02-Michieli_- 08/10/15 12:50 Pagina 109
Mini-review
Generic brands in the prevention of fragility fractures
Raffaella Michieli1 Camilla Callegaro2
1
General Practitioner, Italian College of General Practice, National Secretary, Venice, Italy 2 General Practitioner, Venice, Italy
Address for correspondence: Raffaella Michieli, MD Italian College of General Practice National Secretary, Venice, Italy E-mail: [email protected]
Summary Generic drugs are safe and effective, but their prescription in Italy is among the lowest in Europe (30% to 6070% in other Countries). According to a recently published retrospective study, generics are not statistically different from their corresponding brand counterpart in the therapy of osteoporosis, a bone defects characterized by a decrease in bone mineral density, which can lead to an increased frailty and risk of fracture. Unfortunately there are a lot of problems in compliance with these drugs: it is only about 7.19% in the first year, despite their consumption is simple and effective in the prevention of fracture. Various studies made by GPs are highlighting many barriers in the path from the contact with the doctor to the purchase at the pharmacy: the idea GPs have of generics, the patients’ perception of it, the big amount of drugs in the pharmacies and the advice that comes from the pharmacist. The published study, proving non-inferiority of generics and lack of differences in mortality and access to specialists among those using generic and brand drugs, encourages to use those drugs that not only are safe and effective, but that are also good for the economical and financial balance of Italian sanitary system. KEY WORDS: generic drug; osteoporosis; bisphosphonates.
The role of General Practitioner (GP) has been changing in the last ten years. The needs of the patients who refer to the GPs, the first free access point for all of them, mirrors our historical and social situation and the fears that people find hard to face. The need for reassurance, the awareness of the importance of prevention, the exponential growth of chronic illnesses: all these factors have increased contacts among citizens and GPs from 6.9 in 2003 to 8.1 in 2013 (1). It is a given fact that about 85% of cases hesitates facing a prescription of both a new or an old drug. Clinical Cases in Mineral and Bone Metabolism 2015; 12(2): 109-110
In the last few years, thanks to drugs research, several new drugs have been commercialized and some of them have changed the treatment chances of chronic diseases such as diabetes and osteoporosis. According to the Italian rule that regulates the prescription of some molecules, only specialists can prescribe them. The result is that not all patients take advantage of these drugs (for example, not all patients go to the specialist), and GPs have to manage both positive and negative consequences on their patients’ health, even if they cannot prescribe these drugs. Our training on drugs, during University years and daily work, is quite inadequate so that daily practice and personal experiences play a key role in prescribing them. This causes a misleading situation, but shows the need of in-depth analysis from sources that are different from industries and the “old good” Italian Agenzia Italiana del Farmaco (AIFA) site. In this general framework, about ten years ago, generic drugs came into the market. The “generic drug” is defined in the AIFA site “as equivalent or generic when it has the same qualitative or quantitative composition in active parts and the same dosage form of a referential one, and also its bioequivalence has been demonstrated with specific bioavailability test (generic and brand drugs can differ in their excipients composition). Two products are considered bio-equivalent, that is the amount of drug that moves to the circulation after any way of administration and the speed of this step after administration of a same molar amount, if their bio-availability are similar enough to produce quite the same effects in terms of efficacy and safety” (2). In Italy its reception by doctors has been half-heartedly from the start. Nowadays, not only the prescriptions are among the lowest in Europe (30 to 60-70% in other Countries) but also it is still quite common to find opposite opinions about prescribing drug. There is a lot of perplexities of their equivalence in terms of efficacy, and many colleagues describe increasing adverse effects to them attributed. These aspects become more relevant when these drugs are used for prevention, that’s to say chronically, and not to treat an acute illness. Osteoporosis is a bone defect characterized by a decrease in bone mineral density, which can lead to an increased frailty and risk of fracture (3). This is an increasing disease, with unexpected costs due to better life expectancy. Unfortunately early diagnosis is rare, and so is the appropriate therapy to avoid the most dreadful consequence: fragility fracture. In Italy they estimate osteoporosis affects about 5 million people, of which 80% are women in postmenopausal age, but we can suppose that numbers are even greater because of low consideration for the bone disease. The increase in incidence of osteoporosis, due to ageing of general population, leads to an increase in the absolute number of fractures, from 1-3% each year, with a major rate in female rather than male (4).
