Introduction

A regulated market is “a business controlled by government rules, laws and requirements” (Schiavone & Simoni, 2019). Firms can refer to rules as a source of creativity or comply with them (Blind, 2016). Regulated markets have the aim of establishing uniformity in transactions through the enforcement of explicit norms (Woodward & Kaiser, 2002; Greif & Kingston, 2011). The functions and methods employed by these organizations have evolved, leading to more stringent and precise regulations (Woodward & Kaiser, 2002). When it comes to the financial domain, regulated and unregulated markets diverge primarily in terms of the governing laws rather than the types of assets being traded (Ferreira & Sandner, 2021; Lee, 1998).

Although there are policy incentives encouraging investment in R&S, the regulatory environment may affect how corporations approach innovation in a highly regulated context (Jin et al., 2019; Hashmi & Alam, 2019). Highly regulated industries have entry barriers that make it challenging to introduce innovation (Gopal et al., 2019). The health sector is significantly impacted by regulatory pressure, specifically regarding the market access of innovative products (van de Bovenkamp et al., 2020). To illustrate this point, Schiavone and Simoni (2019) identified three primary obstacles to the adoption of innovation in healthcare: (1) the diversity of actors and evaluation standards, (2) a restricted ability to assess the impact of innovation on the entire healthcare value chain, and (3) uncertainty regarding the timing of adoption decisions.

The literature widely addressed the potential impact of regulation on the innovation process (Amable et al., 2016; Blind et al., 2017; Markman et al., 2019; Schiavone & Simoni, 2019). Regulations can be related to various economic, social, and institutional sources (Blind, 2016; Marino et al., 2019). According to Blind (2016), economic regulation can impact the competitive dynamics within the market, thereby motivating companies to invest in innovation as a means of ensuring their survival. This type of regulation can influence pricing mechanisms and the oversight of public utilities. Consequently, the implementation of policies related to economic regulation may have either positive or negative effects on innovation. Furthermore, the author defines social regulation as being specific to sectors. For instance, as Magistretti et al. (2021) attested, the pharmaceutical industry norms are more complex, impacting the entry of products into the market. As Donaldson and Preston (1995, p. 65) stated, “The idea that companies have stakeholders has become commonplace in management literature, both academic and professional”. Stakeholder management is an essential success factor in innovation projects (Elias, 2016; Fliaster & Kolloch, 2017). This is evident in highly regulated markets (Mukundhan & Nandakumar, 2016). As previously stated, a significant obstacle to the implementation and acceptance of innovation within the healthcare industry is the existence of several actors with varying interests (Yu & Li, 2020). Companies seeking to promote their products must engage with multiple actors and organizations that possess distinct institutional roles, resulting in a complex and unpredictable process of gaining market access (Schiavone & Simoni, 2019).

However, existing studies still need to be more comprehensive and complete, and none of them analyses the strategies to shorten the entry of innovation in the market under regulation pressure situations (Gopal et al., 2019; Amable et al., 2016; Blind et al., 2017; Schiavone & Simoni, 2019; Markman et al., 2019; Jin et al., 2019; Hashmi & Alam, 2019). Most of these empirical studies are limited to the role of normative frameworks as a source of firms’ legitimacy (Suchman, 1995) by creating positive results in terms of market survival and positioning (Bossle et al., 2016).

This background forms the basis to explore the topic of this research, namely, how institutional actors contribute to shortening the entry of innovation in the market in highly regulated contexts, particularly within service industries such as pharmaceuticals using Early Access programs. Our research question is, How do institutional actors push the entry of innovation in highly regulated markets? In the pharmaceutical sector, National drug agencies represent the main institution influencing access to the market of innovative products. Thus, this paper aims to investigate which are the main strategies to foster the commercialization of innovative drugs in three different countries. This research extends the knowledge in the innovation field (Adams et al., 2006; Goffin & Mitchell, 2017; Frishammar et al., 2019) by analyzing the main strategies to shorten the entry of innovation in highly regulated markets by offering theoretical and practical insights.

