Abstract
1. Introduction
With the growth of cooperative forms of management, positive perspectives on cooperation have, over the last decade, enjoyed a notable revival, especially when compared to the dominant strength of the competitive model as a paradigm of resource allocation efficiency [1]. The high level of competition in the business environment pushes firms towards new learning models based on the high value of relationship patterns: firms interact to successfully learn from one another [2]. Moreover, innovation is increasingly recognized as requiring the convergence of many sources of knowledge and skills, usually linked through a network [3].
Therefore, since the late 1980s, the rate of interorganizational alliances, or voluntary agreements between firms involving the exchange, sharing, or codevelopment of products, technologies, or services, has accelerated in multiple industries [4].
This situation is particularly true in an R&D intensive sector such as the pharmaceutical industry, where innovation is perhaps the most relevant performance driver. The pharmaceutical industry is characterized by the growing phenomenon of alliances and mergers and acquisitions (M&A)—both of which are strategic paths to increased reliance on external sources in a vertical de-integration process—due to some remarkable tendencies. These are mainly connected to R&D activities and reflected in increased regulatory constraints and technological complexity.
Some authors have suggested that the industry is facing a crisis that threatens the established model [5] and some tensions in the business model have begun to emerge.
In fact the dynamic and uncertain scenarios that economic organizations have to face force them to deeply rethink themselves and their structure through an internal innovation process aimed at making them more reactive and proactive, often through networks of informal relationships [6].
Several factors are contributing to a crisis in the R&D area, such as the continuous change in the process of drug discovery and development, the cost containment policies of institutions, the increasingly stringent requirements for the approval of new drugs resulting in more costly, long, internationally-based R&D activities [7], the growing number of patent expirations on blockbuster drugs, the enhanced competition from generic drugs, the growing importance of emergent countries [5], and an increase in the percentage of failures or non-completions in the R&D process.
At the same time, the crisis in the productivity of pharmaceutical R&D organizations, as opposed to the positive results produced by biotechnology R&D, is leading to the development of bio-pharmaceutical firms [8], in which biotechnological opportunities are integrated with pharmaceutical ones.
All these elements are forcing the industry to make adjustments to established patterns: pharmaceutical companies are searching for new, more efficient ways of managing the drug development process, while maintaining the process's ethical integrity through M&A, in-licensing, alliances, new organizational and decisional structures of R&D, and outsourcing that are changing the traditional model of vertical integration of the pharmaceutical industry.
Outsourcing practices, widely applied and boosted by the rush of corporate downsizing as an alternative to divestiture [9], have varied over the years, covering a diverse range of services from support activities to core managerial processes and from service-based activities to productive processes, such as modular production [10]. In knowledge-intensive industries (e.g., pharmaceutics, biochemistry, and healthcare), selective outsourcing usually occurs in favour of specialized and focused suppliers [11]. In fact, contract research organizations have become a fundamental component of R&D.
In the end, a pharmaceutical firm cannot exist without networking in the scientific community: the amount of resources and knowledge needed for R&D has become overwhelming for a single organization; technological and market uncertainties foster the search for new opportunities; and performing R&D activities in networks can produce extra value for the participants and for innovation outcomes [12]. From an organizational point of view, not only the managerial components of R&D but also patent, regulatory, and commercial aspects are involved in all stages of R&D [8].
2. Research Problem
Starting from these premises, the aim of the paper is to investigate a specific form of alliance, the
The work tries to enrich the line of inquiry into cluster-based innovation by studying the effects of networks on clinical research.
Clusters are localized networks [13], territorial aggregations of different players, that usually arise when business segments require high levels of specialization from multiple contributors [14]. They can have a more or less formalized structure, and, in any case, they assume a network configuration through contractual mechanisms.
The cluster we analyse involves a public, an industrial and an academic player, which, in the pharmaceutical industry, typically comprise pharmaceutical firms, biotech firms, universities, research centres, and healthcare organizations such as hospitals, clinics, and healthcare institutions.
