To date, no consensus exists among stakeholders about switching patients between reference biological products (RPs) and biosimilars, which may have been curbing the implementation of biosimilars in ...clinical practice. This study synthesizes the available data on switching and assesses whether switching patients from a RP to its biosimilar or vice versa affects efficacy, safety, or immunogenicity outcomes. A total of 178 studies, in which switch outcomes from a RP to a biosimilar were reported, was identified. Data were derived from both randomized controlled trials and real‐world evidence. Despite the limitations stemming from a lack of a robust design for most of the studies, the available switching data do not indicate that switching from a RP to a biosimilar is associated with any major efficacy, safety, or immunogenicity issues. Some open‐label and observational studies reported increased discontinuation rates after switching, which were mainly attributed to nocebo effects. Involvement of the prescriber in any decision to switch should remain and attention should be paid to the mitigation of a potential nocebo effect.
Background
Despite the benefits offered by biosimilars in terms of cost savings and improved patient access to biological therapies, and an established regulatory pathway in Europe, biosimilar ...adoption is challenged by a lack of knowledge and understanding among stakeholders such as healthcare professionals and patients about biosimilars, impacting their trust and willingness to use them. In addition, stakeholders are faced with questions about clinical implementation aspects such as switching.
Objective
This study aims to provide recommendations on how to improve biosimilar understanding and adoption among stakeholders based on insights of healthcare professionals (physicians, hospital pharmacists, nurses), patient(s) (representatives) and regulators across Europe.
Method
The study consists of a structured literature review gathering original research data on stakeholder knowledge about biosimilars, followed by semi-structured interviews across five stakeholder groups including physicians, hospital pharmacists, nurses, patient(s) (representatives) and regulators across Europe.
Results
Although improvement in knowledge was observed over time, generally low to moderate levels of awareness, knowledge and trust towards biosimilars among healthcare professionals and patients are identified in literature (
N
studies = 106). Based on the provided insights from interviews with European experts (
N
= 44), a number of challenges regarding biosimilar stakeholder understanding are identified, including a lack of practical information about biosimilars and their use, a lack of understanding about biosimilar concepts and a lack of knowledge about biologicals in general. Misinformation by originator industry is also believed to have impacted stakeholder trust. In terms of possible solutions and actions to improve stakeholder understanding, broad support exists to (1) organize initiatives focussed on explaining the rationale behind biosimilar concepts and the approval pathway, (2) invest in education about biologicals in general, (3) develop clear and one-voice regulatory guidance about biosimilar interchangeability and switching across Europe, (4) disseminate real-world clinical biosimilar (switch) data, (5) share biosimilar experiences by key opinion leaders and among peers, (6) provide practical biosimilar product information, (7) provide guidance about biosimilar use, (8) actively counterbalance misinformation and organize information initiatives by neutral entities, (9) organize multi-stakeholder informational and educational efforts, aligning information between involved stakeholder groups and (10) design initiatives in a way that ensures active information uptake. Furthermore, interviewees argue that governments should be proactive in these regards.
Conclusions
This study argues in favour of a structural, multi-stakeholder framework at both European and national level to improve stakeholder biosimilar understanding and acceptance. It proposes a number of actionable recommendations that can inform policy making and guide stakeholders, which can contribute to realizing healthcare system benefits offered by biosimilar competition.
Electronic informed consent (eIC) may offer various advantages compared to paper-based informed consent. However, the regulatory and legal landscape related to eIC provides a diffuse image. By ...drawing from the perspectives of key stakeholders in the field, this study aims to inform the creation of a European guidance framework on eIC in clinical research.
Focus group discussions and semi-structured interviews were conducted with 20 participants from six stakeholder groups. The stakeholder groups included representatives of ethics committees, data infrastructure organizations, patient organizations, and the pharmaceutical industry as well as investigators and regulators. All were involved in or knowledgeable about clinical research and were active in one of the European Union Member States or at a pan-European or global level. The framework method was used for data analysis.
Stakeholders underwrote the need for a multi-stakeholder guidance framework addressing practical elements related to eIC. According to the stakeholders, a European guidance framework should describe consistent requirements and procedures for implementing eIC on a pan-European level. Generally, stakeholders agreed with the definitions of eIC issued by the European Medicines Agency and the US Food and Drug Administration. Nevertheless, it was raised that, in a European guidance framework, it should be emphasized that eIC aims to support rather than replace the personal interaction between research participants and the research team. In addition, it was believed that a European guidance framework should include details on the legality of eIC across European Union Member States and the responsibilities of an ethics committee in the eIC assessment process. Although stakeholders supported the idea to include detailed information on the type of eIC-related materials to be submitted to an ethics committee, opinions varied on this regard.
