Once the period of ‘exclusivity’ on a reference medicine expires, it is possible to apply for marketing of a generic version of that medicine. By definition, a generic product is considered interchangeable with the innovator brand product when it demonstrates the same qualitative and quantitative composition in active substances, the same pharmaceutical form and bioequivalence with the reference product after a single dose. In Italy in 2014, the use of generics represented 51.1% of the National Health Service expenditure with an increase of þ6.6% with respect to 2013 and 70.4% of the total DDD with an increase of þ11.9% over 2013. The percentage of the national expenditure for bioequivalent generics (off-patent generic drugs, excluding the off-patent originator) represented 28.8% of the total expenditure for out-of-patent drugs. Even though the use of generics is important to reduce healthcare expenditure, there is a concern it may affect the attitude of patients in following the prescribed indications, which are not directly related to bioequivalence.
A specific reason for attention was raised on the effect of generic substitution (i.e., switches between brand names and generics, and switches between generics), which is believed to affect medication safety and to create insecurity in patients taking multiple drugs by the changes in the appearance of their drugs. As a consequence, patients may make mistakes or double-medicate, leading in turn to increased drug non-adherence, therapeutic failure, unnecessary complications, disability and increased adverse events even very serious ones. A survey conducted on behalf of the Swedish government in 2004 concluded that one-third of all patients feel worried when their drug is substituted and one-third find it confusing when the names change on their prescribed medication. The possibility that variation in packaging and pill appearance may affect adherence is also a reason of concern.
The use of generics, equivalent but less expensive drugs, is an important opportunity to reduce healthcare expenditure.
The purpose of this study was to investigate the effect of substitution between unbranded generics on persistence and adherence to therapy in 2 different Italian Local Health Units (ASL); within real-world clinical practice across 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 e 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.
According to the inclusion criteria, 23,773 patients were evaluated. Patients were observed for a period of 36months 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), as well as their persistence in terms of 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).
Adherence 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.