As for the relevance of the topic, it is grounded in reality because the
(2) Interactions between complementary players are needed for innovation. Firms must deal with the new systemic dimensions of technology and research. The strength of the cluster in the pharmaceutical industry can be said to rest upon the fact that research is built on three pillars: basic academic research, corporate R&D, and clinical R&D. Diverse actors contribute together to these three crucial elements.
Since pharmaceutical clusters are composed of players who have different roles in the value chain, operating in a pharmaceutical R&D process, we can presume that it is very likely that each player in the cluster has ties with similar organizations (with the same role in the value chain) that are however involved in other clusters. This assumption has driven us to the
As for the literature on clusters, we can analyse simultaneously
As for the literature on networks, we contribute to the debate on the network structure most beneficial for innovation. A
The paper examines the impact of
Finally we go further and enrich the
The research questions are the following:
3. Literature review
3.1 Networks
Studies that examine the consequences of networks 2 typically follow the structuralist perspective. This line of inquiry focuses on the configuration of ties, analysing how actors in networks influence each other's attitudes and behaviours, and concluding that an actor's payoff is a function of the network structure and of its position in the network. The literature suggests that a firm's network of relationships influences its rate of innovation and R&D [16–18], often highlighting the benefits of networking. Networks allow knowledge sharing (knowledge, skills, physical assets) and knowledge flows (information conduits about technical breakthroughs and new insights) [16]. The greater the social capital possessed by the firm, the greater its knowledge will be, and therefore, the faster its innovation process [19].
Scholars supported competing schools of thoughts and two trade-offs are still in place: the first one is between the benefits of strong [20–21] versus weak [22] ties (that are likely to be bridges), the second one is between the benefits of disconnected network structures [23] versus dense network structures [24–25]. The question is whether network positions associated with the highest economic return lie between or within dense regions of relationships. Despite the considerable focus on the role of network structures in explaining firm performance outcomes, some researchers have acknowledged that a network of ties merely gives the focal firm the potential to access the resources of its contacts [26]. Contingencies need to be introduced, such as nodal heterogeneity [27].
3.2 Clusters and small world networks
The concept of a network is more general than that of a cluster and does not necessarily entail local embedding, a shared objective, or a specific market [28]. The cluster concept has been defined in ambiguous ways. The full range of cluster definitions falls under two main lines of conception: (a) definition in reference [29]: “a geographically proximate group of inter-connected companies and associated institutions in a particular field, linked by commonalities and complementarities”, (b) definition in reference [30]: “networks of production of strongly interdependent firms, knowledge producing agents (universities, research institutes, engineering companies), bridging institutions (brokers, consultants) and customers, linked to each other in a value-adding production chain”, a mainly reticular conception of clusters. Contrary to the definition in reference [29], the approach of reference [30] is not very explicit on the issue of proximity, and it stresses the frequently localized but open nature of clusters: “in most cases they operate within localized geographical areas and interact within larger innovation systems at the regional, national and international level”. In the end there is no clarity on the geographical as well as on the sectoral characterization of clusters.
A cluster - an aggregation of different players in a localized network [13] - has been better characterized by reference [31] in this way:
In particular, we consider the impact of
The
This reconciles the local properties of a regular network with the global properties of a random one, by introducing a certain amount of random long-range connections into an initially regular network [33], therefore the edges of the network are divided into “local” and “long-range” contacts. The authors argued that such a model captures two crucial parameters of social networks: there is a simple underlying structure that explains the presence of most edges, but a few edges are produced by a random process that does not respect this structure.
This is useful in reconciling competing views in the literature on networks: the benefits of strong vs weak ties and of disconnected [23] vs dense [24] structures.
The main characteristics of
Since we are interested in the impact of
Reference [35] showed that innovative research in biomedicine has its origins in regional clusters in the United States and in European nations. The success factors of a cluster have been identified with reference to the life-science industry as (a) proximity between university and research institutes and industry, with cross-fertilization and know-how sharing; (b) access to human capital; (c) availability of infrastructures such as facilities and transportation; (d) cultural openness; (e) multidisciplinarity and spillovers, with interactions and synergies among disciplines; (f) development of fiscal and financial conditions supporting innovation.