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R. Michieli et al. Similarly, we observe a gradual increase in vertebral fractures, with greater prevalence in female compared to male. Hip fractures are the most serious. Recent data show that 20% of fractured people die within a year after the event, 30% become permanently disabled, 40% cannot walk alone and 80% is not able to do daily activities autonomously. All these aspects make osteoporosis one of those pathology for which contact between GPs and people are more than 2% every year (1). Unfortunately data show that prevalence of therapy among women, that are more affected, is averagely 7% (HS Data 2008), and we arrive to 17.6% in those who suffered one of the complications, that is fracture (5). According to nota 79, that regulates the prescription of drugs for osteoporosis, those who are affected with fragility fractures should be in therapy to prevent re-fracture, so the above data are alarming. Furthermore there is a lot of problems in compliance with these drugs: it is only about 7.19% in the first year, despite their consumption is simple. Bisphosphonates, used for prevention of fractures, proved to be effective for this purpose, in a large randomized trial lasted for 3-5 years. In these years, the chances to use their equivalent, the so called generics, should have improved the access to therapies for a lot of people, but the influence of branded medications industries, the poor knowledge of standards required for generics and the big amount of prejudices against these drugs, caused troubles with their real replaceability. Furthermore, also consumers have prejudices if for no other reason than the idea that cheap things are less effective. According to a recently published retrospective study, generics are not statistically different from their corresponding brand counterpart (6). This study compared uniform populations with regard to gender and age, treated with brand or generic medication. It takes into account administrative databases from 2008 to 2011 referring to 347.073 patients belonging to 5 different Italian Aziende Sanitarie Locali (ASL) in Lombardia, that is 9,02% of total population in these sanitary units (totally composed of 4 million people). In relation to osteoporosis the study evaluated some differences in continuation and compliance to therapy between generic and brand alendronate, in the clinical practice.
110
The sample included 20.711 patients in 5 ASLs, with average age of 73 yrs. After 34 months, it seemed that there was not a statistically different compliance between the two groups, but data concerning continuation of therapy seemed to be in favor of generic alendronate. Unfortunately, various studies made by GPs are highlighting how many barriers there are in the path from the contact with the doctor to the purchase at the pharmacy: the idea GPs have of generics, the patients’ perception of it, the big amount of drugs in the pharmacies and the advice that comes from the pharmacist. Taking all this into consideration, it can be seen how difficult it is for the initial prescription to adhere to the final supply, unless GPs specify “non replaceable” on the prescription (but this procedure is subjected to controls). The published study, proving non-inferiority of generics and lack of differences in mortality and access to specialists among those using generic and brand drugs, encourages to use those drugs that not only are safe and effective, but that are also good for the economical and financial balance of Italian sanitary system.
References 1. 2. 3.
4.
5.
6.
VIII Report Health Search. http://www.agenziafarmaco.gov.it/sites/default/files/statement_equivalenti_o_generici_3.pdf. Quaderni della Salute - Ministero della Salute. http://www.quadernidellasalute.it/download/press-area/cartella-stampa/4-luglio-agosto-2010/4luglio-agosto-2010-Sintesi-dei-contributi.pdf. Kanis JA, on behalf of the World Health Organization Scientific Group. Assessment of osteoporosis at the primary health-care level. Technical Report. WHO Collaborating Centre, University of Sheffield, UK, 2008. Lapi F, Simonetti M, Michieli R, Pasqua A, Brandi ML, Frediani B, Cricelli C, Mazzaglia G. Assessing 5-year incidence rates and determinants of osteoporotic fractures in primary care. Bone. 2012;50:85-90. Colombo GL, Agabiti-Rosei E, Margonato A, Mencacci C, Montecucco CM, Trevisan R. Confronto tra medicinali generici e medicinali branded a brevetto scaduto: studio retrospettivo osservazionale sui dati amministrativi di 5 Aziende Sanitarie Locali in Lombardia. Plos One. 2013 Dec;8(12).
