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Original research
Physicians’ perceptions of the uptake of biosimilars: a systematic review
  1. Kati Sarnola1,
  2. Merja Merikoski1,2,
  3. Johanna Jyrkkä1,
  4. Katri Hämeen-Anttila1
  1. 1Assessment of Pharmacotherapies, Finnish Medicines Agency Fimea, Helsinki, Finland
  2. 2City of Kuopio, Kuopio, Pohjois-Savo, Finland
  1. Correspondence to Dr Kati Sarnola; kati.sarnola{at}gmail.com

Abstract

Objectives To examine physicians’ perceptions of the uptake of biosimilars.

Design Systematic review.

Data sources MedLine Ovid and Scopus databases at the end of 2018.

Eligibility criteria Original scientific studies written in English that addressed physicians’ perceptions of the uptake of biosimilars.

Data extraction and synthesis The search resulted in altogether 451 studies and 331 after removing duplicates. Two researchers examined these based on the title, abstract and entire text, resulting in 20 studies. The references in these 20 studies were screened and three further studies were included. The data of these 23 studies were extracted. All the publications were quality assessed by two researchers.

Results Most of the selected studies were conducted in Europe and commonly used short surveys. Physicians’ familiarity with biosimilars varied: 49%–76% were familiar with biosimilars while 2%–25% did not know what biosimilars were, the percentages varying from study to study. Their measured knowledge was generally more limited compared with their self-assessed knowledge. Physicians’ perceptions of biosimilars also varied: 54%–94% were confident prescribing biosimilars, while 65%–67% had concerns regarding these medicines. Physicians seemed to prefer originator products to biosimilars and prescribed biosimilars mainly for biologic-naive patients. They considered cost savings and the lower price compared with the originator biologic medicine as the main advantages of biosimilars, while their doubts were often related to safety, efficacy and immunogenicity. 64%–95% of physicians had negative perceptions of pharmacist-led substitution of biologic medicines.

Conclusions Physicians’ knowledge of and attitudes towards biosimilars vary. Although physicians had positive attitudes towards biosimilars, prescribing was limited, especially for patients already being treated with biologic medicines. Perceptions of pharmacist-led substitution of biologic medicines were often negative. Education and national recommendations for switching and substitution of biologic medicines are needed to support the uptake of biosimilars.

  • biosimilar
  • biologic medicine
  • physician
  • perception
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Strengths and limitations of this study

  • This is the first systematic review conducted solely on physicians’ perceptions regarding the uptake of biosimilars.

  • The literature search was conducted with the help of an experienced information specialist.

  • Publications selected for this review were quality evaluated by two researchers independently.

  • The quality evaluation protocol was compiled from four existing evaluation protocols.

  • The data in the studies included in this review were mainly collected before 2017.

Introduction

Biologic medicines consist of one or multiple biologic active substances and are often manufactured through biotechnology.1 2 They were first developed mainly for rare diseases, but have also improved the treatment of many common diseases such as diabetes, arthritis and psoriasis.1 The flipside of this transformation are the high costs of biologic medicines, which have contributed to increased medical costs globally.3

Biosimilars are biologic medicines highly similar to the originator biologic medicines and with the same standards of quality, safety and efficacy.2–4 Biosimilars are not clinically meaningfully different from the existing reference product. They are not regarded as generic medicines due to the complex manufacturing process and the natural variability between manufacturing batches of biologic medicines. The comparability of the product with the reference product has to be demonstrated, but clinical trials are not required. As a result, biosimilars can be brought to the market at a lower cost in comparison with the originator biologic product. The uptake of biosimilars could lead to healthcare cost savings and better patient access to costly biologic therapies.5 By the end of 2018, 50 biosimilars had received marketing authorisation in Europe and 15 in the USA.6 7

