Awareness, Knowledge, and Perceptions of Biosimilars Among Specialty Physicians
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- Cohen, H., Beydoun, D., Chien, D. et al. Adv Ther (2016) 33: 2160. doi:10.1007/s12325-016-0431-5
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The Biosimilars Forum conducted a survey through an independent organization from November 20, 2015 to January 4, 2016 in order to assess current levels of awareness, knowledge, and perceptions of biosimilars among US specialty physicians who already prescribe biologics. The survey was intended to provide a baseline level of knowledge about biosimilars and will be repeated in 2–3 years in order to monitor trends over time.
A 19-question survey was created by the Biosimilars Forum and was administered by an independent third party.
Responses were obtained from 1201 US physicians across specialties that are high prescribers of biologics, including dermatologists, gastroenterologists, hematologist-oncologists, medical oncologists, nephrologists, and rheumatologists.
The results of this survey highlight a significant need for evidence-based education about biosimilars for physicians across specialties. Five major knowledge gaps were identified: defining biologics, biosimilars, and biosimilarity; understanding the approval process and the use of “totality of evidence” to evaluate biosimilars; understanding that the safety and immunogenicity of a biosimilar are comparable to the originator biologic; understanding the rationale for extrapolation of indications; and defining interchangeability and the related rules regarding pharmacy-level substitution.
Funding: Biosimilars Forum.
KeywordsBiologic Biosimilar Biosimilarity Extrapolation Immunogenicity Interchangeability Originator biologic
Biosimilars are biological products that are approved on the basis of multiple comparability steps that demonstrate high similarity to an already FDA-approved originator biologic, and that have demonstrated no clinically meaningful differences in quality, safety, and efficacy. As of August 2016, three biosimilars have been approved by the FDA, of which one has already been marketed since September 2015. Approximately 60 other biosimilars are in clinical development in the US [1, 2, 3, 4].
Although biosimilars are relatively new to the United States (US) market, they have been safely utilized in Europe (since 2006), Australia, Canada, Japan, and several other countries worldwide, resulting in more than 400 million patient-days of exposure to more than 20 biosimilars for numerous molecules, including recombinant human growth hormone (rhGH), erythropoietin, filgrastim, insulin, follitropin, infliximab, and etanercept [5, 6, 7]. As more biosimilars enter the US market over the coming years, they are expected to expand patient access to life-saving medications for difficult-to-treat diseases, such as cancer, anemia, and endocrine and autoimmune disorders (e.g., multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease) because they will offer an alternative to existing biologics for Medicare, Medicaid, and the private sector .
Several of the leading biosimilar sponsors created the Biosimilars Forum in 2015 to advance biosimilars in the US with the intent of expanding access and availability of biological medicines to improve health care . The Biosimilars Forum provides evidence-based information to inform and support public policies that encourage awareness, access, and adoption of biosimilars. Current members include: Allergan, Amgen, Boehringer-Ingelheim, Coherus, EMD-Serono, Merck, Pfizer, Samsung Bioepis, Sandoz, and Teva.
When generic drugs first became available in the US in the 1980s, physicians required a clear understanding of this new class of drugs before they were comfortable prescribing them to patients . Similarly, it is expected that physicians will also require an in-depth understanding of biosimilars before they feel comfortable offering these new treatment options to their patients. In order to assess current levels of awareness, knowledge, and perceptions of biosimilars among specialty physicians who already prescribe biologics, the Biosimilars Forum conducted a survey through an independent organization from November 20, 2015 to January 4, 2016. The survey was intended to provide a baseline level of knowledge among specialty physicians. A similar survey will be conducted in 2–3 years time with the same design in order to monitor trends in the awareness, knowledge, and perceptions of biosimilars over time.
A 19-question survey was created by the Biosimilars Forum, and a third-party organization, SERMO (a global social network organization for physicians), was contracted to conduct the survey. An attempt was made to word all questions in a neutral manner. Respondents were not informed that pharmaceutical companies had created the questionnaire because it was felt that knowledge of this fact might bias the responses, although it was prospectively planned to disclose this fact at the time of publication. Responses were obtained from 1201 US physicians across specialties that are high prescribers of biologics, including dermatologists, gastroenterologists, hematologist-oncologists, medical oncologists, nephrologists, and rheumatologists. The profile of SERMO US physician members closely mirrors that of all US physicians (as measured by the American Medical Association (AMA)) . The anonymous respondents represented a cross-section of years of experience primarily between 6 and 30 years, although the largest portion of respondents was in practice for 11–20 years (32.8%). Survey respondents who did not prescribe biologics were excluded from the survey, and were not counted among the 1201 participants.