This study aims to contribute to the innovation management literature by offering an inductive conceptual framework based on three characterizing dimensions: (1) authorities involved, (2) eligibility criteria and (3) applicant to analyze the different configurations of Early Access strategies. In the management field, this topic is still in its infancy. This contribution offers a new perspective on Early Access’s role in the entry of innovation into the market (Thomas & Maine, 2019), focusing on service industries such as the pharmaceutical industry (Jommi et al., 2021; Schiavone & Simoni, 2019). To tackle the research question, an analysis of innovation management in the pharmaceutical industry was conducted using a multiple-case study method. An inductive conceptual framework demonstrates that different factors affect the Early Access programs’ configuration.

The paper is structured as follows. Literature review section reviews the relevant literature on diffusion innovation and market entry strategy in highly regulated markets. Method section describes the research methodology, including the case study analysed and the research structure. Findings section provides analysed and discussed results in the next section, Discussion. In the latter section, we also show implications for academics, practitioners and policymakers. Finally, the limitations of the analysis and several ideas for future research are outlined.

Literature review

Innovation in a highly regulated context

Innovation is “a multi-stage process by which organisations transform ideas into new/improved products, services or processes to advance, compete and differentiate successfully in the marketplace” (Baregheh et al., 2009, p. 1334). Innovation offers an opportunity to solve challenging situations, as seen in the mining industry where accessing difficult deposits often necessitates new technologies (Deloitte, 2016; Gruenhagen & Parker, 2020; Vargo et al., 2020). Various theoretical foundations have been applied in innovation studies. One such foundation is the institutional theory, which views the market as an organizational field where rules influence actors’ behaviors (Branstad & Solem, 2020; Donbesuur et al., 2020; Storbacka, 2019). Firms seek “legitimacy” to survive and it is achieved when a social actor adheres to the formal and informal rules of the institution (Suchman, 1995).

OECD (1997) defines regulation as “the implementation of rules by public authorities and governmental bodies to influence market activity and the behavior of private actors in the economy”. Highly regulated markets are characterized by stringent government control, requiring companies to adhere to industry standards, conventions, and procedures (Bossle et al., 2016). High regulation impacts organizations’ activities, including communication, marketing strategies, and competition, creating opportunities and limitations for innovation (Markman et al., 2019; Schiavone & Simoni, 2019). Based on this assumption, the regulatory context influences firms’ innovation process (Jin et al., 2019; Hashmi & Alam, 2019).

Companies struggle to comprehend the institutional framework due to the necessity of adhering to the norms set by various players. As a result, they try to adapt their behavior to match that of previously existing market organizations (Parente et al., 2019). For instance, the food industry is one of the main sectors affected by mandatory standards regarding product quality and safety (Aday & Aday, 2020). Moreover, these standards significantly impact manufacturers’ income and market access (Mohan, 2020).

As Blind (2016) attested the regulatory framework’s effect is sector-specific. For example, in the automobile industry, environmental standards improve firms’ competitiveness by aligning products with consumer needs (Luthra et al., 2016). Conversely, empirical evidence highlights that stringent regulations decrease the market introduction of new drugs in the pharmaceutical industry (Paolone et al., 2022). It is hard to conclusively determine the impact of the regulatory framework on innovation. As already said, empirical evidence offers a heterogeneous picture of the sector, the type of innovation, and the timing of the impact (Blind et al., 2017).

As mentioned above, the pharmaceutical industry and healthcare, are profoundly influenced by the regulatory framework (Brem et al., 2021; Leite et al., 2020; Sultana et al., 2020). According to Länsisalmi et al. (2006), innovation in healthcare is “the intentional introduction and application within a role, group, or organization of ideas, processes, products, or procedures new to the relevant unit of adoption, designed to significantly benefit the individual, the group, or wider society”. Pharmaceutical innovation aims to provide organizations with advanced tools to create new value for patients, caregivers, and payers of pharmaceutical services (Aldieri et al., 2020). To achieve this, pharmaceutical businesses should revise their strategies (Elton & O'Riordan, 2016). The National Institutes of Health also play a critical role in promoting market access to new drugs by funding basic public research (Aldieri et al., 2020).

