Introduction

A patient information leaflet (PIL) is a document that provides detailed information for patients or caregivers on the use, administration, risks, storage, and disposal of a medicine. It is commonly printed on paper and inserted in or attached to the product package. The information, structure, and layout vary across jurisdictions, based on a defined regulation (Refer to Annex 1).

Given that information on a printed piece of paper is static, any revisions needed to ensure the safe use and administration of a product must go through a lengthy process that is then only reflected in a newly printed version of the paper document. In addition, the need to guarantee patient safety has led to increasing regulations that require additional information and notices to be included in the PIL—often resulting in a lengthy document that is difficult to read by the patient or caregiver. For example, a recent study conducted in the United Kingdom found that 63% of the information in a paper PIL was considered difficult for older people to understand [1].

To date, paper-based leaflets have been the only formally recognized forms of delivering patient information. With the rapidly evolving technology and digital platforms available to it, why has the sector not transitioned?

Evidently, recent advancements in technology have transformed the way people access information. Between 2007 and 2017, global internet use grew from 20% of the total population to 49% [2]. At the end of 2018, 60% of the global population owned a smartphone and this is expected to further increase to 79% by 2025, primarily driven by mobile subscription growth in the Asia-Pacific region [3].

The internet serves as a rich source of health-related information. A survey conducted in Europe in 2014 across 26 566 respondents from different social and demographic groups found that 59% use the internet to search for health-related information on general health topics, specific diseases, and medical treatments and procedures [4]. Another survey conducted in 2017, including 1 509 individuals in the United States aged 18 and above, found that 57% of them accessed the internet first for health-related information compared to 32% who first sought information from doctors or physicians [5].

The shift from paper to dynamic electronic PILs or e-PILs is a first step to providing patients with the opportunity to receive up-to-date and clear information on a product and provide consumers with an avenue to regularly monitor a product’s characteristics as well as enable methods to improve readability and comprehension. Moreover, it can help facilitate communication in real-time across health care professionals, regulators, manufacturers, and patients on additional or updated information on the product.

For the purpose of this paper, we refer to dynamic e-PILs as patient information on a medical product, approved by a health authority, accessible electronically or online which have sections or information that can be opened in a screen and displayed according to the user’s preference. We qualify the term “dynamic” as e-PILs that allow for more flexibility on the presentation of its content, for example, adjustments to the format (e.g. font or image); integrated audio and video; search or dictionary functions; and any additional interactive functions to improve the presentation of information.

Adopting a dynamic e-PIL comes with various challenges, but can serve as a viable complement or solution to the difficulties faced by patients when relying on traditional paper package inserts [6]. One of the most immediate benefits of using e-labels, such as the e-PIL, is a considerable decrease in the time and resources needed to update and amend patient information, avoiding the possibility of having a marketed medicinal product with a dated package insert. The adoption of these platforms to deliver effective patient information therefore require bold changes: be it amendments to current legislation or the determination to adopt and deploy new and emerging technologies for the benefit of patients and society as a whole.

This commentary presents regulatory considerations that we believe are valuable for regulators to take into account when shifting to or adopting dynamic e-PILs and supports these with practical examples and case studies from literature reviews and the authors’ regulatory expertise and experiences.

Regulatory Considerations for the Effective Adoption of Digital Platforms

Promote a Digital Outlook and Act for Change

We believe that strong political commitment at the highest level is important in ensuring that society accepts the use of and transition to digital platforms. A clear endorsement and support to achieve this can help overcome administrative resistance and safeguard it from singular interests. For example, some international organizations and countries have developed clear guidelines and strategies that reflect their future outlook with regard to digital platforms (Box 1).

Review and Streamline

Regular review is necessary to ensure that regulations are suited to the current technological developments; encourage innovation; and, more importantly, ensure that safe, efficacious, and quality medicinal products are received by the patients in a timely manner (Box 2).

Furthermore, overlapping regulations should be streamlined to ensure that any newly introduced or updated requirements do not contradict with existing standards at a national and, if applicable, at a regional level to ensure that there is a harmonized approach in the use of digital platforms.

Set Minimum Requirements and Encourage Flexibility in Implementation

Countries may propose and set minimum requirements on the adoption of digital e-PILs or digital platforms in general. By setting minimum requirements, countries may adopt aligned principles without being overly prescriptive while ensuring patient adherence and safety. A set of proposed principles are presented in Box 3.

Contemporary or digital platforms provide the opportunity to increase product information utility and value-add; however, a flexible approach must be adopted when deciding to transition to dynamic e-PILs. Dynamic e-PILs can be introduced on a voluntary basis—considering them as a complement, rather than an ultimate alternative to physical PILs inserted in the package. Countries could adopt dynamic e-PILs as a default medium, and offer paper-based options as and when appropriate. This permits the possibility of transitioning towards paperless information, without undermining current rules and regulations (Box 4).