The creation of a European guidance framework is a much needed factor to advance eIC implementation in clinical research. By collecting the views of multiple stakeholder groups, this study advances recommendations that may facilitate the development of such a framework. Particular consideration should go to harmonizing requirements and providing practical details related to eIC implementation on a European Union-wide level.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Over the years, there has been increasing interest in electronic informed consent (eIC) in clinical research. The user-friendliness of an eIC application and its acceptance by stakeholders plays a ...central role in achieving successful implementation.
This study aims to identify insights for the design and implementation of a user-friendly, personalized, and long-term eIC application based on a usability study with (potential) research participants and semistructured interviews with stakeholders on the practical integration of such an application into their daily practice.
An eIC prototype was evaluated and refined through usability testing among Belgian citizens and iterative redesign. On the basis of a digital literacy questionnaire, a heterogeneous sample of participants was established. Participants needed to complete a series of usability tasks related to personalization and long-term interaction with the research team while using the "think aloud" technique. In addition, usability tests involved completing the System Usability Scale questionnaire and taking part in a semistructured feedback interview. Furthermore, semistructured interviews were conducted with ethics committee members, health care professionals, and pharmaceutical industry representatives active in Belgium and involved in clinical research. Thematic analysis was undertaken using the NVivo software (Lumivero).
In total, 3 iterations of usability tests were conducted with 10 participants each. Each cycle involved some participants who reported having low digital skills. The System Usability Scale scores related to the tasks on personalization and long-term interaction increased after each iteration and reached 69.5 (SD 8.35) and 71.3 (SD 16.1) out of 100, respectively, which represents above-average usability. Semistructured interviews conducted with health care professionals (n=4), ethics committee members (n=8), and pharmaceutical industry representatives (n=5) identified the need for an eIC system that can be easily set up. For example, a library could be established enabling stakeholders to easily provide background information about a clinical study, presented in the second layer of the interface. In contrast, some functionalities, such as informing participants about new studies through an eIC system, were not considered useful by stakeholders.
This study provides insights for the implementation of a user-friendly personalized and long-term eIC application. The study findings showed that usability testing is key to assessing and increasing the user-friendliness of an eIC application. Although this eIC system has the potential to be usable by a wide audience, participants with low digital literacy may not be able to use it successfully, highlighting the need for additional support for participants or other alternatives to an eIC system. In addition, key lessons emerging from the interviews included ensuring that the application is easy to implement in practice and is interoperable with other established systems.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background:
By improving the affordability and accessibility of biologicals, biosimilar competition provides important benefits to healthcare systems and patients. In Belgium, biosimilar uptake and ...competition is limited compared to other European markets. Whereas other countries have initiated structured biosimilar introduction or switching plans, no such framework or guiding principles are yet available in Belgium.
Objective:
This study aims to develop recommendations that can inform policy action in Belgium on biosimilar use, especially in the context of switch decision-making, and this by drawing from the perspectives of healthcare professionals involved in procuring, prescribing, switching and dispensing biologicals including biosimilars.
Methods:
This study made use of the consensus-building Nominal Group Technique, consisting of a three-step process 1) individual grading, 2) three structured Focus Group Discussions, 3) final individual grading involving an expert group of Belgian healthcare professionals (physician specialists and hospital pharmacists).
Results:
Participants (
n
= 13) voiced challenges with the use of biosimilars and switching in practice, and a lack of incentives to use them. Six concrete areas for policy development to support stakeholders with biosimilar use and switch decision-making were identified: 1) address stakeholder hesitations regarding (multiple) switching, 2) provide meaningful incentives, 3) guide healthcare professionals with product decision-making, 4), align practical product modalities when possible, 5) involve healthcare professionals in policy making, and 6) provide practical switch support and patient information material, particularly in the ambulatory care setting. For each area, specific consensus-based recommendations were developed. Furthermore, a set of switch management and patient communication principles was derived, including amongst others, generating buy-in from involved stakeholders prior to switching and communicating with a one-voice message.
