Background: Patients may experience clinical discomfort as a result of drug switches between drug products with the same active substance. Although a large market share of generic drugs is financially favourable, reduction of the number of drug switches should be strived for. However, specific causes for the drug switches are currently undocumented.
Submitted: 17 December 2020; Revised: 9 February 2021; Accepted: 11 February 2021; Published online first: 24 February 2021
Drug switches between drug products with the same active substance occur frequently and mostly between two generic drug products . Drug switching should not be clinically problematic, as interchangeability is supported by the demonstration of bioequivalence . However, a number of patients, physicians and pharmacists seem to have a negative perception of generic drugs and drug switching , and indeed for some drug adverse reactions related to drug switches have been reported . This clinical discomfort should be avoided.
Nonetheless, generic drugs are cheaper and important to reduce the costs of pharmaceutical care. In search of an optimum balance between clinical discomfort to the patients and financial benefits to the healthcare system, patients would benefit from a system in which generic drugs have a large market share, but the number of drug switches is small. A first step towards reduction of the number of drug switches is to elucidate how they arise.
The reasons for the occurrence of drug switches are currently undocumented. Logically, drug shortages will result in drug switches, but other reasons can be sought in any action by health insurers, prescribers, wholesalers and/or patients which can influence the choice of the dispensed drug product. These can differ between countries as a result of national legislation and healthcare system. However, in many countries similar policies and financial incentives are in place to promote the use of generic drugs. For instance, a number of countries have tender systems in place which favour the cheaper drug product for reimbursement from a group of interchangeable drug products . This study is performed in The Netherlands. There, generic drugs have a large market share and there is a price-based tender system to promote generic drug use , as well as mandatory prescribing by International Nonproprietary Name (INN). The number of drug shortages has increased in The Netherlands in the last decade  as a result of several issues with regard to production, distribution and quality, but also since The Netherlands is a less favourable sales market due to low prices and a small population size.
In this study, we prospectively gathered data at the pharmacy counter, both qualitatively and quantitatively, regarding the underlying reasons for drug switching in The Netherlands.
Observational field research was conducted in Dutch pharmacies during November and December 2019. A total of 400 pharmacies were approached from the database of the Utrecht Pharmacy Practice network for Education and Research (UPPER) . Pharmacies were preselected by geographical spreading, limited travel time, and the research protocol was approved by the UPPER Institutional Review Board. In a pilot study drug switches were registered during a 6-hour visit to a local pharmacy.
Drug switches were recorded by one researcher (MH) at each pharmacy’s counter, for one full day. A drug switch was defined as the replacement of a patient’s drug product with a drug product containing the same active pharmaceutical ingredient, the same strength, the same dosage form and the same route of administration, but from a different manufacturer (brand or generic). Drug switches for drugs destined for home delivery or storage in the pharmacy’s service lockers were included in the study, whereas pre-packed and pre-sorted packets for polypharmacy patients were excluded from the study for practicality. The researcher used notification systems but was also depended on pharmacy personnel to notice drug switches.
Pharmacy characteristics (predominant healthcare insurer, ownership status) were registered. Per drug switch, the reason, the INN, the dose, the manufacturer, and patient’s health insurance company were registered. Pharmacists were interviewed regarding their view on drug switching and the reasons behind drug switching. Descriptive data analysis was used.
Nationwide shortages were identified from Farmanco – the drug shortage report system from the Dutch Pharmacists Association – which contains manufacturers’ confirmed shortages lasting longer than 14 days . If a drug switch was because of a drug shortage that was neither a result of local pharmacy practice, nor nationwide, then the reason for the switch was considered a distribution issue at the wholesale level.
Out of 400 approached pharmacies, 19 were willing to participate (4.8%); for 16 pharmacies visits could be scheduled and were included in the study. These pharmacies differed by predominant health insurance company: Zilveren Kruis/Achmea (6), Menzis (4), Zorg en Zekerheid (3), VGZ/CZ (2) and Salland (1), and ownership: pharmacy chain (4), franchise (5), independent (7).
In total, 207 drug switches were registered; 13 on average per day per pharmacy (range: 4–24). As expected, most drug switches were between generic products (86%, 177/207). Moreover, 6% (12/207) of switches was from a brand-name product to a generic product. Drug switches between two brand-name products, e.g. imported from another European country, accounted for 4% (8/207), and switching from a generic product to a brand-name product accounted for 3% (7/207) of the drug switches. Finally, 1% (3/207) of the drug witches was between compounded products, see Table 1.
As depicted in Figure 1, most drug switches were a result of nationwide shortages (32%, 66/207) or the Dutch tender system (23%, 47/207). Agreements between wholesalers and pharmacists to dispense a drug product from a specific manufacturer were responsible for 12% (25/207) of the registered drug switches. In addition, 11% (22/207) of the drug switches were presumably caused by wholesalers’ distribution issues, resulting in shortage at the pharmacy, while favourable financial margins were the reason for 10% (21/207) of the drug switches. Moreover, local out-of-stock issues at the pharmacy, not caused by wholesalers’ distribution issues, were indicated as the reason for 5% (10/207) of the drug switches. Finally, 4% (8/207) were at the request of the patient, while 3% (7/207) were initiated by the pharmacists, and only one by the prescriber.