Clusters reflect the systemic character of modern interactive innovation, and therefore they are related to several conceptual frameworks and models developed under the literature on innovation systems. In this field, which emphasizes interactions among actors and innovation as a process embedded in a given social context, research has been carried out on sectoral systems [36], technology systems [37] and regional systems. The frameworks “mode 1, 2 and 3” of knowledge production trace the evolution from the linear model of innovation to the interactive, non-linear model. We refer to “mode 3” of knowledge production, which advocates a system, consisting of innovation networks and knowledge clusters for knowledge creation, diffusion, and use [38]. This is a multilayered, multimodal, multinodal, and multilateral system, encompassing and reinforcing mutually complementary innovation networks and knowledge clusters characterized by the coexistence, coevolution, and cospecialization of different knowledge paradigms and different modes of knowledge production.
This recall also the “Triple Helix” (TH) model of knowledge, developed by references [35–36], focused on three helices that intertwine and thus generate a national innovation system: academia/universities, industry, and state/government. References [39–40] spoke of “university-industry-government relations” and networks, also placing a particular emphasis on “tri-lateral networks” where those helices overlap and create synergies that result in product and process innovations. Strong, enterprise-supporting infrastructures complement strong, local science bases [41] challenging the conventional, linear model of interaction. Universities provide advanced research and a ready supply of human capital in the form of skilled graduates and basic research; companies provide real-world problems, commercialization opportunities, and funding. Innovative dedicated biotechnology firms (DBFs) seek to commercialize the results of the basic research; large pharmaceuticals provide funding, downstream marketing and distribution capabilities [42]); and governmental organizations provide user feedback and regulatory support.
Many studies analysed the role of university–industry relationships in triggering new industrial R&D innovative projects [43] and found a positive impact [44–45].
4. Hypotheses development
The aim of this paper is to study the concepts used to characterize the
4.1 Small world network structure
We refer to the
We can deconstruct the
A dense innovative cluster provides benefits both from the learning and the governance perspective, favouring the
From the learning perspective, it facilitates the local transmission of information by providing numerous communication channels and pathways among actors, so that information introduced into a cluster will quickly reach other actors in it; it assures the future existence and relevance of different multiple sources of information; allows triangulation (i.e., by utilizing third parties to aid the judgment of knowledge and its absorption) [16,24]; facilitates intense interactions and knowledge integration [47]; improves the transfer of tacit, embedded knowledge [48–49]; enhances interfirm cooperation [47]; favours mutual understanding based on common norms or behaviours; increases the potential to build knowledge through intensive, repeated interactions and the exchange of ideas; and allows coordinated action.
From a governance (TCE) perspective, it reduces transaction costs, allowing easier interactions between partners; reduces barriers to resource mobilization; reduces competitive practices; discourages misbehaviour, due to the so-called “shadow of the others” and “shadow of the future”; fosters a normative environment against opportunism; reduces risks; and engenders mutual trust, reciprocity norms, and shared identity, thus facilitating collaborative efforts by making the actors more willing to exchange information [16, 50].
On the other hand, the presence of structural holes allows the detection and the development of new ideas from remote parts of the network synthesized across disconnected pools of information, new opportunities, diverse experiences, and new understandings; the preservation of variety and heterogeneity, through the access to resources that are different from those found in an actor's more immediate social network [22]; interfirm resource pooling [47]; flexibility; arbitrage opportunities for the brokering actors [51–53]; and novel combinations and re-combinations of ideas. These conditions favour the
In the end, while the presence of structural holes is suited to idea generation and invention, as it favours exploration and hampers implementation/action, a dense network structure is suited for idea implementation (coordinated action to implement ideas), as it favours exploitation but could potentially have an idea problem.
The application of this debate to the pharmaceutical context and to the clusters can result in the following arguments.
Some arguments suggest that
In fact, density is especially useful in the pharmaceutical industry because the innovation process, which is a complex sequence of stages, is a trial-and-error process, with a lot of feedback loops and continuous shifts from exploration to exploitation as well as the opposite, which requires interaction.