The survey examined a range of topics important to establish the foundation of biosimilars in the US, including: physician understanding of biosimilars and perceptions of critical quality attributes; safety and efficacy; biosimilarity; extrapolation; interchangeability; approval requirements and processes; existing and pending regulations regarding use; and value to patients. Ongoing policy issues that were not yet resolved by the US Food and Drug Administration (FDA) were explicitly excluded, although questions were posed about the concept of interchangeability since that concept can impact the use of biosimilar products in the US. The survey was also designed to gather information about physician intent to use biosimilars in their practice, the impact of expanded access to biologics and biosimilars on patient costs, and greater adherence with treatment regimens. The survey results are limited to the specialty groups surveyed and cannot be extrapolated to other physician groups or healthcare professionals.
There are several limitations to the survey. At the time of the survey, only one biosimilar was approved and marketed in the US as a supportive treatment for a hematology–oncology indication. This product was first available in the US in September 2015, only 3–4 months before the survey was conducted. As a result, there was no immediate need for physicians in the other specialties surveyed to be knowledgeable about biosimilars. The survey represents a snap shot in time; therefore, it may not reflect the awareness, knowledge or perceptions of biosimilars by specialty physicians today. Biosimilars have since received significant press coverage, and several healthcare practitioner societies, patient advocacy groups, companies, and trade associations (including the Biosimilars Forum) have initiated biosimilar educational activities geared toward healthcare professionals after the survey was completed.
This article does not contain any new studies with human or animal subjects performed by any of the authors.
Results and Discussion
General Awareness of Biologics and Biosimilars
Most respondents (75%) appear to trust FDA approval decisions; however, they will still want additional information when making treatment decisions (Fig. S2 in Supplementary Materials). A small group of respondents (13%), predominantly dermatologists and rheumatologists, will not solely trust the FDA’s assessments and decision to approve the biosimilar and will seek more information. Presumably, these physicians will decide which medications to use based on their own assessments. The survey did not probe further into how those decisions would be made.
Understanding and Perceptions of Key Concepts Related to Biosimilars
One fundamental premise of biosimilars is that a product will be clinically evaluated in one or more indications of use, and the FDA may ‘extrapolate’ the totality of data to approve the biosimilar for use with other indications for which the originator biologic is approved. While only 12% of respondents surveyed are comfortable with the concept of extrapolation (Fig. S3 in Supplementary Materials), separate questions that assessed details of extrapolation reveal that most physicians are not familiar with the concept. This lack of knowledge was further highlighted at a US Advisory Committee meeting held on July 12–13, 2016,  whereby the panelists became more accepting of the concept after it was explained that extrapolation was based on totality of evidence data from the originator biologic molecule to the biosimilar molecule and not from the clinical aspects of one indication to another indication.
Almost 60% of respondents correctly understood that to be approved as “interchangeable,” a biosimilar must be shown to be safe and effective for back-and-forth switching with no negative impacts to safety or efficacy (Fig. S4a in Supplementary Materials). However, there is a lack of awareness or misinformation about the term ‘interchangeable’ (Fig. S4b–e). Overall, one-third of respondents believe that the term means that approval of a biosimilar implies interchangeability with the originator biologic (Fig. S4b). In fact, an additional category was created within the US regulatory pathway for an interchangeable product. As of the time of writing of this article, the exact nature of the additional information that will be needed has not yet been defined, but is thought to include additional clinical data beyond that provided to establish biosimilarity. An overwhelming 80% of the respondents were not aware that interchangeability would enable a pharmacist to switch between originator biologic and biosimilar, and vice versa (Fig. S4c).
Perceptions of Safety and Efficacy
Finally, the majority of physicians (85%) appreciate that, as is true for all biologics, the immunogenicity profile of a biosimilar will not be completely known pre-approval (Fig. S5 in Supplementary Materials). To alleviate possible concerns about immunogenicity of a given biosimilar, it will be important to communicate the safety data that will be obtained from post-approval pharmacovigilance surveillance. It also may be useful to better communicate the safety data obtained with use of biosimilars in Europe, where there have been more than 400 million patient-days of experience in which no new immunogenicity concerns have been observed .