During the interview, 12 of the 16 pharmacists indicated that the number of registered drug switches was an underestimation of a normal days’ practice, whereas 4 pharmacists indicated it was representative. Fifteen pharmacists reported an annual increase in the number of drug switches. Furthermore, based on daily experience, 11 and 5 of the 16 pharmacists estimated that drug shortages and the Dutch tender system, respectively, were the main causes for drug switches. In addition, 9 pharmacists were of the opinion that generic drugs are interchangeable, while 4 believed that these are not interchangeable, and three pharmacists had a neutral position on interchangeability.
Table 1 pending to upload
Figure 1 pending to upload
To our knowledge, this study is the first to investigate reasons for occurrence of drug switches in The Netherlands. In our sample, we found that the two main reasons for drug switching are nationwide drug shortages and the price-based tender system, which combined are responsible for approximately 55% of the drug switches in The Netherlands.
It could be argued that ‘distribution issues at wholesalers’ and ‘out-of-stock issues at the pharmacy’ should also be characterized as shortages, which would increase the share of ‘shortages’ from 23% to 47% (98/207) of the total number of drug switches.
Economic drivers contribute significantly to the number of drug switches, which were most clearly identified in 22% of the total number of drug switches, i.e. deals between pharmacist and wholesalers (12%) and financially favourable margins related to reimbursement (10%).
The first study limitation is the small sample size, which could impact generalizability of the results. In addition, pharmacy visits were only in November and December while the influence of the Dutch tender system on drug switching is likely bigger in January to March . Study repetition should include more pharmacies and visits spread throughout the year. However, because we aimed to study the entire range of reasons for drug switching, the research period was still deemed adequate and perhaps more sensitive to identify issues other than the Dutch tender system.
Second, the study is limited by the semi-systematic approach, as the researcher was partly dependent on pharmacy personnel to notice drug switches. Three pharmacies did not use an automatic notification system for drug switches, which increased this dependency. Furthermore, we excluded drug switches for polypharmacy patients in pre-packed and pre-sorted packets. It must also be noted that we only succeeded in scheduling visits on ‘not too busy’ days. These limitations may have resulted in an underestimation of the total number of drug switches. Indeed, during the interview, 75% of the pharmacists (12/16) indicated that the registered number of drug switches was likely an underestimation. However, it is not expected that different reasons for drug switches would have been identified.
Overall, we present an exploration of the complex Dutch landscape of reasons for drug switching, which is, in some cases, related to policies or market structure specific to The Netherlands. Nonetheless, these findings are of international relevance. The search for an optimized drug market system, in which generic drugs simultaneously have a large market share but a low number of drug switches, is not restricted to The Netherlands. Moreover, policies and financial incentives, such as mandatory INN prescribing, or price-driven tender systems for drug reimbursement are effective in many countries. They would therefore likely result in a similar number of drug switches and similar reasons for those switches. Policymakers worldwide could thus utilize the results of our study. The results should open up the discussion about the acceptability of economic or distribution issues that cause drug switches, which in some cases result in clinical discomfort for patients. This is, however, a difficult discussion, as the issues are likely not easily solved and are perhaps essential for the financial viability of the pharmaceutical market.
No external funding was received for this research project.
This manuscript is not intended to reflect the opinion of the Medicines Evaluation Board in The Netherlands nor any of the working parties or scientific committees of the European Medicines Agency.
The protocol for this research was approved by the UPPER Institutional Review Board of the division of Pharmacoepidemiology and Clinical Pharmacology of Utrecht University, The Netherlands. For each participating pharmacy, a written informed consent was provided by the head pharmacist.
What is already known about this subject:
– Switching between (generic) drugs of the same active substance results in adverse drug reactions
– Drug switching occurs frequently in Dutch pharmacies
What this study adds:
– Knowledge of the reasons for drug switches to occur in The Netherlands
– Evidence to support discussion on policy interventions aiming for a reduction in the number of drug switches
Competing interests: The authors declared no competing interests for this work.
Provenance and peer review: Not commissioned; externally peer reviewed.
1Medicines Evaluation Board, Utrecht, The Netherlands
2Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre, Maastricht, The Netherlands
3Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands
4Department of Pharmacy, Radboud University Medical Centre, Nijmegen, The Netherlands
5Department of Clinical Pharmacy and Toxicology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, The Netherlands
6Department of Pharmacology and Toxicology, Radboud University
Medical Centre, Nijmegen, The Netherlands
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Author for correspondence: Pieter J Glerum, MSc, CBG-MEB, PO Box 8275, NL-3503 RB Utrecht, The Netherlands
Disclosure of Conflict of Interest Statement is available upon request.
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