We could argue that in the specific context of the pharmaceutical industry, inside a single cluster the processes of
Therefore, inside a pharmaceutical cluster, in the cluster there is a finalized and structured exploration, a concept that is more similar to exploitation for certain characteristics, and for this reason the dense structure seems to accomplish both
Since we have varied players both inside and outside the clusters and usually exploration comes from variety, we have considered innovation as comprising
Due to different formation conditions and causes, clusters typically own heterogeneous knowledge that can migrate and be fruitfully recombined through links that span those clusters.
Therefore, the presence of structural holes spanning between a cluster and other clusters (a configuration based on semi-isolated subgroups) determines the extent to which the cluster's knowledge base is continuously rejuvenated through knowledge inputs from outside the cluster [56] and novel combinations of ideas.
While authors studying
Therefore, we are considering an open cluster, where some members are engaged in relations with organizations belonging to other clusters, playing the role of the bridge [58]. This is a solution that tries to also join the conceptions of clusters of reference [29] and of reference [30], as explained in the literature review.
Combining the organizational learning arguments with the small-world networks concept, we conclude that networks that have both clustering and some amount of linking between them, cluster-spanning bridges, spur each cluster innovation, striking the balance of
The bridging ties with other clusters allow for outside exploration through the possibility for any point in the network to benefit indirectly from the information or the knowledge received by his neighbour in other clusters [57], with the access to heterogeneous and novel ideas, while the high density of clusters allows for effective exploitation of ideas and inside cluster exploration. The benefits of local transmission and the information scope of cross-cluster connections can be simultaneously achieved.
Dense and sparse configurations coexist at different scales and levels of the network, in a multiscaled cluster. Density comes from intra-cluster dynamics, while sparseness comes from inter-cluster dynamics, to assure the cluster life in the short as well as in the long term with the capability of catching new ideas from outside and of effectively implementing them inside the cluster in wider innovation oriented networks.
Closure allows us to realize the value buried in a structural hole, effectively implementing the new ideas obtained from outside inside the cluster [59].
This means that
Therefore, in sum, we can formulate the following hypothesis:
4.2 Contingencies
Although the solution of combining density in the intra-cluster dimension and brokerage in the inter-cluster dimension is undoubtedly conceptually attractive, it appears likely that its impact on innovation will be contingent on several elements. We focus on two relative properties of the nodes as contingencies: partner heterogeneity and geography.
4.2.1 Heterogeneity
Pharmaceutical clusters comprise different actors, which occupy different positions in the supply value chain, from downstream to upstream: pharmaceutical, biotech firms, universities, research institutes, institutions. From the “Triple Helix” Model of knowledge [39–40], we know that when three helices (universities, industry, and government) intertwine, through relations and networks, they overlap and create synergies that result in product and process innovations. Universities provide advanced research and human capital; companies, real-world problems, commercialization opportunities; institutions, user feedback and regulatory support.
This system provides a broader view of the value chain and interaction between private and public actors in innovative R&D activities [60].
However, diversity can represent both an opportunity (novelty value), favouring knowledge development, and a problem (reduced absorptive capacity, higher transaction costs), disfavouring knowledge transfer [28].
The impact of heterogeneity on innovation appears different in the local (intra-cluster) and long-range (inter-cluster) setting of the
On one side, in the
Reference [62] argued that it is the
Moreover, vertical diversity allows the effectiveness of the
Considering the context of the pharmaceutical industry, we can point out some additional remarks. First, partner diversity is really important to answering the regulatory requirements. The life-science R&D process is scheduled as a strict sequence of different stages that will be better performed if they involve different specialized players, covering different roles and responsibilities. Moreover, diversity will better allow feedback loops and support a trial-and-error sequence, typical of life-science industry R&D [63]. Second, vertical diversity in this industry means also complementarity. Therefore, a cluster high in vertical diversity implies that firms may specialize in either exploitation or exploration, and seek the other through relations with other organizations with complementary specialization. Furthermore, in the literature, arguments have been made that when firms combine complementary skills, greater innovation results [64]. If partners' vertical diversity implies complementarity, which in turn implies innovation, partners' vertical diversity drives innovation.