Preferred Information Sources
Peer-reviewed literature is by far the most trusted and preferred information source for biosimilars among physicians (82%; Fig. S6 in Supplementary Materials). The top trusted information sources include scientific journals (88%), FDA (73%), and physician peers (64%); however, dermatologists and rheumatologists indicated less trust in the FDA as an information source compared with other specialties at 64% and 58%, respectively (Fig. S7 in Supplementary Materials). Physician trust in media was very low across all specialties (<5%). Journals, physician peers, and congresses/symposia are the primary trusted information sources for current information on biosimilars across specialties.
Physician Interests and Overall Thoughts
The results of this survey highlight a significant need for evidence-based education about biosimilars for physicians across specialties. Although the vast majority of physicians have heard about biosimilars, their actual knowledge of the fundamentals of biosimilars was low, as the portion of respondents answering correctly rarely surpassed 50% for questions that focused on key aspects of these therapies.
Five major knowledge gaps were identified: defining biologics, biosimilars and biosimilarity; understanding the approval process and the use of “totality of evidence” to evaluate biosimilars; understanding that the safety and immunogenicity of a biosimilars are comparable to the originator biologic; understanding the rationale for extrapolation of indications; and defining interchangeability and the related rules regarding pharmacy-level substitution. With respect to future educational efforts, peer-reviewed literature is by far the most trusted and preferred information source for biosimilars among specialty physicians.
Although physicians across specialties have generally positive attitudes toward biosimilars, dermatologists and rheumatologists appear to be less enthusiastic about biosimilars, particularly due to safety concerns. These physician groups may require more information from trusted sources to address their current concerns.
This survey provides a baseline of of the knowledge level of physicians about biosimilars. A similar survey will be repeated in 2–3 years time to monitor changes.
Biosimilar Definitions 
A BIOSIMILAR MEDICINE is a biologic that is highly similar to an FDA-approved biological medicine, known as an originator biologic. A biosimilar must be (1) highly similar to the originator biologic notwithstanding minor differences in clinically inactive components, and (2) have no clinically meaningful differences in safety or effectiveness compared to the originator biologic
An INTERCHANGEABLE BIOLOGIC is a biosimilar that has been demonstrated to produce the same clinical result as its originator biologic in any given patient. In addition, for a product that is administered multiple times to an individual, the risk in terms of safety or diminished efficacy of alternating between use of the interchangeable biologic and its originator biologic is not greater than the risk of using the originator biologic alone. Designation of interchangeability requires additional supporting evidence, which will be further defined by the FDA
An interchangeable biologic may be substituted by a pharmacist for the originator biologic or vice versa without the intervention of the healthcare professional who wrote the prescription. State laws govern the substitution process, and communication to the healthcare provider who wrote the prescription may be required after the product is dispensed
EXTRAPOLATION is the process by which a biosimilar may be approved for one or more indications for which its reference biological product is licensed but for which there was no head-to-head clinical comparison. This approval is based on the extrapolation of the totality of data obtained with the biosimilar molecule in direct comparison to the originator biologic. Every indication for which extrapolation is sought must be scientifically justified
The design, execution, analysis, and article processing charges were funded by the Biosimilars Forum, Washington, DC, USA. The founding members of the Biosimilars Forum represent the majority of companies with the most significant US biosimilars development portfolios, including: Allergan, Amgen, Boehringer Ingelheim, Coherus BioSciences, EMD Serono, Merck, Pfizer, Samsung Bioepis, Sandoz, and Teva. Amgen, Boehringer Ingelheim, EMD Serono, Merck, Pfizer and Sandoz were the Biosimilars Forum companies that contributed to this publication. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.
Geoffrey Eich of Amgen Inc. provided assistance with survey design and data analysis. Melissa Glim, Monique LaRocque and Carey Pilato of Feinstein Kean Healthcare | Ogilvy provided assistance with survey design, data analysis, and editing.
Hillel Cohen is an employee of Sandoz Inc. and owns stock in the Novartis Corp.
Donna Beydoun is an employee and stockholder of Merck, Inc.
David Chien is an employee and stockholder of Amgen Inc.
Tracy Lessor is an employee of Feinstein Kean Healthcare. She does not own stock.
Robert Popovian is an employee and stockholder of Pfizer Inc.
Dorothy McCabe is an employee of Boehringer Ingelheim, and owns stock in Pfizer Inc.
Michael Muenzberg is an employee of Ares Trading S.A. He does not own stock.
Jonathan Uy is an employee of Sandoz Inc. and owns stock in the Novartis Corp.
Compliance with Ethics Guidelines
This article does not contain any new studies with human or animal subjects performed by any of the authors.
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