The value of collaborative research in rare disease research

KEYWORDS:

• Collaborative science
• rare disease
• research consortia
• data sharing

Successful collaboration in research is being recognized as the next hurdle to overcome in advancing medical science. Recently, Vice President Joseph Biden was reportedly astonished by the lack of existing collaborative infrastructure in the current research environment.[1] While significant scientific breakthroughs – such as revolutionary advances in genetics – can transform some aspects of medical research, a more difficult aspect to change is based in culture. Historically, the competitive nature of scientific research served to spur innovation and was intended to speed advancements, yet these same characteristics disguised a serious flaw in this system. Collaborative research is an exercise in trust to the degree that significant data sharing is required at all levels of investigation. Yet enhanced innovation, a supposed benefit of competition, is negated by an historical resistance to collaborate authentically in the face of competition. So deeply entrenched is competition in basic and clinical medical research that scientific careers can be made or broken based on ‘winning’ the next grant, the next patent, or professional attribution for the next big innovation.

University-based research is also beholden to the competitive model for its bearing on institutional reputation and ability to attract and keep top flight researchers. Indeed, academic medicine as a whole seems reluctant to share data with the larger community, even after studies are complete and data are analyzed.[2] Private industry naturally guards research data closely, as these data can potentially result in development of a lucrative product. In this historically competitive environment, typically the only way competition is overcome and collaboration can get a foothold is when a large federal agency steps in to broker partnerships through influencing the policies around funding, publication, and data sharing. Examples of initiatives that push forward collective research in the U.S. include the Global Rare Diseases Registry Repository, sponsored by the National Center for Advancing Translational Science. Registry databases and tissue repositories are essential tools for providing important common data elements to a broad community of researchers. Similar examples in the global rare disease space include the International Rare Disease Research Consortium and ERA-Net for Research Programmes on Rare Diseases, which function at the funding level to connect disparate institutions with similar interests and leverage resources to group data. Data and data platforms, repositories, and registries are all essential tools in the effort to effectively engage in the collective research approach necessary to make advances in rare disease research.

Collaborative research, as opposed to collective research, is equally necessary and entails an ability to conduct concurrent trials at multiple sites. U.S.-based researchers, intent on making scientific headway, express frustration over the way in which our scientific and medical research systems and policies function in comparison to their European counterparts. Different priorities regarding health data and personal privacy laws in other countries allow for freer sharing of data, resulting in larger data sets and potentially more rapid advances.

Thoughtful and well-designed collaborative research is essential to producing not only strategy, but operational framework in which collaboration can become truly productive. Moving research collaboration from the conceptual stage to a fully functional entity can be daunting. While most, if not all, researchers enjoy the intellectual stimulation of exchanging ideas with equally committed colleagues, introducing operational complexity into the collaborative process can hinder cooperation.[3] The time and energy necessary to negotiate contracts among various institutions to allow for authentically free-flowing information, can stand as a barrier to even the most committed researchers.

Fortunately, the tides are beginning to turn towards a more favorable view of collaboration among leading researchers and institutions, spurred on in part by governmental initiatives that recognize how essential multiple resources are to solve large and complex problems. The need for collaboration is especially evident in rare disease research, where numbers of patients are so small as to stymie construction of adequately powered trials in the absence of multiple sources of data. Data sharing, as it occurs in collaborative research, is critical to producing meaningful results in rare disease research.

While there is depth to the literature in science and technology studies that support collaboration as a positive mediator of productivity, the concept remains difficult to define and measure.[4] Outcomes from collaborative research produce more ‘bang for the buck’, if you will. Using citations and the impact factor of peer-reviewed literature as a metric, international collaborative research is more widely read and considered more relevant than domestic and single authored papers.[5,6]

While co-authorship has been a traditional metric of collaboration, measuring authentically collaborative research where members contribute knowledge, data and labor is much like measuring the proportional contributions of cake ingredients from the batter in the bowl. Collaboration encompasses multiple activities, some overt and negotiated, such as division of labor, and some that remain understated like knowledge transfer and mutual inspiration.[7]

In her comprehensive discussion of scientific collaboration, author Sonnewald (p. 647) notes that ‘Scientific collaboration occurs within the larger social context of science, which includes elements such as peer review, reward systems, invisible colleges, scientific paradigms and national and international science policies, as well as disciplinary and university norms’ [8]. The significance of this recognition lies in the ways in which culture influences the production of scientific (or medical) knowledge. Culture functions as both barrier and facilitator to collaborative research. For instance, while collegial relationships and professionalism with a research group go a long way towards overcoming competitive incentives, the institutional norms and priorities that operate can moderate a researcher’s ability to garner sufficient resources and participate fully.

Other key elements of research consortia, most frequently embarked upon by scientists whose commitment to solving a problem outweighs individual career advancement, are that collaborative research topics are generally more complex than those initiated by individual researchers.[6] Thus, those scientifically complex issues that require varied resources to adequately address tend also to be the most organizationally complex ventures to produce. Sadly, lack of apparent or sufficient progress is one of the most frequent reasons consortia disband, in the absence of recognition that in comparison to research done individually or institutionally, the level of complexity is more advanced. Sustainability of consortia requires the support of the institutional research administration executives, who can lend resources and support to the team’s members during fluctuations in productivity. An understanding on the part of funders, university research deans, and others is essential to maintaining the consortia when competition for limited resources is intense.

Data sharing is particularly important in rare disease research; small numbers of patients contribute to a moderate pace at best on the road to major breakthroughs. Collaborative research is essential within rare disease research in order to produce scientifically meaningful results and engender confidence in subsequent clinical management of patients.

One example of a rare disease consortium that has risen above all the barriers to succeed is the MDS Clinical Research Consortium,[9] which brought together six of the leading academic research institutions to focus on myelodysplastic syndromes (MDS). Sponsored by the Aplastic Anemia and MDS International Foundation, and funded through the generosity of the Edward P. Evans Foundation, the MDS Clinical Research Consortium just completed its third full year of operation and has garnered the attention of national and international researchers in the field of hematology. Each year of the consortium has brought more clinical trials online, produced increasing numbers of abstracts presented at the American Society for Hematology’s Annual Meeting, and in three short years, the consortium has now begun to contribute to the medical literature on MDS from data generated by this enterprise. The commitment to data sharing and collaborative research among the six institutions has blossomed into partnerships with pharmaceutical innovators, and international colleagues alike. Working together, this consortium has been able to recruit sufficient numbers of patients to power meaningful clinical trials and exchange tissue samples to extend the resources and ability of researchers at the respective member institutions.

Expert opinion

Advantages to collaboration in research greatly outweigh the barriers, and make no mistake – there are significant barriers to engaging normally competitive institutions in cooperative action. As research professionals know, the process of medical research is highly complex even within a single institution. Across institutions the negotiations increase in complexity, as each institution strives to maintain its own standards while engaged in shared research endeavors. Vital procedures designed to evaluate scientific value, protect human subjects, assign shared institutional resources, ensure appropriate legal protections, and maintain credit for achievements must be adhered to, while simultaneously engaging in counterintuitive practices such as sharing preliminary data and intellectual property. As collaborations and formal consortia continue to develop, the system which supports these efforts will need to become more responsive to the needs of researchers. As young investigators attempt to build careers while engaged in collaborative activities that have traditionally been reviewed with skepticism, the reward system in academic and medical research will have to evolve to reflect the new standard.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.