The regulatory framework influences market entry in terms of timing (Markman et al., 2019).

Stringent standards can delay the availability of products for consumers, giving rise to the term “Early Access”. This concept, originally from the video games industry, refers to “a software release strategy that allows consumers to purchase an unfinished version of the software” (Lin et al., 2018). Early Access has become widely used in the pharmaceutical industry (Jommi et al., 2021; Tomino et al., 2017; Costa & Magrini, 2022). From a market access perspective, the patient access process is complex, multifaceted, and time-consuming (Tomino et al., 2017). Patients may suffer severe consequences due to the lengthy procedure from European approval to the drug’s availability for Italian patients, particularly for novel medications (AIOM, 2019). The regulatory system has revised its approach to expedite the assessment and approval of medications for treating severe and rare disorders (Costa & Magrini, 2022). The need to ensure faster access to drugs for patients has led to the emergence of Early Access programs (Jommi et al., 2021).

Early Access programs are “a set of provisions regulating access to and prescription of EMA-approved drugs “before” reimbursement by the National Health Service” (AIOM, 2019). Making these procedures efficient is essential to guarantee that the correct patient can access the right medicine at the right time (Tomino et al., 2017). It is crucial to offer tools that allow faster market entry for innovative products in highly regulated sectors (Schiavone & Simoni, 2019). Addressing customers' demands and expectations promptly enhances their satisfaction and loyalty (Cobelli & Chiarini, 2020).

Method

To tackle our research question, we use the multiple case study method as a research approach (Eisenhardt, 1989; Yin, 2013) to define a model regarding the configuration of Early Access programs in the pharmaceutical industry. The market access to new drugs is heterogeneous across countries. Thus, we conducted a cross-national analysis exploring Early Access programs in Italy, France and the UK to highlight national differences and similarities. The multiple-case approach allows for more accuracy and generalisability, facilitating the replicability of the results (Saunders et al., 2007). Additionally, it is a valuable method for investigating complex phenomena (Eisenhardt, 1989; Yin, 1994), focusing on the social processes involved (Eisenhardt & Graebner, 2007; Greenwood & Suddaby, 2006).

Early Access programs: a comparative analysis between Italy, France and the UK

The study was located in the pharmaceutical industry, which in Europe is regulated by a set of norms about the new products’ access to the market (Schiavone & Simoni, 2019). Regulatory pressure in the pharmaceutical sector is very high, especially when introducing innovation. It is the most regulated within the manufacturing industry because of the importance of medicines to public health and because, in most countries, the public sector is the pharmaceutical industry's primary customer. A wide range of actors influences the acceptance and commercialisation of a new medical device or drug. They can significantly affect whether new products succeed or fail. New drugs’ innovativeness is based on their value in the treatment (Determ. 1535/2017, Agenzia Italiana del Farmaco), considering three main dimensions: unmet therapeutic need, added therapeutic value and quality of evidence provided (Jommi et al., 2019). Particularly, stringent norms about access to innovative products in the market affect the timing of availability to the patients. An average period of 14 months in Italy is estimated compared to 11 months in Germany, France, Spain, the UK and Switzerland (Farmindustria, 2022). Improving the availability of authorised medicines in the European Union (EU) is a crucial priority for the European drug regulatory network and the pharmaceutical industry (Newton et al., 2022). In this context, the issue of “Early Access” emerges (Löblová et al., 2019). As stipulated in EC Regulation No. 726/2004, accelerated assessment procedures reserved for medicines of the most significant therapeutic interest should be established to meet patients’ needs while considering technological progress. Implementing Regulation No. 726/2004, the European Medicines Agency (EMA) has therefore adopted a more widespread use of authorisation procedures, such as Conditional Marketing Approval (CMA) and UnderExceptional Circumstances (UEC) approval (Cavaleri et al., 2021; Villa et al., 2019).

