Substitution Of Generic Drugs Research Articles

A comprehensive review addressing the factors influencing generic drug substitution

Generic drug substitution is a common practice in healthcare systems worldwide to promote cost-saving treatments while maintaining therapeutic effectiveness. Several factors influence this substitution, including regulatory policies, safety and efficacy considerations, patient and physician preferences, and market dynamics. This review comprehensively analyzes how these factors interact and influence generic drug substitution in healthcare settings and across various therapeutic classes and highlight the importance of balancing cost-saving measures with maintaining patient safety and therapeutic efficacy. Policies and guidelines established by health authorities in each country influence the approval, interchangeability, and substitution of generic drugs. Bioequivalence and therapeutic equivalence are critical factors, particularly in drugs with narrow therapeutic indexes. Moreover, physicians’ acceptance and willingness to prescribe generic drugs, as well as patient acceptance and compliance with generic drug use, play a vital role in promoting generic substitution.

Clinical Outcome and Medical Cost of Originator and Generic Antihypertensive Drugs: A Population-Based Study in Yinzhou, China.

Background: The substitution of generic drugs can effectively alleviate the rapid growth of drug costs; however, the clinical effectiveness and medical costs of originator products and generics were barely studied in China. Objectives: To compare the effectiveness of antihypertensive drugs and hypertension-related medical costs between originator and generic initiators in Yinzhou, China. Methods: We conducted a population-based retrospective cohort study using the Chinese Electronic Health Records Research in Yinzhou (CHERRY), from July 1, 2011, to December 31, 2018. Hypertension patients initiating with originator products were compared with patients initiating with generic counterparts. We used 1:1 propensity score matching to pair the two groups based on sociodemographic, clinical, and health service utilization variables. Cox proportional regression was adopted to compare the rate of hospitalization for hypertension-related cardiovascular disease between matched originator and generic initiators. Wilcoxon matched-pairs signed-rank test was used to compare annual hypertension-related medical costs. Results: Matched pairs (10,535) of patients were included in the comparative study of originator products and generics, corresponding to seven antihypertensive drugs including amlodipine, felodipine, nifedipine, irbesartan, losartan, valsartan, and metoprolol. The average age of patients included in the analysis was around 60 years (originator vs. generics initiators: from 59.0 vs. 59.1 years in losartan to 62.9 vs. 63.6 years in nifedipine). Higher hospitalization rates among originator initiators were observed for three calcium channel blockers (hazard ratio[95% CI]: amlodipine, 3.18[1.43, 7.11]; felodipine, 3.60[1.63, 7.98]; and nifedipine, 3.86[1.26, 11.81]; respectively). The remaining four out of seven drugs of the clinical endpoint estimates showed comparable outcomes between originator products and generics (hazard ratio[95% CI]: irbesartan, 1.19[0.50, 2.84]; losartan, 1.84[0.84, 4.07]; valsartan, 2.04[0.72, 5.78]; and metoprolol, 1.25[0.56, 2.80]; respectively). Higher median annual hypertension-related medical costs were observed in originator initiators (all p < 0.001), except for metoprolol (p = 0.646). Conclusion: We observed comparable or even better clinical outcomes and less medical cost associated with the use of antihypertensive generics compared to originator counterparts. This could help increase patient and provider confidence in the efficacy of generic medicines to manage hypertension diseases.

Potential problems and recommendations regarding substitution of generic antiepileptic drugs: a systematic review of literature.

Despite the availability of generic antiepileptic drugs (AEDs), still patients and neurologists hesitate to make a switch due to assorted reasons. The objectives of this review were to evaluate the risks associated with the generic substitution of AEDs. In this context, we also summarized the recommendations of various international societies to treat epileptic patients. We used a number of electronic databases to identify the relevant published studies which demonstrated the potential problems and recommendations regarding generic substitution of AEDs. Of 204 articles found initially, 153 were selected for additional review. Subsequently, 68 articles were finally selected. This review concluded that potential problems linked with the generic substitution of AEDs could be bioequivalence issues, failure of drug therapy, emergence of adverse events and increase in the frequency of seizures. The reasons could be the pharmacokinetics properties of AEDs and unique characteristics of some epilepsy patients. Consequently, the generic substitution of AEDs affects the successful treatment and quality of life of the patients. Various guidelines recommend the well-controlled epileptic patients to avoid switching from brand-to-generic products, generic-to-brand products or generic to some other generic products.