Conclusion:
Without cohesive actions to reduce hurdles and without tangible benefits or steering mechanisms, changes in biosimilar use are unlikely in Belgium. To overcome this and stimulate market competitiveness, this study advances a set of concrete policy recommendations. At large, policy makers should develop an integrated policy framework, with a pro-active, best-value biological implementation roadmap that provides guidance and compelling measures to incentivize healthcare professionals to use biosimilars. Particular consideration should go to the ambulatory care setting, since drivers for biosimilar use are quasi absent in this context.
Background: In Europe, off-patent biologicals and biosimilars are largely procured by means of tender procedures. The organization and design of tenders may play a key role in the evolving biosimilar ...market, and currently, it is not fully elucidated how tenders for off-patent biologicals and biosimilars are designed and if approaches are aligned with sustaining market competition and societal savings for healthcare systems over the long term. This study aims to (i) explore the design and implementation of tender procedures for off-patent biologicals and biosimilars in Europe, (ii) identify learnings for sustainable tender approaches from purchasers and suppliers, and (iii) formulate recommendations in support of competitive and sustainable tender practices in the off-patent biologicals market. Methods: A mixed methods design was applied. A quantitative web-survey was conducted with hospital pharmacists and purchasers (N = 60, of which 47 completed the survey in full), and qualitative expert-interviews with purchasers and suppliers (N = 28) were carried out. Results: The web survey results showed that the organization and design of tenders for off-patent biologicals and biosimilars, and the experience of hospital pharmacists and purchasers with this, considerably varies on several elements across European countries. From the qualitative interviews, signals emerged across the board that some of the current tender approaches might negatively affect market dynamics for off-patent biologicals and biosimilars. The focus on generating short-term savings and existence of originator favouring tender practices were identified as elements that may limit timely competition from and market opportunity for biosimilar suppliers. The need to optimize tender processes, considering a more long-term strategic and sustainable view, was expressed. In addition, challenges appear to exist with differentiating between products beyond price, showing the need and opportunity to guide stakeholders with the (appropriate) inclusion of award criteria beyond price. Due to the variety in tender organization in Europe, a ‘one size fits all’ tendering framework is not possible. However, on an overarching level, it was argued that tender procedures must aim to (i) ensure market plurality and (ii) include award criteria beyond price (warranted that criteria are objectively and transparently defined, scored and competitively rewarded). Depending on the market (maturity), additional actions may be needed. Conclusions: Findings suggest the need to adjust tender procedures for off-patent biologicals and biosimilars, considering a more long-term strategic and market sustainable view. Five main avenues for optimization were identified: (i) safeguarding a transparent, equal opportunity setting for all suppliers with an appropriate use of award criteria; (ii) fostering a timely opening of tender procedures, ensuring on-set competition; (iii) ensuring and stimulating adherence to laws on public procurement; (iv) securing an efficient process, improving plannability and ensuring timely product supply and (v) safeguarding long-term sustainable competition by stimulating market plurality.
Biosimilar medicines have been on the European market for 15 years. Despite the extensive and positive experience with biosimilars across Europe, their uptake remains limited in Belgium. One of the ...possible factors limiting uptake in clinical practice is the inadequate understanding and lack of trust in biosimilars among patients. This study aimed to assess the level of knowledge and perceptions about biosimilar medicines among Belgian patients in the ambulatory care.
This study consisted of online questionnaires among Belgian patients in the ambulatory care (i.e., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn's disease, ulcerative colitis, diabetes mellitus type I and II). The results were collected between December 2020 and February 2021. The data were analyzed with descriptive and inferential statistics.
In total, 657 patients across all disease areas of interest participated in this study. Only 38% of patients had heard of biosimilars before. Of those patients, most (58%) were aware that biosimilars are as safe and effective as their reference product. The vast majority of respondents (68%) would agree with transitioning to a biosimilar if their physician prescribed it, only 3% would never agree with a transition to a biosimilar. If a physician would propose to change their current originator biological therapy with its biosimilar, nearly all patients (95%) want their physician to explain the decision and inform them. For additional information about biosimilars, Belgian patients prefer brochures or folders (41%), or available resources on the internet (35%). Physicians were indicated as the preferred source of information (95%), followed by pharmacists (51%), academia (39%), and patient associations (35%). Most patients require information regarding the safety and efficacy (78%), price and reimbursement (64%), and the clinical development process (56%) of the biosimilar.