Early access in Italy

In Italy, the Early Access system needs to be more cohesive. When it comes to drug availability, Italy ranks fifth, with 79% of products approved by the EMA. However, in terms of market access times, Italy is less efficient, ranking 14th with an average of 418 days. After receiving European approval, the average length of the approval process in Italy is 258 days. At the national level, AIFA (Agenzia Italiana del Farmaco) is responsible for assessing the therapy's position in the Italian context, considering factors such as cost-effectiveness ratio and the sustainability of the National Health System. Subsequently, for reimbursement, drugs authorized at the European level go through a negotiation procedure with AIFA, where the price and reimbursement dossier (P&R) is presented. Finally, AIFA’s Board of Directors ratifies the decision, and the Price and Reimbursement Determination is published in the Government Gazette. Further evaluation at the regional level is required for the drug to become accessible to patients.

Early access in France

In 2021, France reformed its Early Access programs, adopting a more systematic approach and establishing a dedicated fund for Early Access. The government has implemented stringent selection criteria and conducts financial impact assessments. If the funding limits are exceeded, the industry is required to reimburse the excess funds. In terms of drug availability, France ranks seventh, with 63% of products approved by the European Medicines Agency (EMA). However, when it comes to market access times, France ranks 21st, with an average of 527 days. At the national level, the Transparency Commission (TC) of HAS (Haute Autorité de Santé) conducts a health technology assessment to determine the drug's eligibility for reimbursement. The TC provides ratings based on the medical benefits and therapeutic improvements of the new product. Subsequently, prices are negotiated with the Economic Committee of Health Products (CEPS), considering the level of added benefit and the economic opinion of the Economic and Public Health Committee (CEESP). The reimbursement rate is determined by the National Health Insurance Agency (Caisse Nationale d'Assurance Maladie) primarily, and the final price is approved by the Ministry of Health.

Early access in the UK

The UK has set very high standards for authorization and has implemented a lengthy process. The Early Access to Medicines Scheme (EAMS) was launched in 2014, allowing patients with life-threatening illnesses to access medicines that have yet to be authorized. In terms of drug availability, England ranks sixth, with 72% of products approved by the EMA. However, when it comes to market access times, England ranks seventh, with an average of 335 days. The Medicines and Healthcare Products Regulatory Agency (MHRA) issues a scientific opinion on the benefit/risk equilibrium of the medicine based on the available information. Subsequently, the MHRA publishes a Public Assessment Report (PAR) and the EAMS treatment protocol. Updates are required every three months by the MHRA.

Research structure

Through a qualitative research approach, we used multiple sources of evidence to triangulate data (Eisenhardt, 1989; Yin, 2017). We collected information from the following source:

  1. 1.

    Experts’ public declarations from the specialized press and media;

  2. 2.

    Archival records – provided by the official website of National pharmaceutical agencies;

  3. 3.

    Online documentation includes reports and statistical data (Table 1).

Table 1 Source of evidence
Full size table

The analysis practised an inductive approach. In line with Bansal et al. (2018), it is appropriate in an empirical environment with little prior research. Combining multiple sources of evidence can be crucial for scholars to produce complementary perspectives of the phenomenon. Thus, experts’ public declarations, archival records and online documentation were triangulated and analysed through explorative analysis. Public declarations based on secondary sources are reliable and authoritative that directly testify to the problem (Yin, 2009) collected from statements in the press or media specialized in the pharmaceuticals sector. We selected this source based on two main questions concerning (see Table 1): (1) strategies to reduce the timing of market access to an innovative product and (2) the main characteristics of national Early Access programs. This may make the results of our analysis more robust, as these are sources that have already been validated by other authors.

Analysing the National drug agencies’ Official reports seven factors qualifying Early Access Programs in Italy, France and the UK were identified: (1) authorities involved, (2) implementation cases, (3) eligibility criteria, (4) population target, (5) indication, (6) covering drug cost and (7) applicant. Thus, the authors coded manually the data gathered following Gioia et al. (2013) method. This paper aims to identify the main factors configuring different Early Access programs. Based on the explorative analysis, the main characterizing dimensions of Early Access programs to shorten entry of innovation in a highly regulated market were defined.

