Table 2.

Overview of studies included in the review.

Authors	Overview of Study	Objective	Outcomes	Concerns and Gaps	Limitations	Country
1. Aladul et al. 2018 [21] Study induced between June–November 2017;	Methods: 30 min face-to-face, semi structured interviews; Sample size: n = 22; Sample: consultants, nurses, pharmacists; Profile: gastroenterology, rheumatology, diabetology;	“To investigate healthcare professionals’ perceptions and perspectives towards biosimilar infliximab, etanercept and insulin glargine and the potential barriers and facilitators to their prescribing”.	Good level of knowledge, and likely to initiate newly diagnosed patient on biosimilars, disagreement with automatic substitution of biosimilars at the pharmacy level and disagreement with multiple switching for cost reasons.	Safety and efficacy concerns (interchangeability, extrapolation), the use of different excipients, and different administration device, unavailability of all dosage strengths of the biosimilars.	Small sample size, diversity of specialties and organizational background, only four pharmacists responded to this interview.	UK
2. Giuliani et al. 2018 [22] Study induced between September 2017–October 2017	Methods: a 19-question survey; Sample size: Europe (n = 321), Asia (n = 84), US (n = 55), Africa (n = 13), Australia (n = 7); Sample: prescribers; Profile: oncology;	“To assess the current level of knowledge, understanding and comfort of use of biosimilars among prescribers”.	Most prescribers (79.2%) rate their general knowledge of biosimilars as average to high. 74.6% of prescribers were able to identify the most appropriate definition of biosimilars. 57.4% feel comfortable using an EMA-approved biosimilar. Only 62.3% understand extrapolation. 36.3% were able to identify the concept of interchangeability.	Safety concerns (interchangeability)	No hypothesis was tested, only participants of the ESMO (European Society for Medical Oncology) were included and not all responded completely.	Multicentered
3. Leonard et al. 2019 [23] Studies included between 1 January 2014–5 March 2018	Methods: systematic review; Sample size: US (n = 3) and EU (n = 17); Sample: clinicians, pharmacists, specialty physicians, nurses. Profile: rheumatology, dermatology, gastroenterology, diabetology;	“To evaluate current U.S. and European health care provider knowledge, perceptions, and prescribing behaviors of biosimilar medicines, to assess the need for clinician-directed biosimilar education”.	Overall lack of biosimilar knowledge and awareness, biosimilars mostly used in initiative treatment.	Safety and efficacy concerns, immunogenicity (interchangeability, extrapolation).	Potential for biased interpretation of results. Limitations from the included individual studies.	US, EU
4. Hernández et al. 2018 [24] Study induced between 6 September–8 September 2017	Methods: short survey comprising six questions. Sample size: n = 104. Sample: clinicians; Profile: rheumatology;	“To determine awareness of biosimilars, including prescribing practices, nomenclature, automatic substitution and ADR reporting”.	Lack of awareness considering availability of biosimilars, automatic substitution and nomenclature.	Not applicable	Not sufficient data considering methodology.	Latin America
5. Karateev et al. 2019 [25] Study conducted from 15 June–22 July 2016	Methods: survey comprising 15 questions; Sample size: n = 206; Sample: clinicians; Profile: rheumatologists, gastroenterologists, hematologists, oncologists;	“To assess levels of knowledge and attitudes towards biosimilars and key policies on their use among Russian physicians, and to define the level of interest in new information on biosimilars, and determine what evidence drives treatment decisions in Russia”.	80% of respondents lacked understanding of the differences between biosimilars and generics. 67% supported prescribing biologics by distinguishable names. 20% of respondents twice confirmed that biosimilars were different from generics and that they were not identical copies of the originator. 53% were against automatic substitution.	Safety and efficacy concerns (interchangeability).	Study findings are related to local biosimilars in Russia, and does not reflect the opinion of clinicians for international biosimilars.	Russia
6. Greene et al. 2019 [26] Study conducted from 1–19 October 2018	Methods: Survey comprising 16 strategies for overcoming barriers on 5 point scale; Sample size: n = 300; Sample: managed care and specialty pharmacists;	“To assess perceptions regarding strategies for overcoming barriers to biosimilar adoption among managed care and specialty pharmacy professionals”.	84% of respondents agreed or strongly agreed that FDA-approved biosimilars are safe and effective for patients who switch from a reference biologic. 54% agreed or strongly agreed with extrapolation.	(61%) Safety and efficacy concerns (interchangeability, extrapolation)	First 300 respondents were selected for analysis; potential for biased evaluation.	US
7. Teeple et al. 2019 [27] Study conducted between June 2016–January 2017	Methods: 15-min online survey; Sample size: n = 297; Sample: clinicians; Profile: rheumatology, dermatology and gastroenterology;	“To understand the level of familiarity of clinicians with biosimilars, their experience with non-medical switching (switching medications for reasons unrelated to patient health) of patients between biologics and their attitudes towards switching from a biologic to a biosimilar”.	88% of respondents knew the definitions of biosimilar, 84% of respondents did not agree to switch stable patients from biosimilars to originators. Only 17% of respondents would feel confident with substitution of biosimilars at pharmacy level. 50% are comfortable with extrapolation.	Concerns about interchangeability, safety and efficacy, immunogenicity, patient mental health, physician office management.	Clinicians were recruited before survey, the outcomes cannot reflect the opinion of clinicians who were not recruited.	US
8. Micó-Pérez et al. 2018 [28] Study conducted from 19 May 2016–11 September 2016	Methods: questionnaires of 34 questions; Sample size n = 701; Sample: physicians; Profile: primary care;	“To evaluate the awareness and training needs on biosimilars”.	42% of respondents knew the definition of biosimilar, 27% knew the difference between generics and biosimilars, 84% did not understand the biosimilar clinical development.	Not applicable	Not applicable	Spain