Clinical Cases in Mineral and Bone Metabolism 2015; 12(2) 109-110
Mini-review
Generic brands in the prevention of fragility fractures
Raffaella Michieli1 Camilla Callegaro2
1
General Practitioner, Italian College of General Practice, National Secretary, Venice, Italy 2 General Practitioner, Venice, Italy
Address for correspondence: Raffaella Michieli, MD Italian College of General Practice National Secretary, Venice, Italy E-mail: [email protected]
Summary Generic drugs are safe and effective, but their prescription in Italy is among the lowest in Europe (30% to 6070% in other Countries). According to a recently published retrospective study, generics are not statistically different from their corresponding brand counterpart in the therapy of osteoporosis, a bone defects characterized by a decrease in bone mineral density, which can lead to an increased frailty and risk of fracture. Unfortunately there are a lot of problems in compliance with these drugs: it is only about 7.19% in the first year, despite their consumption is simple and effective in the prevention of fracture. Various studies made by GPs are highlighting many barriers in the path from the contact with the doctor to the purchase at the pharmacy: the idea GPs have of generics, the patients’ perception of it, the big amount of drugs in the pharmacies and the advice that comes from the pharmacist. The published study, proving non-inferiority of generics and lack of differences in mortality and access to specialists among those using generic and brand drugs, encourages to use those drugs that not only are safe and effective, but that are also good for the economical and financial balance of Italian sanitary system. KEY WORDS: generic drug; osteoporosis; bisphosphonates.
The role of General Practitioner (GP) has been changing in the last ten years. The needs of the patients who refer to the GPs, the first free access point for all of them, mirrors our historical and social situation and the fears that people find hard to face. The need for reassurance, the awareness of the importance of prevention, the exponential growth of chronic illnesses: all these factors have increased contacts among citizens and GPs from 6.9 in 2003 to 8.1 in 2013 (1). It is a given fact that about 85% of cases hesitates facing a prescription of both a new or an old drug. Clinical Cases in Mineral and Bone Metabolism 2015; 12(2): 109-110
In the last few years, thanks to drugs research, several new drugs have been commercialized and some of them have changed the treatment chances of chronic diseases such as diabetes and osteoporosis. According to the Italian rule that regulates the prescription of some molecules, only specialists can prescribe them. The result is that not all patients take advantage of these drugs (for example, not all patients go to the specialist), and GPs have to manage both positive and negative consequences on their patients’ health, even if they cannot prescribe these drugs. Our training on drugs, during University years and daily work, is quite inadequate so that daily practice and personal experiences play a key role in prescribing them. This causes a misleading situation, but shows the need of in-depth analysis from sources that are different from industries and the “old good” Italian Agenzia Italiana del Farmaco (AIFA) site. In this general framework, about ten years ago, generic drugs came into the market. The “generic drug” is defined in the AIFA site “as equivalent or generic when it has the same qualitative or quantitative composition in active parts and the same dosage form of a referential one, and also its bioequivalence has been demonstrated with specific bioavailability test (generic and brand drugs can differ in their excipients composition). Two products are considered bio-equivalent, that is the amount of drug that moves to the circulation after any way of administration and the speed of this step after administration of a same molar amount, if their bio-availability are similar enough to produce quite the same effects in terms of efficacy and safety” (2). In Italy its reception by doctors has been half-heartedly from the start. Nowadays, not only the prescriptions are among the lowest in Europe (30 to 60-70% in other Countries) but also it is still quite common to find opposite opinions about prescribing drug. There is a lot of perplexities of their equivalence in terms of efficacy, and many colleagues describe increasing adverse effects to them attributed. These aspects become more relevant when these drugs are used for prevention, that’s to say chronically, and not to treat an acute illness. Osteoporosis is a bone defect characterized by a decrease in bone mineral density, which can lead to an increased frailty and risk of fracture (3). This is an increasing disease, with unexpected costs due to better life expectancy. Unfortunately early diagnosis is rare, and so is the appropriate therapy to avoid the most dreadful consequence: fragility fracture. In Italy they estimate osteoporosis affects about 5 million people, of which 80% are women in postmenopausal age, but we can suppose that numbers are even greater because of low consideration for the bone disease. The increase in incidence of osteoporosis, due to ageing of general population, leads to an increase in the absolute number of fractures, from 1-3% each year, with a major rate in female rather than male (4).