Findings

The heterogeneity of market access to new drugs in pharmaceutical industries affects the configuration of Early Access programs across countries. This section presents an overview of the characteristics of various national programs to highlight similarities and differences. Based on the comparative analysis of national Early Access Programs we identify three characterizing dimensions: (1) authorities involved, (2) eligibility criteria and (3) applicant.

Early access in Italy

Our analysis highlights that Italy has shorter access times to the reimbursability list than most European countries and has activated numerous Early Access programmes. Table 2 illustrates the main characteristics of each program. Despite this, the system of early drug access is highly fragmented and characterised by instability. As affirmed in a public declaration by the Director of the Health Policy Area and Scientific Coordinator of the Pharmaceutical Observatory at Cergas, “In Italy, the EarlyAaccess system is fragmented and should be reformed with a view to the overall structuring of Early Access programmes”. The main critical aspects of these programmes are the fragmentation and sometimes operational difficulties generated, the uncertainty of the resources made available to the programs and the limited availability of data on their impact, including economic impact.

Table 2 Early Access programs in Italy
Full size table

In this vein, as detailed in a public declaration by the Head of the International Affairs Department of AIFA and Member of the Committee for Orphan Medicinal Products (Comp) of EMA, “The recipe for reducing waiting times for access to medicines is not to invent ad hoc or new procedures, but to work seriously within the existing procedures, with a greater commitment, especially on the differences and inequalities on the ground”. Additionally, in a public declaration the VP of Market Access & Government Affairs AstraZeneca attested, “Limit the differences as much as possible. Today, such a fragmented system, made up of various lists and funds, inevitably creates extreme inequalities in access times between citizens, territories and facilities”. The constant dialogue between all actors is crucial to achieving the best result in such complex issues as access to medicines. Regulatory Affairs Lead Roche in a public declaration affirmed that “Collaboration between a company and a regulatory agency can speed up drug authorisation procedures”.

Our results confirm applicants’ central role in configuring Italian Early Access programs. Different applicants characterise each programme (e.g., patient associations, regions, physicians and health companies). This confirms the abovementioned importance of involvement and collaboration between the actors involved. Additionally, central is the level of innovativeness of the drug. Indeed, one of the eligibility criteria of drugs for Early Access in the Italian context is the verification by AIFA of the innovativeness of the new product based on its value in the treatment. In this vein, it is necessary to systematise procedures, as detailed in a public declaration by Scientific Director Fondazione IRCCS Istituto Nazionale Dei Tumori di Milano, “A more systematic approach is needed, one that considers that we increasingly see drug approvals based on more and more 'engineered' studies, which allow evidence to be produced that suggests efficacy faster and faster. However, these are approvals based on preliminary data, conditional on subsequent studies. This exposes the regulatory agencies to an objective difficulty in identifying the added value of these drugs”.

Early access in France

Our analysis highlights that France has many granted Early Access programs and several patients benefiting from them. “Thanks to the Early Access programs granted, almost 70% of the experimental drugs were made available in France before FDA approval”. We can consider France a pioneer and the leader in Early Access programs. Table 3 illustrates the main characteristics of each program. The VP of Market Access & Government Affairs AstraZeneca attested in a public declaration, “The French model represents a more structured response than that available in other countries, including Italy, to a problem common to the whole of Europe. France has chosen a path to identify which pathologies or conditions need a more accelerated response and has also defined some criteria to make this system work”.

Table 3 Early Access programs in France
Full size table

As affirmed in a public declaration by the Director of the Health Policy Area and Scientific Coordinator of the Pharmaceutical Observatory at Cergas, “France in 2021 has implemented a reform of the Early Access programs that envisages a rational approach as well as an ad hoc fund for Early Access with stringent selection criteria, financial impact assessments with payback funds from the industry if these ceilings are exceeded”. In this vein, our results attest to the funding's central role in configuring french Early Access programs. Indeed, France is the only country to provide an ad hoc fund for Early Access programmes. The costs of drugs provided through EAPs are financed by health insurance. Additionally, central is the level of innovativeness of the drug. The boundaries within which a drug can be considered innovative are more accurately delineated. This is referred to as the presumption of innovativeness, according to which an innovative drug: represents a new treatment modality for the disease, brings a “substantial change” to patients, has an adequate development plan and presents clinical results that support the presumption of a benefit to the patient, there are no significant 'unknowns' related to safety or other vital data.