Impact of substitution among generic drugs on persistence and adherence: A retrospective claims data study from 2 Local Healthcare Units in the Lombardy Region of Italy

BackgroundThe use of generics, equivalent but less expensive drugs, is an important opportunity to reduce healthcare expenditure. MethodsThe purpose of this study was to investigate the effect of substitution between unbranded generics on persistence and adherence to therapy in two Italian Local Health Units (ASL) in real-world clinical practice in 5 therapeutic areas using tracing drugs. Substitution of generic drugs is any change in the name of the manufacturer of the generic drug. The therapeutic areas were: diabetes (metformin); hypertension (amlodipine); dyslipidemia (simvastatin); psychiatry (sertraline); cardiology (propafenone); osteoporosis (alendronate). The retrospective analysis was carried out on the administrative databases of two Local Healthcare Units (ASL – Azienda sanitaria locale Bergamo (BG) and Pavia (PV)) in the Lombardy Region of Italy. The correlation between persistence and adherence with the different cohorts of generic substitution frequency within each therapeutic area was then calculated. ResultsAccording to the inclusion criteria, 23,773 patients were evaluated. Patients were observed for a period of 36 months starting from the first drug delivery (index date). The median age of the overall population was above 61 years in all therapeutic areas. The generic drug substitution occurred in 61.5% of patients (BG: 57.6% and PV: 65.4% respectively); Hypertension was the therapeutic area with the highest percentage of patients with substitutions. Patients' adherence, evaluated by the Medical Possession Rate (MPR) and persistence to the treatment decreases with the increase in the frequency of generic substitutions. This observation was confirmed by a statistically significant negative correlation (p-value of <0.001) between the adherence and persistence and the number of generic substitutions in each therapeutic area and Local Healthcare Units (ASL). DiscussionAdherence is one of the pillars of the patient's health management in the control and prevention of progression of the disease. Several factors, such as ageing, comorbidities, and polypharmacy, may affect adherence and influence the outcome of treatments. These results are in line with studies supporting the possibility that the change of package appearance each time a new prescription is dispensed may create confusion and ultimately reduce patients' adherence. Clinicians and decision makers should consider the impact of frequent generic substitutions on persistence and adherence, which may influence efficacy and/or safety.

Cognitive and affective determinants of generic drug acceptance and use: cross-sectional and experimental findings

An increase in generic substitution could be a viable approach to reduce global healthcare expenditures. In many countries, however, generic drug use is rather low. This study examines cognitive predictors (knowledge and beliefs) and affective predictors (general affect and sacred values) to explain generic drug acceptance and use. Data for the study come from a random postal survey conducted in Switzerland (N = 668). A detailed knowledge scale about generic drugs was developed. In addition, an experimental choice task was constructed in which respondents chose between branded and generic drugs. Generic drug acceptance as well as drug choices were influenced by knowledge, beliefs, and affect. It was also found that generic substitution is chosen less frequently for a more severe illness. Key insights could be used for developing information material or interventions aimed at increasing the substitution of generic drugs in order to make health care more affordable.