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R. Michieli et al. Similarly, we observe a gradual increase in vertebral fractures, with greater prevalence in female compared to male. Hip fractures are the most serious. Recent data show that 20% of fractured people die within a year after the event, 30% become permanently disabled, 40% cannot walk alone and 80% is not able to do daily activities autonomously. All these aspects make osteoporosis one of those pathology for which contact between GPs and people are more than 2% every year (1). Unfortunately data show that prevalence of therapy among women, that are more affected, is averagely 7% (HS Data 2008), and we arrive to 17.6% in those who suffered one of the complications, that is fracture (5). According to nota 79, that regulates the prescription of drugs for osteoporosis, those who are affected with fragility fractures should be in therapy to prevent re-fracture, so the above data are alarming. Furthermore there is a lot of problems in compliance with these drugs: it is only about 7.19% in the first year, despite their consumption is simple. Bisphosphonates, used for prevention of fractures, proved to be effective for this purpose, in a large randomized trial lasted for 3-5 years. In these years, the chances to use their equivalent, the so called generics, should have improved the access to therapies for a lot of people, but the influence of branded medications industries, the poor knowledge of standards required for generics and the big amount of prejudices against these drugs, caused troubles with their real replaceability. Furthermore, also consumers have prejudices if for no other reason than the idea that cheap things are less effective. According to a recently published retrospective study, generics are not statistically different from their corresponding brand counterpart (6). This study compared uniform populations with regard to gender and age, treated with brand or generic medication. It takes into account administrative databases from 2008 to 2011 referring to 347.073 patients belonging to 5 different Italian Aziende Sanitarie Locali (ASL) in Lombardia, that is 9,02% of total population in these sanitary units (totally composed of 4 million people). In relation to osteoporosis the study evaluated some differences in continuation and compliance to therapy between generic and brand alendronate, in the clinical practice.
110
The sample included 20.711 patients in 5 ASLs, with average age of 73 yrs. After 34 months, it seemed that there was not a statistically different compliance between the two groups, but data concerning continuation of therapy seemed to be in favor of generic alendronate. Unfortunately, various studies made by GPs are highlighting how many barriers there are in the path from the contact with the doctor to the purchase at the pharmacy: the idea GPs have of generics, the patients’ perception of it, the big amount of drugs in the pharmacies and the advice that comes from the pharmacist. Taking all this into consideration, it can be seen how difficult it is for the initial prescription to adhere to the final supply, unless GPs specify “non replaceable” on the prescription (but this procedure is subjected to controls). The published study, proving non-inferiority of generics and lack of differences in mortality and access to specialists among those using generic and brand drugs, encourages to use those drugs that not only are safe and effective, but that are also good for the economical and financial balance of Italian sanitary system.
References 1. 2. 3.
4.
5.
6.
VIII Report Health Search. http://www.agenziafarmaco.gov.it/sites/default/files/statement_equivalenti_o_generici_3.pdf. Quaderni della Salute - Ministero della Salute. http://www.quadernidellasalute.it/download/press-area/cartella-stampa/4-luglio-agosto-2010/4luglio-agosto-2010-Sintesi-dei-contributi.pdf. Kanis JA, on behalf of the World Health Organization Scientific Group. Assessment of osteoporosis at the primary health-care level. Technical Report. WHO Collaborating Centre, University of Sheffield, UK, 2008. Lapi F, Simonetti M, Michieli R, Pasqua A, Brandi ML, Frediani B, Cricelli C, Mazzaglia G. Assessing 5-year incidence rates and determinants of osteoporotic fractures in primary care. Bone. 2012;50:85-90. Colombo GL, Agabiti-Rosei E, Margonato A, Mencacci C, Montecucco CM, Trevisan R. Confronto tra medicinali generici e medicinali branded a brevetto scaduto: studio retrospettivo osservazionale sui dati amministrativi di 5 Aziende Sanitarie Locali in Lombardia. Plos One. 2013 Dec;8(12).
Clinical Cases in Mineral and Bone Metabolism 2015; 12(2) 109-110