Early access in the UK

Our analysis highlights that the UK's Early Access to Medicines Scheme is an example of collaboration between healthcare agencies and industry. The government has granted positive Scientific Opinions in several therapeutical areas. Table 4 illustrates the main characteristics of the program. As affirmed in a public declaration by the Chief Executive of the British Liver Trust, “Many patients with liver cancer and liver disease are often diagnosed at an advanced stage when there are limited treatment options. Sometimes, new innovative treatments take a long time to go through the regulatory processes. This Early Access scheme is essential for patients and has the potential to save lives. It means that patients can potentially receive medicines that are deemed safe much more quickly whilst further evidence is collected”. In this vein, as detailed in a public declaration by the Chief Executive of the MHRA, “This is a ground-breaking move, demonstrating our commitment to ensuring that patients can have fast access to promising new treatments ahead of normal licensing timeframes. This life-changing scheme, which has remained running throughout the pandemic, gives patients with life-threatening or seriously debilitating conditions access to medicines that do not yet have a marketing authorisation when there is a clear unmet medical need”.

Table 4 Early Access programs in the UK
Full size table

Our results attested to the authority's role in configuring English Early Access programs. Indeed, there is a two-step process for innovative drugs in the UK: (1) promising designation of innovative medicine (PIM) and (2) Early Access to medicines scientific opinion. A product may be eligible for EAMS based on early clinical results if it has the PIM designation. The PIM designation may be provided many years before the product's authorisation and will be given following a scientific meeting of the MHRA. The analysis of the UK’s Early Access program emerges the relevance of patients’ opinions. The scientific opinion discusses innovative drugs based on information gathered from patients who will benefit from the therapy. The recommendation helps the prescribing doctor and the patient decide whether to take the medication before it is granted a license. In this case, the costs are entirely borne by the industry, and no stringent criteria of innovativeness are made explicit.

Discussion

Based on three characterising dimensions we identify the main factors based on which configuring the Early Access Programs: (1) authorities involved: it refers to the level of engagement of authorities in the entry of innovation in the market (high, medium and low); (2) eligibility criteria: it refers to how stringent the criteria of eligibility of innovative drugs are (high, medium, low) and (3) applicants’ heterogeneity: it refers to the number of applicant targets (high, medium, low). They were identified by analysing the main differences and similarities of each Early Access program among countries. Based on these factors, it was possible to construct a three-dimensional matrix through which institutional actors can identify the strategy to push innovations to the market in a highly regulated context (Fig. 1). Mainly, combining different levels (high, medium and low) of each factor allows us to categorise National programs into three kinds of Early Access programs: (1) Applicant-based programs, (2) Fund-based programs and (3) Authority-based programs.