Therefore,
On the other side, in the
It is true that partner diversity in the pharmaceutical industry involves a related knowledge background: players act in subsequent phases of the same macro-process, and thus it is possible to suppose that they have the same background in terms of basic skills, shared language, and knowledge of the most recent scientific or technological developments; techno-organizational systems (TOS), molecules, and drugs [65]. This reduces the concern of an absence of absorptive capacity.
However, in any case, if learning performance from interaction is the mathematical product of novelty value and understandability, the result is an inverted-U shaped relation with cognitive distance. Optimal cognitive distance lies at the maximum of the curve where there is a sustainable level of transaction costs and competition, and a good level of complementarity and absorptive capacity.
Therefore,
A moderate level of vertical diversity between the two nodes spanning the inter-cluster structural hole enhances the positive impact of the inter-cluster structural hole on the cluster's innovative performance; while a level that is too low or too high reduces this impact.
Finally, we can state the following hypothesis:
4.2.2 Geography
In the literature some elements support localization and proximity for innovation, others a wider geographical extension.
Factors supporting geographical proximity are: transaction costs reduction and development of relational dimensions; location-specific drug development for epidemiological reasons; location-specific regulatory framework; tacit knowledge transfer, frequency of interaction, trust; location-specific assets (agglomeration economies, pool of skilled labour; scientific, commercial spillovers) in positive
Clusters of which all individual elements are to be found in a confined area are the exception rather than the rule. Especially in some industries, it might even be counterintuitive to expect “complete” clusters at the regional or national level, as the relevant knowledge base is strongly dispersed, as in the pharmaceutical industry.
For instance, drug companies are beginning to invest in Chinese R&D; in fact, the Chinese market may become the second-biggest pharmaceuticals market in the world by 2020. Recent studies show that the famous Italian industrial districts are facing a crisis [67]. In order to survive they are becoming locally disembedded, shifting some activities, especially in production, outside the local environment [68].
Therefore, a better solution for innovation would be a balance between local and non-local players in the
Therefore, we can presume that
This means that a moderate level of geographic distance between the nodes in the life-science cluster enhances the positive impact of density; while a level that is too low or too high reduces this impact. Similarly, a moderate level of geographic distance between two nodes spanning an inter-cluster structural hole enhances the positive impact of the inter-cluster structural hole on the cluster's innovative performance; while a level that is too low or too high reduces this impact.
Finally, we can state the following hypothesis:
5. Analysis
5.1 Sample and data collection
We explored the arguments mentioned in the previous sections by using a social network approach and a regression model applied to the U.S. pharmaceutical industry.
We built a sample including eight pharmaceutical clusters in the U.S. and their firms, which are industrial, academic and institutional organizations.
To obtain the final sample, the following procedure was followed. First, a list of all the pharmaceutical clusters established in the U.S. was drawn up using the
We retrieved the list of clusters for four years: 2007, 2008, 2009, 2010. Second, we identified the nodes composing each cluster (firms, institutions etc.) through complementary sources:
The minimum number of nodes in the clusters is 92, the maximum 645. The final sample includes the following eight clusters (CL): CL1: Life Science Alley; CL2: Massachusetts Biotechnology Council; CL3: Oregon Bioscience Association, CL4: BIOCOM; CL5: Arizona Bioindustry Association; CL6: Nashville Health Care Council; CL7: North Carolina Biotechnology Center; CL8: Connecticut United for Research Excellence, Inc. The number of nodes composing each cluster is respectively: 645 in CL1, 590 in CL2, 167 in CL3, 546 in CL4, 232 in CL5, 257 in CL6, 595 in CL7, 92 in CL8.
In order to build our dependent variable, we collected patent data for each cluster from the
As for the attributes, we considered: a) the nodal characteristics: for each node in the clusters we identified the type of organization, i.e., the role in the vertical chain, and the geographical location. We obtained different categories for the firm type (e.g., biotechnology, pharmaceutical, academic institution etc.) and the states in which the firms are located. We used the sources mentioned above; b) the cluster's characteristics: the number of employees and the cluster's specialization (from U.S. Cluster Mapping Database).