Despite their demonstrated comparability and cost-saving potential, biosimilars have not fully penetrated the market of biologic medicines. The European Union accounts for 80% of the global biosimilar market, but biosimilars constitute only 1% of the total sales of biologic medicines.8 9 It has been stated that decisions to select biologic medicines may be either policy driven or made by individual physicians, which has raised the need to assess the prescribing of biosimilars in a critical manner.10 11 Physicians’ reluctance to prescribe biosimilars may restrict potential savings in medical costs that could enable biologic treatment of larger patient populations and provide more cost-effective treatment, as similar benefits could be gained by using less expensive treatments. Therefore, it is vital to study physicians’ attitudes towards and perceptions of the uptake of biosimilars. The published information on the topic is somewhat contradictory. A previous systematic review focused on healthcare providers’ knowledge, perceptions and prescribing behaviours of biosimilar medicines.12 As the role of physicians is critical in the uptake of biosimilars and gaining the cost-saving potential, a wider understanding of physicians’ perceptions of the uptake of biosimilars with a critical quality evaluation of the published literature was needed. Thus, the aim of this systematic review was to examine physicians’ perceptions of the uptake of biosimilars.

Materials and methods

Literature search

A systematic literature search was conducted in the MedLine Ovid and Scopus databases at the end of 2018. These databases provide a comprehensive selection of scientific publications from the disciplines of pharmacy and medicine. The systematic search strategy (online supplementary appendix 1) was constructed by the research group, and the search was conducted by an experienced information specialist.

The initial search resulted in 451 studies. After removal of duplicates (n=120), 331 studies remained. These studies were examined based on the title, abstract and entire text by two researchers independently (KS and MM). Of the 331 studies, 152 were excluded based on the title, 148 based on the abstract and 11 based on the entire text. At each stage, the researchers shared their views of the studies, discussed possible differences of opinion and reached a consensus opinion based on the discussion. The inclusion and exclusion criteria of this systematic review are presented in table 1. A total of 20 publications were selected for further analysis. Furthermore, the reference lists of these 20 articles were screened and three further articles that met the inclusion criteria were selected and included in this review, bringing the final number of included studies to 23. The PRISMA flow chart explaining the study inclusion process is presented in figure 1.

Table 1

Inclusion and exclusion criteria of studies of this systematic review

Figure 1

PRISMA flow chart explaining the study inclusion process.

Quality assessment

Each of the 23 selected studies was concisely reviewed. Quality assessment was conducted according to a protocol adapted from the protocols of Åkesson et al, Tong et al, the Joanna Briggs Institute and the Swedish Agency for Health Technology Assessment and Assessment of Social Services13–16 (online supplementary appendix 2). The adapted protocol was developed and used in the quality evaluation because the study designs of the included studies varied and there was no single protocol that was suitable for evaluating the studies in a concise manner. Two researchers conducted quality assessments individually and then compared their reviews. Differences in opinions (n=6) were discussed and final evaluation was reached by consensus. In the Results section of this systematic review, the studies assessed as having high quality are emphasised more than those with moderate or low assessed quality.

Data extraction and analysis

A meta-analysis was not conducted due to the various methods and inclusion of both qualitative and quantitative approaches in the studies included in this review. The following information was extracted from the included studies: general information (authors, year of publication and country of publication), aims, methods and results. In regard to results, seven topics for data extraction were identified based on the topics discussed in the publications and discussions within the research group. These topics concerned the physicians’ (1) self-rated knowledge of biosimilars, (2) measured knowledge of biosimilars, (3) information sources about biologic medicines, (4) attitudes towards and experienced advantages and disadvantages of biosimilars, (5) actions in the initiation of biosimilars for biologic-naive patients, (6) actions in switching between originators and biosimilars for patients already being treated with biologic medicines, and (7) thoughts on pharmacist-led substitution of biologic medicines. In the Results section of this systematic review, these seven topics are presented within four broader themes: physicians’ (1) self-rated and measured knowledge of biosimilars and information sources on biologic medicines, (2) attitudes towards and experienced advantages and disadvantages of biosimilars, (3) perceptions of the treatment initiations with biosimilars and on the switches between originator biologic medicines and biosimilars, and (4) attitudes towards pharmacist-led substitution of biologic medicines. All percentages presented in this article refer to the percentages shown in the included studies of physicians with a certain opinion. If more than one study investigated the topic, the ranges of percentages in these studies are shown.