Belgian patients require information about biosimilar medicines. However, most patients are open and positive towards transitioning their current biological therapy with its biosimilar if sufficiently supported by their healthcare providers.
Beyond evaluation and approval, European and national regulators have a key role in providing reliable information on biosimilars and the science underpinning their development, approval, and use.
...This study aims to (i) review biosimilar information and guidance provided by EMA and national medicines agencies and (ii) explore stakeholder perspectives on the role of regulators in enabling acceptance and use of biosimilars.
This study consists of (i) a comparative review of regulatory information and position statements across medicine agencies (
= 32) and (ii) qualitative interviews with stakeholders in Europe (
= 14).
The comparative analysis showed that regulatory information and guidance about biosimilars offered by national medicines agencies in Europe varies, and is limited or absent in multiple instances. Approximately 40% (13/31) of the national medicines agencies' websites did not offer any information regarding biosimilars, and for about half (15/31) no educational materials were provided. Only less than half of national medicines agencies provided guidance on biosimilar interchangeability and switching (8/31 and 12/31, respectively). Among the national medicines agencies that did offer guidance, the extent (e.g., elaborate position vs. brief statement) and content (e.g., full endorsement vs. more cautious) of the guidance differed substantially. Countries that have a strong involvement in EU level biosimilar regulatory activities generally had more elaborate information nationally. Interviewees underwrote the need for (national) regulators to intensify biosimilar stakeholder guidance, especially in terms of providing clear positions regarding biosimilar interchangeability and switching, which in turn can be disseminated by the relevant professional societies more locally.
This study revealed that, despite strong EU-level regulatory biosimilar guidance, guidance about biosimilars, and their use differs considerably across Member States. This heterogeneity, together with the absence of a clear EU-wide position on interchangeability, may instill uncertainty among stakeholders about the appropriate use of biosimilars in practice. Regulators should strive for a clear and common EU scientific position on biosimilar interchangeability to bridge this gap and unambiguously inform policy makers, healthcare professionals, and patients. Furthermore, there is a clear opportunity to expand information at the national level, and leverage EU-developed information materials more actively in this regard.
Background:
Countries are struggling to provide affordable access to medicines while supporting the market entry of innovative, expensive products. This
Perspective
aims to discuss challenges and ...avenues for balancing health care system objectives of access, affordability and innovation related to medicines in Belgium (and in other countries).
Methods:
This
Perspective
focuses on the R&D, regulatory approval and market access phases, with particular attention to oncology medicines, precision medicines, orphan medicines, advanced therapies, repurposed medicines, generics and biosimilars. The authors conducted a narrative review of the peer-reviewed literature, of the grey literature (such as policy documents and reports of consultancy agencies), and of their own research.
Results:
Health care stakeholders need to consider various initiatives for balancing innovation with access to medicines, which relate to clinical and non-clinical outcomes (e.g. supporting the conduct of pragmatic clinical trials, treatment optimisation and patient preference studies, optimising the use of real-world evidence in market access decision making), value assessment (e.g. increasing the transparency of the reimbursement system and criteria, tailoring the design of managed entry agreements to specific types of uncertainty), affordability (e.g. harnessing the role of generics and biosimilars in encouraging price competition, maximising opportunities for personalising and repurposing medicines) and access mechanisms (e.g. promoting collaboration and early dialogue between stakeholders including patients).
Conclusion
: Although there is no silver bullet that can balance valuable innovation with affordable access to medicines, (Belgian) policy and decision makers should continue to explore initiatives that exploit the potential of both the on-patent and off-patent pharmaceutical markets.
Changes in the clinical trials landscape have been driven by advancements in digital technology. The use of electronic informed consent to inform research participants and to obtain their consent ...electronically has the potential to improve participant-researcher interactions over time, facilitate clinical trial participation, and increase efficiency in clinical trial conduct. A personalized electronic informed consent platform that enables long-term interactions with the research team could function as a tool to empower participant engagement in clinical trials. However, significant challenges persist impeding successful and widespread implementation. This Perspective provides insights into the opportunities and challenges for the implementation of electronic informed consent in clinical trials. It sets out key recommendations to promote the implementation of this innovative approach to the informed consent process, including the creation of uniform electronic informed consent platforms at regional and national level.
PDF