Equivalence hypothesis testing

In statistical applications, such as a comparison of two items, it is useful to know whether one item is equivalent to another. Similarly it is often desirable to know whether one item can act as a substitute for another. Applications of the concept of equivalence include blend and flavor modifications of products, substitution of generic drugs for brand-name drugs, modifications of products in response to government regulations, or component substitutions with more healthful or lower cost components. In addition, some companies develop products that are direct substitutes for those of their competitors and make advertising claims concerning their equivalence.In a recent paper, Ennis and Ennis [Ennis, D. M., & Ennis, J. M. (2009). Hypothesis testing for equivalence based on symmetric open intervals. Communications in Statistics – Theory and Methods, 38(11), 1792–1803] used an open interval to define equivalence and provided exact and approximate methods for testing a null hypothesis of nonequivalence. In this paper, a discussion of this newly developed theory of equivalence testing is presented along with a comparison to existing methods such as the “two one-sided tests” (TOST) method. We provide numerical examples to illustrate this new theory and we demonstrate that although the TOST is a convenient approximation it is fundamentally inconsistent with the specification of the null hypothesis.

Hypothesis Testing for Equivalence Defined on Symmetric Open Intervals

There are many industrial applications for which it is desirable to know whether one product can act as a substitute for another. Examples include product modifications when ingredients change, substitution of generic drugs for brand-name drugs, and modifications of products in response to government regulations. In addition, some companies develop products that are direct substitutes for those of their competitors and make advertising claims concerning their equivalency. Using an open interval within which to define equivalence, exact and approximate methods for testing a null hypothesis of non equivalence are given. In each case, examples are provided. Comparisons are made between these novel methods and existing methods, including the “two one-sided tests” (TOST) method.

平成20年度診療報酬等の改定に伴う後発医薬品の使用状況に関する保険薬局へのアンケート調査

To promote the use of generic drugs and reduce healthcare costs, the Japanese government revised some rules related to generic drugs in April 2008, such as the medical treatment fee. Following this revision, generic drug use in pharmacies and pharmacists' attitudes on generic drugs were expected to be considerably changed. This study examines the generic drug use in pharmacies and pharmacists' attitude toward generic drugs by means of a questionnaire survey, undertaken to identify and clarify the problems in their use. An anonymous questionnaire survey was conducted in 627 pharmacies, which were randomly selected from a total of 1,244 community pharmacies in Shizuoka prefecture (period of collection: September 16 to October 31, 2008). A total of 284 (45.3%) questionnaires were collected. The results revealed that 82.8% of the pharmacies charged an additional fee for the preparation of generic drugs. The preparation ratio of generic drugs in August 2008 (41.1%) was significantly higher than that in August 2007 (32.9%). Further, 69.0% pharmacies answered in the affirmative to the following item: “The 2008 revision will facilitate the preparation and substitution of generic drugs.” On the other hand, for the item about the use of generic drugs in the future, 71.4% pharmacies answered“Under consideration” or “Not using generic drugs positively.”Many pharmacies indicated certain limitations in the use of generic drugs and expressed the necessity for improvements to be made by the government and the generic drug industry; they responded in the affirmative on the items“Increase in the number of accumulating stocks” (94.7%) and“Insecurity in the quality of generic drugs” (69.7%). The findings revealed that despite the increased use of generic drugs, many pharmacists mistrust generic drugs owing to disadvantages such as an increase in the number of storing items. In the future, it will be necessary to reduce this anxiety and raise pharmacists' incentive for keeping supplies of these drugs by improving the accumulating stocks of generic drugs through legal intervention.

Debate: Substitution of generic drugs in epilepsy: Is there cause for concern?

The role of generic drugs in both the US and global marketplace has been steadily increasing over the last few years. Although generic drugs clearly represent an important economic alternative for many patients, there are reasons for concern in certain disease states. Recently, the substitution of antiepileptic drugs in patients with epilepsy has gained increased attention. Concerns over potential therapeutic inequivalence has prompted many clinicians to question current regulatory requirements for both establishing bioequivalence, as well as product substitution. The objective of this article is to present arguments both for and against the use of generic drugs and practice of generic substitution in patients with epilepsy. Regulatory requirements, pharmacokinetic methodology, and biopharmaceutical considerations are discussed.