Staging the transition would be essential in allowing a certain period for countries to be sufficiently informed or master digital media. In 2017, the Asia-Pacific Economic Cooperation (APEC) came up with a set of best practices for electronic labelling and underscored various e-labelling policy development stages and recommended actions (Table 1).

Table 1. e-Labelling Policy Development Stages.
Full size table

Ensure Transparent Stakeholder Engagement and be Patient-Centric When Designing Platforms

Stakeholder engagement ensures that the adoption of new or updated regulations or platforms is effective and feasible. We refer to stakeholders as all relevant parties that should be involved, including but not limited to regulators, industry, health technology assessors, payers, health care professionals, and patients. Making ideas or projects transparent and open for discussion to stakeholders throughout the project helps in preparing stakeholders in meeting new requirements and processes.

Part of ensuring stakeholder engagement is embracing patient-centric approaches. Gaining insights and perspectives from patients and empowering them in the process would help transform dynamic e-PILs to their benefit, as it becomes designed to suit their needs and preferences.

For this reason, we believe that a PIL is considered effective when it is read, understood, retained, and adhered to by the patient or caregiver. While a physical PIL may provide a standard approach to presenting information, it may not provide the flexibility to ensure that the information included is suitable and effective to the reader. Numerous studies have been made to judge a patient’s reactions to the PIL’s structure, format, and content based on regulatory guidelines, and have found certain formats and structure often illegible to the reader [14,15,16,17] (Box 5).

While it is important to ensure that the information included in the e-PIL is suitable to the patient, other initiatives to improve digital health literacy or the patient’s understanding of the information online can also encourage more patient-centric approaches and foster patient engagement (Box 6).

Guarantee Access, Availability, and Security

Ensuring access and availability of the information and digital platform is important when transitioning to the dynamic e-PIL. This entails guaranteeing that the patients know how and where to find the needed information on the medical product, and creating sufficient awareness on the platform’s availability.

When it comes to accessing information, this can be made through a single country-specific platform such as DailyMed in the United States or Fass.se in Sweden or through the manufacturer’s website. Quick response (QR) codes and barcode scanning are increasingly becoming commonplace—allowing patients or consumers to link information quickly on a product’s information through a mobile phone. In 2018, the European Medicines Agency (EMA) introduced a set of general principles of acceptability and rules of procedure to encourage the use of mobile scanning and other technologies for this purpose [18].

While guaranteeing access is essential, it is beneficial for society to ensure that its citizens receive the best, updated information on a medicinal product, which is available. Therefore, guaranteeing security of the information and limiting the access to modifications between the regulator and the manufacturer must be considered.

Support Common Frameworks and Standards

Ensuring that patients receive consistent and high-quality information regardless of regulatory jurisdiction is an important consideration in the adoption of the dynamic e-PIL. Varying or fragmented legal frameworks often impede the inter-operability of systems and may duplicate efforts leading to the inefficient use of resources.

The Future of Patient Information

While this paper focuses on the transition and adoption of dynamic e-PILs, more tailored approaches to providing patient information are emerging. This includes increasing personalized services that are available 24/7 to guide and inform the patient on the safe use and administration of specific medicinal products. These enablers could provide for more personal and more relevant sharing of information on specific diseases or conditions. A few examples include virtual medical assistants and artificial intelligence-driven chatbots, which are increasingly becoming a resource for health information—using speech, text, audio, and video to check symptoms and connect with medical representatives, obtain product information, or receive regular reminders on medication or treatments. Setting up personal notifications tailored on individual circumstances, such as drug interactions, disease history, or child-bearing potential, could be enabled so that immediate information can be highlighted and received by the patient. As these chatbot services become increasingly used, the sector could learn from experience gained and even further improve content provided and its presentation (Box 7).

Furthermore, the increasing use of wearables and smart machines is transforming the way we monitor our health and make decisions on the medicinal products we use—whether it means adhering to its use, guaranteeing safety, or choosing the right product based on one’s health history.

Conclusion

In this paper, we presented regulatory considerations to help inform regulators when adopting the dynamic e-PIL—that is, transitioning from the traditional, common use of paper leaflet to the use of on-screen or digital platforms for more effective patient information on medicinal products, as a way of continuously guaranteeing patient safety. This transition to dynamic e-PILs or e-labelling is possible with strong political or top-down commitment, an efficient and progressive regulatory environment, a patient-oriented focus, and a harmonized and coordinated approach.

Indeed, an increasingly digital future is inevitable—society will continue to move towards the adoption of new technologies. Hence, as knowledge and development in these areas progresses, we must persevere to ensure that no patient gets left behind.