Results

Study characteristics

Physicians’ perceptions of biosimilars have been studied mainly in Europe (n=16)10 17–30 and North America (n = 4).31–34 Single studies have been conducted in Australia (n=1),35 New Zealand (n=1),36 Central and South America (n=1)37 and with participants from multiple African, European and Middle Eastern countries (n=1)38 (table 2). All the studies were published between 2014 and 2019, most of them (n=20)10 17 20–22 24–38 in 2017 or earlier. The data presented in the studies were collected between 2013 and 2017. Most of the 23 selected publications used surveys, typically web-based questionnaires with 11–22 questions, or fully structured short interviews (n=17).10 17 18 22–27 30–32 34–38 In addition, there were one qualitative interview study19 and two real-world cross-sectional studies (n=2)28 29 in which physicians filled a survey form and reported their prescribing, then recruited patients who also filled a questionnaire form to provide information on how the reported prescribing was actualised in practice. There were also discrete choice method surveys (n=2)20 21 in which prescribers were given a hypothetical scenario and possible treatment options, and had to choose their preferred alternative.39 Furthermore, there was one literature review with a survey of the market uptake of biosimilars.33

Table 2

Characteristics of the 23 studies included in this systematic review

Quality assessment

Of the 23 included studies, seven10 18 20 21 23 27 34 were evaluated as high, six19 22 28–31 as moderate and nine17 24–26 32 33 35 37 38 as low in quality based on the criteria used in this review (table 3). Publications evaluated as high in quality often included well-described and logically presented methods and results sections together with a critical discussion section, which those evaluated as moderate or low quality typically lacked. In general, the quality assessment revealed that there is a lack of valid instruments and studies using qualitative research methods.

Table 3

Summary of the quality evaluation of the 23 included studies of this systematic review

Self-rated and measured knowledge on biosimilars and sources of information (n = 18)

There was wide variation in physicians’ self-rated knowledge of biosimilars (table 2). Most physicians reported having at least a basic understanding of the topic: 5%–44% reported that they were very familiar and 49%–76% that they were familiar with biosimilars.10 24 26 27 31 34–36 However, 2%–25% of the physicians reported that they did not know what biosimilars are. Physicians with more years of practice and those with specialisation consider themselves more familiar with biosimilars in comparison with less experienced colleagues and general practitioners.10 22 34

Although according to their self-rating the physicians generally were familiar with biosimilars, their actual measured knowledge of the topic appeared to be weaker (table 2). From 18% to 66% of the physicians incorrectly described biosimilars as generic medicines, whereas 31%–72% thought they are structurally identical to originator medicines.10 22 23 25 32 34 35 37 38 However, in three studies, 76%–100% were able to state the complete definition of a biosimilar correctly.18 19 27

The physicians used several sources of information about biologic medicines, such as scientific publications (25%–84%), self-study (35%–84%), pharmaceutical companies (32%–76%), guidelines from professional societies (26%–75%), educational events and conferences (17%–71%), other published literature (46%–68%), physician colleagues (28%–54%), safety registries (52%) and pharmacist colleagues (19%)10 17 19 22 24–26 30–32 35 37 (table 2). One study found that information sources may vary according to the physicians’ educational background, as the most common information source for medical specialists were the guidelines from professional societies, whereas for general practitioners they were national or hospital formularies.10

Attitudes towards and experienced advantages and disadvantages of biosimilars (n=21)

The physicians’ reported attitudes towards biosimilars seem contradictory10 20–25 27–29 31–34 36–38 (table 2). Some (6%–38%) physicians consider biosimilars and originator products interchangeable, while others (28%) never think so.25 27 Some studies show that 65%–67% of physicians have concerns regarding biosimilars,20 21 while others report that 54%–94% of physicians feel somewhat or very confident prescribing biosimilars.10 22 24 34 36 Regardless, a positive attitude towards biosimilars does not automatically translate into prescribing, as physicians seem to prefer originator products to biosimilars.20 27 34 Some studies indicate that there might be differences in attitudes towards biosimilars between specialties: gastroenterologists seem to be frequent prescribers of biosimilars, while dermatologists and rheumatologists seem less enthusiastic.19 23 32

The main experienced advantages of biosimilars are cost savings,18 22–25 31 lower price in comparison with the originator biologic medicine31 38 and the possibility to get experience with the new product28 29(table 2). In addition, single studies reported that robust pharmacovigilance studies,18 easier access to treatment for patients,31 and approval of the European Medicines Agency or the Food and Drug Administration38 were motivators for prescribing biosimilars. The most commonly reported disadvantages were distrust in safety,10 18 22 31 33 efficacy,10 18 22 31 33 immunogenicity10 25 31 and indication extrapolation of biosimilars10 34 or the lack of clinical data on biosimilars.24 26 Single studies also suggested that the quality,10 traceability10 or tolerability22 of biosimilars and patients’ concerns towards biosimilars22 were disadvantages.