Fig. 1
figure 1

Different configurations of Early Access programs. Source(s): Authors’ research

Full size image

This paper demonstrates stakeholders’ relevance in a highly regulated context affecting market access decisions (Mukundhan & Nandakumar, 2016; Yu & Li, 2020) confirming some studies (Carayannis et al., 2018; Garousi Mokhtarzadeh et al., 2020; Najafi-Tavani et al., 2018; Wang & Hu, 2020) that have emphasized that innovation increasingly arises from the network level. In the pharmaceutical sector, there is a heterogenous pool of actors including: (1) Patient associations, (2) Universities, (3) Institutes for Treatment and Research, (4) Scientific societies, (5) Health companies and (6) physicians. Each one could be interested in the Early Access of innovation in the market requiring the activation of these programs. Institutional actors are under the pressure of different stakeholders characterised by different interests. Apolone et al. (2019) attested that delayed access to innovative drugs into the markets negatively affects: (1) the requirement for patients to have prompt availability of cutting-edge medications, (2) the demand from healthcare professionals for fresh therapeutic choices for diseases where effective alternatives are lacking and (3) the necessity for pharmaceutical companies to function within a market characterised by transparent regulations. In addition to pharmaceutical companies being interested in expediting the entry of their products into the market, patients and physicians have a strong interest in the activation of Early Access programs. As discussed in detail in previous sections, these programs enable specific patient groups to gain access to medicines for diseases with no alternative therapies available (Costa & Magrini, 2022; Jommi et al., 2021). Consequently, patients’ life expectancy can be prolonged. Patient associations, therefore, form an additional stakeholder group whose influence affects the decisions of institutional actors. Furthermore, the collaboration between the pharmaceutical industry and international regulatory agencies has facilitated the advancement and implementation of various initiatives. For instance, accelerated research and development (R&D) models like the PRIority MEdicine scheme have been established. The primary aim of this scheme is to provide support and optimize the development of medicines. Its purpose is to ensure that patients suffering from untreatable diseases or those in need of better treatment options gain access to new drugs that can improve their overall well-being (EMA, 2018). Consequently, Universities, Institutes for Treatment and Research and Scientific societies advocate for the development of collaborative approaches among institutional actors. These collaborations aim to foster innovation and enhance the efficiency of the development process, particularly in therapeutic areas with significant unmet medical needs. Furthermore, our analysis extends the literature attesting that the level of actors’ heterogeneity (high, medium, and low) influences entry strategy configuration. Indeed, the literature on stakeholder theory highlights the central role of external heterogeneous actors (Bonnafous-Boucher & Rendtorff, 2016; Hörisch et al., 2020; Lee & Raschke, 2020). Recent studies have recognized the relevance of stakeholders’ heterogeneity (Bettinazzi & Zollo, 2017; Jakhar et al., 2019; Santoro et al., 2020). Differences in values, role expectations, incentive structures, objectives, languages, understandings, cultures, and practices influence actors' heterogeneity (Mukundhan & Nandakumar, 2016). Other authors have highlighted heterogeneity as having detrimental impacts and impeding the functioning of individuals, organizations, and businesses (Bettinazzi & Zollo, 2017; Ding et al., 2016; Schneider & Sachs, 2017). However, heterogeneity also fosters creativity and enhances group interaction (McGahan, 2021; Santoro et al., 2020). For instance, in Italy, the large number of applicants for Early Access programs reflects the heterogeneity of stakeholders.

Our paper extends the literature showing the relevance of eligibility criteria as an influencing factor in Early Access programs configuration. In Italy, there are very stringent requirements for innovativeness. In France and the UK, the level of eligibility criteria drops. Indeed, the authorities in these countries set criteria of “presumption of innovativeness” and “promise of innovativeness”, respectively. This leads to an increase in granted Early Access programs and the number of patients benefiting. Indeed, a firm’s competitiveness depends on product innovativeness (Hashai & Markovich, 2017). The innovation quality released to the market determines the value a company’s innovation will provide (Mariani & Wamba, 2020). The product quality phenomenon considers two essential elements: consumers’ willingness to pay, influenced by how innovative the product is, and the potency of the available intellectual property rights protection (Berger, 2019).

Additionally, this paper confirms authority’s engagement (high, medium and low) as one of the main factors influencing market entry programs. To gain a competitive position within a new market, firms attempt to alter their behaviour to conform to that of previously extant market organisations and to follow the standards imposed (Parente et al., 2019). Firms find it challenging to understand the institutional structure since they must follow the standards imposed by different actors (Parente et al., 2019). These requirements considerably affect producers’ income and market access (Mohan, 2020). The role of institutional authorities in highly regulated contexts is central (Jin et al., 2019; Hashmi & Alam, 2019). By supporting fundamental public research, the National Institutes of Health play a significant role in fostering market access for innovative drugs (Aldieri et al., 2020). The institutional framework influences many organisational elements, including market entrance plans (Markman et al., 2019).