As for the relational data, we collected all the transactions and agreements between the nodes of the cluster related to research and development, and distinguished short-range intra-cluster from long-range inter-cluster ties.
To retrieve these data we combined the sources mentioned before with the
In figure 1, the long-range, inter-cluster ties are summarized: each of the eight clusters is connected to external clusters through the linkages of its nodes to other clusters' nodes; the thickness of the segment represents the strength of the connection as a function of the number of ties.

Long-range, inter-cluster ties
In this way we reconstructed both the whole network and the single sub-units of the network, which are clusters.
Finally, we adopted a
5.2 The model
Traditional estimations of the effects that network variables have on the innovation of a cluster are carried out with a regression model. The regression equation can be written as follows, using a pooled cross-sectional notation 9 :
where C: Cluster's, N: nodes', SH: structural holes.
We used a time-lag of one year between the dependent variable and the regressor values: the dependent variable is computed at time t, while all the regressors are computed at time t−1.
The dependent variable, cluster's innovation performance measured through the number of patents, is a variable that takes only non-negative integer values. Since the assumption of the linear regression model of homoskedastic normally distributed errors is violated, a count model should be used. Poisson regression is the standard or base count response regression model [72]. We considered six statistical specifications, following reference [73] who explained panel models for counting data, mentioning four panel Poisson estimators - pooled Poisson with cluster-robust errors, population-averaged Poisson, Poisson random effects (RE), and fixed effects (FE) and Negative binomial models RE and FE. We finally choose
5.3 Variables and measures
The
The
The
5.4 Results
The regression was implemented on eight clusters, with 32 observations over the four years analysed.
As Table 1 shows, the results support the hypotheses, and the mechanisms referring to the impact of
p<0,05
p<0,01
p<0,001.
Standard errors are in parenthesis
Hypothesis 1 investigated the impact of the
The effect of each of the components taken individually is the same as the effect of the interaction term. As for the short-range intra-cluster ties, the cluster density is associated with the superior cluster's innovative output. In fact, the resulting coefficient of the variable
As for the long-range, inter-cluster setting the inter-cluster spanning of structural holes is associated to a greater cluster's innovative output. In fact the resulting coefficient of the variable
Two moderation effects, related to nodal characteristics, were predicted as being likely to intervene in this process, introducing a contingent approach in the
The first effect involves nodes' vertical heterogeneity and corresponds to Hypothesis 2.
Hypothesis 2 predicted two effects.
First, that the
Second, it predicted that the
The second moderation effect involves nodes' geographical distance and corresponds to Hypothesis 3.
Hypothesis 3 predicted two effects.
First, that the
Second, it was hypothesized that the
As for the control variables in the full model,
6. Discussion and conclusions
The main contribution and results of the study are a framework that suggests an understanding of the factors that give rise to differential innovative outcomes across different clusters, by using a network approach. In particular we tried to hypothesize the impact of a cluster's
By using the concept of
However, one limitation of the study is the low level of
Finally, the work could be further improved from an empirical point of view by enriching the model with more control variables, like the financials of the nodes composing the clusters (e.g., ROA, current ratio, debt to equity etc.).
The results provide a test of the impact of a
A form of organized economic activity that involves a set of nodes (e.g. individuals or organizations) linked by a set of relationships.
Actual number of direct ties between nodes as a ratio of the maximum possible number of ties.
A structural hole exists between the brokered actors, two nodes in a network, if the nodes share a tie with an individual but are not connected to each other [23]. Bridges between groups of nodes span structural holes with weak ties.
The whole firm could be studied as a smallworld network and the workgroups could be considered as clusters interacting with one another [57].
Vertical diversity can be defined as the cognitive distance and differences in alliance partners' operational contexts in the value chain, it implies a distinction among three categories: horizontal, upstream, or downstream [61]. For instance a biotech and a pharmaceutical firm are diverse, two pharmaceutical firms are equal. Vertical diversity in
The ability to recognize, assimilate, and apply external knowledge.
From Harvard Business School, a project funded by the U.S. Department of Commerce, Economic Development Administration.
We use a longitudinal research design and therefore all the variables are indexed over firms (i) and over time (t).