Initiation of biosimilars and switches between original biologic medicines and biosimilars (n=21)

The physicians (39%–89%) seemed more willing to prescribe a biosimilar for biologic-naive patients rather than for patients already being treated with biologic medicines10 20 23 25 27–29 31 33–38 (table 2). In discrete choice experiment studies, for example, 61%–84% of gastroenterologists chose biosimilars in at least one of the choice sets for biologic-naive patients.20 21 However, there are also other factors affecting the medicine selection, such as the cost of the medicines. One article reported that if cost were not an issue, only 11% of physicians would choose a biosimilar for treatment initiation.34 In addition, some studies suggest that some personal characteristics may influence the uptake of biosimilars by individual physicians: men, senior consultants and those treating more patients,21 along with those more familiar with brand name medicines and uncertain of the long-term safety of biosimilars34 were often unlikely to choose a biosimilar as initial therapy. Within medical specialties, gastroenterologists (95% with no concerns) appear to be the most confident to use biosimilars in treatment initiations, followed by rheumatologists (92%), dermatologists (79%) and diabetologists (75%).23

The physicians did not seem willing to switch from an originator biologic medicine to a biosimilar10 20–25 32–34 36 37 (table 2). The proportion of physicians willing to switch from an originator to a biosimilar was 51% or less, except in a single study in which the percentage was 91%.10 22 24 25 32 34 36 Similarly, when it comes to treatment initiation, the medical specialty of the physicians affected their willingness to switch biologic medicines.23 Gastroenterologists (95% with no concerns) seemed the most confident concerning switching, followed by dermatologists (78%), diabetologists (69%) and, notably, rheumatologists (53%).

Pharmacist-led substitution of biologic medicines (n=9)

Most physicians (64%–95%) were concerned about or disagreed with pharmacist-led substitution of biologic medicines10 19 22 24–26 31 34 35 (table 2). The studies suggest that having full autonomy in medicine selection and being fully aware of which medicines their patients receive was often crucial for physicians.10 26 31 35 However, according to a single study, 88% of the physicians believed that pharmacist-led substitution without consulting physicians will be allowed in the future.31

Discussion

In this systematic review, physicians’ knowledge of biosimilars varied widely. In general, their measured knowledge was weaker than their self-assessed knowledge. They used multiple sources of information about biologic medicines, most commonly scientific publications, pharmaceutical companies and professional societies. Similarly, their perceptions of biosimilars and the uptake of these medicines also varied. They seemed to prefer originator products to biosimilars, and prescribe biosimilars mainly for biologic-naïve patients. They consider cost savings and the lower price compared with the originator biologic medicines to be the main advantages of biosimilars, while their doubts were related to the safety, efficacy and immunogenicity of biosimilars. Most of the physicians had negative perceptions of pharmacist-led substitution of biologic medicines. The results in this review are in line with an earlier systematic review of healthcare providers’ perceptions of biosimilars.12

Physicians’ knowledge of biosimilars

This study found that physicians’ knowledge of biosimilars in many cases was inadequate, and this may contribute to the low prescribing and uptake of biosimilars.10 12 32 Although this issue has been widely recognised, there is limited evidence of the effectiveness of education interventions on prescribing.40 In contrast, academic detailing has proven to be effective in steering prescribing.41 42 This is a method in which a trained educator meets with a healthcare professional and shares the latest evidence-based information on the topic concerned.43 Besides its effectiveness in steering prescribing patterns, academic detailing has been proven to improve the cost-effectiveness of prescribing and reduce medical costs.44 45 It is vital that in the near future physicians and other healthcare professionals are provided targeted, evidence-based information on biosimilars to support their uptake and to gain the full cost-saving potential of these medicines.46 47 The educational activities of medical societies is also vital in the distribution of appropriate biosimilar information.11

