse events were noted with the generic product. CONCLUSIONS: No differences were found between the brand-name and generic clozapine groups with regard to WBC count, dosage, and adverse events. The conversion to the generic product is projected to save the pharmacy $90,000 annually.     

The relationship between in-hospital information and patient satisfaction after acute myocardial infarction.

BACKGROUND: Rehabilitation after acute myocardial infarction (AMI) presupposes that patients are provided with sufficient information and education to cope with the consequences of the disease. Furthermore, patient information is an important premise for patient satisfaction. AIMS: To explore and describe the relationship between received information and satisfaction with health care after AMI. In addition, we wanted to describe areas for improvement of patients' health care. METHODS: A questionnaire comprising 1) the Information Questionnaire and 2) the Patient Experience Questionnaire was sent to AMI patients, 6 weeks after discharge from hospital. One hundred and eleven patients participated. RESULTS: In general patients were highly satisfied with their health care and the more information the patient reported to receive, the more satisfied he/she was with the hospital stay. Patients were least satisfied with information about medication and possible future problems. These were the areas that patients received least information about and were also identified as the areas with greatest potential for improvement. Amount of information received was not associated to length of hospital stay. Although, younger patients reported receiving more information than older patients during the hospital stay, it was the youngest that missed information after discharge. CONCLUSION: The results indicate that it is necessary to examine the current provision of in-hospital information and education to AMI patients. Patients want more information at discharge and after returning home.     

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.     

Deleterious impact of a generic temozolomide formulation compared with brand-name product on the kinetic of platelet concentration and survival in newly diagnosed glioblastoma

Chemo-induced thrombocytopenia is a limiting toxicity among patients receiving temozolomide (TMZ) as first-line treatment for glioblastoma. We aimed to compare early platelet concentration kinetics, hematological safety profile, and impact on survival following the initiation of either the brand-name or a generic TMZ formulation. A retrospective trial was conducted in patients suffering from newly diagnosed glioblastoma. Patients were treated with TMZ at 75 mg/m² per day during six weeks, concomitantly with radiotherapy. Platelet concentration was collected each week. Primary endpoint was to perform a linear mixed-effect model of platelet concentration kinetic over weeks. A total of 147 patients were included as follows: 96 received the brand-name TMZ, and 51 received a generic TMZ formulation. Exposition to the generic was a significant variable that negatively influenced the platelet kinetics in the radiotherapy and concomitant TMZ phase, P = 0.02. Grade ≥3 chemo-induced thrombocytopenia was more frequent in the generic group: 19.6% [95% CI 8.7-30.5%] vs 3.1% [0-6.6%], P = 0.001. Exposition to the generic formulation of TMZ led to increase early treatment discontinuation due to TMZ-induced thrombocytopenia and was a worsening independent prognostic factor on overall survival: adjusted HR 1.83 [1.21-2.8], P = 0.031. These data suggest that exposition to a generic formulation of TMZ vs the brand-name product is associated with higher early platelet decrease leading to clinically relevant impacts on treatment schedule in glioblastoma. Further prospective trials are needed to confirm these results.     

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.     

General practitioners' and district nurses' views of hospital at home for palliative care

Cambridge Hospital at Home (CH@H) provides 24-h nursing in a patient's own home to patients requiring terminal and palliative respite care. To investigate views of the service, we surveyed all GPs and district nurses (DNs) in the catchment area of the scheme. Responses were received from 85% of DNs and 65% of GPs. The majority of DNs (93%) and GPs (57%) had patients referred to CH@H, whereas 90% of DNs and 42% GPs had patients admitted. The most commonly reported reason for non-referral was lack of availability of places (GPs 62%; DNs 63%). Ninety per cent DNs and 84% GPs rated continuation of the scheme as important. The most important reported benefits were 24-h care (GPs 84%; DNs 82%) and help in keeping patients at home (GPs 69%; DNs 83%). Seventy-four DNs also considered help in arranging discharge to be important. Almost half GPs and DNs considered CH@H worse than other NHS services in terms of availability and limits on the duration of care. Whilst 65% of DNs thought CH@H had reduced workload, 77% GPs reported it had made no difference or had increased it. Most indicated that CH@H made a difference in allowing patients to die at home (GPs 60%; DNs 68%). The CH@H scheme is viewed as beneficial for patients requiring palliative care at home, although GPs and DNs expressed realistic reservations about specific aspects of the scheme. With the emergence of Primary Care Trusts, NHS commissioning of hospice at home services will more firmly rest with primary care practitioners, who on balance clearly prize them.     

Communication regarding adverse drug reactions between secondary and primary care: a postal questionnaire survey of general practitioners

GPs are not always informed that their patient suffered an adverse drug reaction (ADR) while in hospital. We have conducted a postal questionnaire survey of 270 GPs in order to elicit their views regarding provision of information from secondary care regarding ADRs. Of the 141 (52.2%) GPs that replied, 127 (90.1%) saw patients that had experienced an ADR in hospital. Of these GPs, 113 (89%) stated that they encountered instances where no record of the ADR existed in patients' discharge documentation. Where written information was absent, GPs are reliant on information given to them by patients. Of those responding, none were 'very confident' of this information, while 92 (78.6%) were 'uncertain' or 'very uncertain' of this information. A sample notification form was developed. GPs were generally satisfied with its content and 110 (82.7%) thought that patients should receive a copy. Almost all GPs (135 (97.8%)) felt that it would be appropriate to provide patients with ADR warning cards. Ensuring that patients and their carers are aware of drugs to which they may be allergic or intolerant through verbal and written methods should minimize the unnecessary risks of inadvertent re-exposure.     

GPs and lesbian women in the consultation: issues of awareness and knowledge

OBJECTIVE: To study awareness of having lesbian women in the consultation among general practitioners (GPs) and their knowledge of lesbian health-related issues. DESIGN: A mailed questionnaire study using closed and open-ended questions, with an analysis using both quantitative and qualitative methods. SETTING: The city of G?teborg, Sweden. SUBJECTS: GPs working in the city of G?teborg. MAIN OUTCOME MEASURES: Frequencies are presented for closed questions. Open-ended questions are categorised and illustrated by citations. RESULTS: The response rate was 52%, but only 37% were aware of having had any lesbian patients despite many years in practice. Five per cent had ever asked their patients about sexual identity, and most questions concerning social network were put in terms of the heterosexual, nuclear family. Eleven per cent knew of any health issues relevant to lesbian women, but half of all informants declared an interest in learning more. CONCLUSION: Unreflected assumptions of heterosexuality and use of heterosexist concepts may work together in keeping the lesbian patient invisible to health care. Medical education needs to include issues of gender and sexual identity/orientation in the curriculum, and to address the health effects of marginalisation.