9. Aladul et al. 2019 [29] Study conducted between August 2016–January 2017	Methods: anonymized, self-administered web-based survey. Sample size n = 234; Sample: medical consultants, registrars, pharmacists, nurses; Profile: dermatology, diabetology, gastroenterology or rheumatology;	“To investigate knowledge and attitudes of different healthcare professionals in UK towards infliximab and insulin glargine biosimilars”.	76% of medical consultants/ registrars, 84% of pharmacists knew of the basic concepts of biosimilars. 6% of HCPs (mainly nurses)) had never heard of biosimilars, more comfortable with initiation of biosimilars than switching from the already in use originator.	Safety and efficacy concerns (interchangeability)	A small number of pharmacist respondents 11%,	UK
10. Cook et al. 2019 [30] Study conducted between January–May 2018	Method: a 12 question survey; Sample size: n = 77; Sample: physicians, pharmacists, advanced practice providers; Profile: oncology;	“To investigate oncology clinicians’ understanding of biosimilars and what information they need prior to adoption”.	74% of respondents didn’t know the basic definition of biosimilars; 40.3% considered biosimilars and generics as same entities. 94.8% of respondents would use an interchangeable biosimilar if it had FDA approval for interchangeability.	Knowledge gaps and the need for education regarding biosimilars is high.	Conducted at a single academic institution.	US
11. Park et al.2019 [31] Study conducted between 24 February 2017–26 March 2017	Method: a 17-question multiple-choice anonymous web survey; Sample size n = 151; Sample: clinicians; Profile: gastroenterologists;	“To assess the awareness of biosimilar monoclonal antibodies among Asian physicians”.	66.2% of respondents knew of the basic concepts of biosimilars. Only 19.2% of respondents considered that originator and biosimilars are interchangeable; only 6% felt confident in the use of biosimilar monoclonal antibodies. 86.7% were against automatic substitution at the pharmacy level.	Safety and efficacy concerns (interchangeability, extrapolation, immunogenicity)	Most respondents were only from Korea, Japan, and China.	Asia
12. Ismailov and Khasanova 2018 [32] Study conducted: Not applicable	Method: a survey of 22 questions; Sample size: n = 62 respondents; Sample: nurse, nurse practitioners‘ medical assistants, patient navigators. Profile: oncology/hematology;	“To increase oncology/hematology team members’ knowledge of biosimilars and then use an anonymous online survey to assess the knowledge gained”.	More than 90% of survey respondents identified correct answers about the definition, regulations, interchangeability, safety, cost issues, and use of biosimilars in oncology.	Knowledge gaps about safety profile, the need for education regarding biosimilars.	Did not discuss complex topics in depth (interchangeability, extrapolation, immunogenicity).	US, Colorado
13. Pawłowska et al. 2019 [33] Study conducted in September 2017	Method: a paper-based, self-administered questionnaire comprising 12 short questions; Sample size: n = 61; Sample: hospital pharmacists;	“To identify hospital pharmacist opinions towards biosimilars and investigate their usage in practice”.	68% of respondents believed that biosimilars should be used in the initiation of therapy, 75 % of respondents did not agree with the substitution of biosimilars at pharmacy level.	88% of respondents were concerned that biosimilars were not identical with originators, 48% with their immunogenicity and 44% with other pharmacokinetic properties.	The response rate was 22.5% and the results may not be representative of all hospital pharmacists in Poland.	Poland
14. Hadoussa et al. 2019 [34] Study conducted: Not applicable	Method: anonymous questionnaire comprising 15 multiple-choice questions; Sample size n = 107; Sample: clinicians; Profile: oncology and hematology;	“To evaluate the knowledge and perceptions of Tunisian oncologists and hematologists on biosimilars”.	71% of respondents were able to differentiate the biosimilar from the generic. 11% knew the difference between biosimilars and their originators. About 52.34% of respondents were in favor of justified substitution and interchangeability.	Safety and efficacy concerns, interchangeability, extrapolation.	Not applicable	Tunisia
15. Sarnola et al. 2020 [35] Studies included between 2014 until the end of 2018	Method: systematic review; Sample size n = 23 studies; Sample: Europe (n = 16); North America (n = 4); Australia (n = 1), New Zealand (n = 1) Central and South America (n = 1); Sample: clinicians; Profile: nephrology, rheumatology, dermatology, neurology, endocrinology, and oncology, gastroenterology;	“To examine physicians’ perceptions of the uptake of biosimilars”.	Physicians’ knowledge and attitudes towards biosimilars vary between studies. 49%–76% were familiar with biosimilars while 2%–25% did not know what biosimilars were. 64%-95% of physicians were against substitution of biosimilars at the pharmacy level.	Safety and efficacy concerns (interchangeability, extrapolation, immunogenicity).	The data extraction from studies was done by only one researcher.	Multicentered
16. Kabir et al. 2018 [36] Study conducted: Not applicable	Method: questionnaire-based survey; Sample size n = 250; Sample: clinicians, academics, industry experts;	“To examine whether biosimilars introduced in the Bangladesh drug industry required any further clarification with regard to industrial manufacture, distribution and clinical prescription”.	72% of industry experts, 54% of academics regard biosimilars as drugs with equivalent efficacy as their originators; 41% of clinicians saw biosimilars as bioequivalent with their originators, and no need for clinical trials to be approved. (74%) academics, (41%) clinicians, and (61%) industry experts were positive about interchangeability;	Gaps in knowledge, and harmonization between regulation and science.	Questions regarding the understanding of biosimilars were not clearly formulated by authors.	Bangladesh