Physicians’ attitudes towards biosimilars and means to enhance the uptake

According to this study, physicians’ attitudes towards biosimilars were contradictory, and the prescribing of biosimilars is more often directed to biologic-naive patients despite the convincing evidence that supports switching.48 Prescribing decisions can either be made by individual physicians or steered by binding policies that vary across countries. Furthermore, besides actual steering policies, there are general differences across health systems in prescribing, dispensing, pricing and reimbursement of biologic medicines that may have effects on the uptake.10 11 In Denmark and Norway, for example, hospital, regional or national tendering is in use, resulting in significant savings in the purchase of biologic medicines.11 49 50 Some countries have implemented incentives for healthcare professionals.11 Prescription quotas defining the ratio of biosimilars of all prescribed biologic medicines are in use in Germany and Sweden,51 while profit-sharing agreements making it possible to use the savings from biosimilar uptake for the benefit of the clinic or the organisation are used in Sweden and the UK.52 53 Pharmacist-led substitution of biologic medicines can also be seen as a potential means to enhance the uptake of biosimilars.11 31 This is legislatively possible in France and in the USA, and for some biological medicines also in Australia.54–56 Furthermore, the implementation of pharmacist-led substitution is currently ongoing in some European countries.46 57 All these initiatives highlight that the weak uptake of biosimilars has been acknowledged globally, and there is a need to discover sustainable means to enhance and stabilise their uptake.11 What complicates the issue is that, for example in Europe, even though the biosimilarity between biologic medicines is stated by the European Medicines Agency, decisions on the interchangeability and substitution are made at the national level. In order to support the uptake of biosimilars, educational measures for both healthcare professionals and patients are needed, although the role of national recommendations, policies and steering in the switching and substitution of biologic medicines should not be understated.31 46 47

Strengths and limitations

The main strengths of our review are that the literature search was conducted with the help of an experienced information specialist, and that the step-by-step review and inclusion of publications as well as the quality evaluation of studies was conducted independently by two researchers in order to avoid bias.58 Compared with the previous systematic review,12 this review included 12 more original publications due to a wider literature search focus. Furthermore, the current study excluded conference papers and Letters to Editors because for the purpose of the quality assessment full information about the methodology of the included studies was needed. One major limitation of this review is that the study-by-study data extraction was done by only one researcher. Furthermore, theses or reports by authorities that could have included research results were excluded from this study. In addition, none of the available protocols for quality assessment covered different types of study settings, so the protocol used in this study was compiled from four separate protocols. Moreover, the included studies were conducted in different countries with unique regulatory laws and policies that undoubtedly affect the uptake and prescribing of biosimilars at the national level. However, it is vital to compile studies from different countries with different systems and policies in order to form a comprehensive view of the current situation concerning the uptake of biosimilars. Another notable point is that the data in the studies included in this review were mainly collected in 2017 or earlier. The topic is very timely and perceptions of the uptake of biosimilars may change in light of new research information, interventions and experience in using these medicines. Thus, there is a need to continue examining physicians’ perceptions, both in general and with different disciplines, particularly with qualitative research methods. Further studies are needed to explore the differences between disciplines in the attitudes towards and prescribing of biosimilars, as the reasons behind these differences could not be explored in detail based on the studies included in this review.

Practical implications

This systematic review provides up-to-date knowledge about physicians’ perceptions of the uptake of biosimilars, and highlights the need for further education and steering on this issue. The knowledge provided by the review may be used in visioning future means to enhance the uptake of biosimilars that could include information sharing and educational interventions by means of, for example, academic detailing. The uptake of biosimilars may also be enhanced by implementing national policies or steering procedures that support the uptake, by means of pharmacist-led substitution of biologic medicines, for example.

Conclusions

This systematic review shows that physicians’ knowledge of and attitudes towards biosimilars vary. Although physicians have positive attitudes towards biosimilars, prescribing is limited, especially for patients already being treated with biologic medicines. Perceptions of the pharmacist-led substitution of biologic medicines are often negative. Education and national recommendations and policies for switching and substitution of biologic medicines are needed to support the uptake of biosimilars.

References

Footnotes

  • Contributors KS, MM, JJ and KH-A contributed to the conception or study design. KS and MM acted as principal investigators in the search and evaluation of the literature and in the quality assessment. KS drafted the manuscript. All authors participated in critical revision of the manuscript and approved the final version.

  • Funding This study is a part of a larger research project funded by the Social Insurance Institution of Finland (Kela), grant (31/26/2017).

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as online supplementary information.