Introduction–Decision points in epilepsy: Bedside to bench

Introduction–Decision points in epilepsy: Bedside to bench

Potential Savings from Substituting Generic Drugs for Brand-Name Drugs: Medical Expenditure Panel Survey, 1997–2000

Generic substitution is one mechanism of curtailing prescription drug expenditures. Limited information is available about the potential savings associated with generic substitution. To estimate the potential savings associated with broad substitution of generic drugs. Cross-sectional, nationally representative survey of noninstitutionalized adults. United States. Adults included in the Medical Expenditure Panel Survey Household Component, 1997-2000. Use of a multisource drug (that is, a drug available in a brand-name and > or =1 generic formulation) or a generic drug and the potential cost savings associated with broad generic substitution for all multisource products. Fifty-six percent of all outpatient drugs were multisource products, accounting for 41% of total outpatient drug expenditures. Of these multisource drugs, 61% were dispensed as a generic. If a generic had been substituted for all corresponding brand-name outpatient drugs in 2000, the median annual savings in drug expenditures per person would have been 45.89 dollars (interquartile range, 10.35 dollars to 158.06) for adults younger than 65 years of age and 78.05 dollars (interquartile range, 19.94 dollars to 241.72 dollars) for adults at least 65 years of age. In these age groups, the national savings would have been 5.9 billion dollars (95% CI, 5.5 billion dollars to 6.2 billion dollars) and 2.9 billion dollars (CI, 2.6 billion dollars to 3.1 billion dollars), respectively, representing approximately 11% of drug expenditures. Specific information about an individual's formulary was not available, so the authors could not estimate how much of the potential savings would benefit an individual or his or her health plan. Although broad substitution of generic drugs would affect only a modest percentage of drug expenditures, it could result in substantial absolute savings.

Potential Savings with Substitution of Generic Drugs for Brand-Name Drugs

Potential Savings with Substitution of Generic Drugs for Brand-Name Drugs

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.

Generic antiarrhythmic drugs: what constitutes equivalency.

The substitution of generic drugs (with or without physician awareness) is a rapidly growing phenomenon, and one that is for the most part vigorously supported by health insurors (including many government agencies), and at least tacitly supported by hospital and pharmacy managements, and some patient advocacy groups [1,2]. The motives for this enthusiasm vary. A third-party payor may be trying to save money. Hospitals and pharmacies may hope to reap a larger profit by being reimbursed about the same for a drug formulation which they acquire at lesser cost than a “brand” drug. The patient may simply be trying to strike a better deal for himself or herself by keeping their health premiums from rising, or their “out of pocket” expenses from skyrocketing. In many cases, replacement of a standard drug formulation by an apparently generic “pharmaceutical equivalent” or “pharmaceutical alternative” is safe and justifiable; however, this may not always be the case. There are concerns that periodic unexpected treatment failures or adverse reactions in patients who seemed to have been stable, may have been due to drug substitution. In cardiac electrophysiology, the greatest concern relates to the safety and efficacy of antiarrhythmic and anticoagulation treatment. Given the increasing importance drug substitution plays in clinical practice, the current standards used to determine whether a generic drug is deemed to be “bioequivalent” by regulatory authorities should be known to and agreed upon by physicians. Further, the appropriateness of such standards should be the subject of periodic critical review.

Epilepsy foundation of America statement of substitution of generic anticonvulsant drugs

Epilepsy foundation of America statement of substitution of generic anticonvulsant drugs

Access to generic drugs in the 1950s: the politics of a social problem.

From the published literature of the 1950s, the social history of anti-substitution law is analyzed in terms of sociological theory on the construction of social problems. The analysis reveals how the substitution of generic drugs for prescribed brands came to be recognized as a social problem in need of remedial legislation. The most influential party in the process was the brand-drug industry which centered the debate on matters of public health and professionalism instead of industrial profitability. The industry was able to form a coalition of interests and establish the saliency and legitimacy of the problem, even though there was no objective evidence to establish brand substitution as a hazard to health. The case fits well into the theory of social problem construction. Other issues in health care, particularly drug issues can be studied from this same perspective.