Drawing these assumptions, our findings emphasise that the intersection of different levels (high, medium and low) of authority’s engagement, eligibility criteria and applicants’ heterogeneity, determines the configuration of different Early Access programs.

Particularly, the applicant-based programs originate from a combination of a high level of applicants’ heterogeneity and eligibility criteria and a medium level of authority’s engagement. For instance, several stakeholders acting as applicants in Italy implies activating various Early Access programs. This may be one of the reasons why Italy has shorter access times to the reimbursement list than most European countries. On the other hand, the high degree of fragmentation and uncertainty characterising the Italian Early Access system may limit innovation (Blind, 2016). On the contrary, the applicants’ heterogeneity in France and the UK is lower. Only manufacturers and physicians can apply for Early Access programs in these countries. This results in the definition of few Early Access tools and, simultaneously, in low fragmentation and uncertainty.

Secondly, the authority-based programs originate from a combination of a high level of authority’s engagement and a low level of applicants’ heterogeneity and eligibility criteria. For instance, in the UK, manufacturers and physicians applying for Early Access programs undergo a two-stage approval process. Additionally, every three months, the program is re-evaluated. This increases the product validity placed on the market and, consequently, patient benefits. The fund-based programs originate from a combination of medium level of each factor. Central here is the role of financial support from institutions to stimulate the activation of Early Access programs. For instance, France is the only nation to offer an ad hoc fund for Early Access programs. Neither the pharmaceutical industry nor the patients are charged for the coverage of the drugs by health insurance. Thus, France is defined as a “pioneer” of Early Access programs. It has many granted Early Access programs and patients who benefit from it.

Conclusion, implications and limitations

In conclusion, this research offers an inductive conceptual model to identify the main factors pushing innovation to access highly regulated markets. The results highlight the need for institutional actors to strike the right balance between several factors. The comparative analysis shows that the perfect combination of applicants’ heterogeneity, authority's engagement and eligibility criteria allows for reduced time of innovation entry. In this vein, France is the best example of the right mix. Our study provides valuable insights to overcome principal barriers to entry of innovation in the market, focusing on external factors. This research offers valuable insights for academics, managers and policymakers. This study distinguishes itself from existing literature by not solely considering compliance with the regulatory framework as the sole determinant of legitimacy and market survival. Instead, it analyzes regulatory pressure in a negative light, perceiving it as a hindrance to innovation. By doing so, the research offers scholars a fresh perspective through which they can analyze the introduction of innovations into markets that are characterized by significant institutional and regulatory pressure. The inductive conceptual framework expands upon the current literature by theorizing various entry strategies and identifying new primary and interconnected dimensions.

This analysis highlights for policymakers the need to strike the right balance between innovation and regulation by dosing correctly the heterogeneity of the actors involved. It would be desirable to develop a culture and sensitivity to innovation within the regulatory development bodies by defining policies that encourage the development of innovative ideas. Adopting tools such as Early Access would enable institutional decision-makers to reduce barriers to entry for innovations in highly regulated markets. In fact, it overcomes some major obstacles. It reduces the number of actors that companies must interface with to promote their products and provides more certainty about the timing of adoption decisions. Furthermore, it would be advisable to provide pre-established mechanisms through which to monitor the impact of innovation on the entire value chain. Furthermore, to keep up with the constantly evolving innovation process, it is necessary to establish periodic review mechanisms for innovation regulations.

The analysis also offers food for thought managers of pharmaceutical companies who should focus on identifying the best country in which to activate Early Access Programs based on the level of regulatory pressure. Although our findings have shed light on several key issues, this research is not without limitations. Measuring with a longitudinal approach could be interesting to understand better the effect on innovation that a change in high regulation could have. The study would gain validity if it continued over time, thus adopting a longitudinal rather than a cross-sectional perspective. The pharmaceutical is one of the most innovative sectors. It needs to create value and scientific advances. This framework allows for the protection and guarantee of quality in the pharmaceutical industry.