Advancing trial design in progressive multiple sclerosis

The failure of a majority of clinical trials in progressive multiple sclerosis (MS) has highlighted the need to reconsider how these trials are designed and conducted, and many areas deserve focus. Basic scientists are reconceptualising the pathophysiology of progressive MS into three broad areas: systemic inflammation, compartmentalized inflammation and non-inflammatory neurodegeneration, with the latter two becoming predominant as the disease progresses. This framework will guide the choice of experimental therapies. Previous clinical trials have highlighted how participant selection can have a significant impact on study outcome. Phase 2 biomarkers which are biologically stable, dynamically changing over time, and easy to assess in multi-centre studies are greatly needed. Shortcomings inherent in the Expanded Disability Status Scale are prompting the development and validation of better clinical measures. The standard two-arm, fixed-duration trial paradigm has been challenged with new, innovative approaches that can test more therapies efficiently. International collaboratives such as the Progressive MS Alliance will support increased dialogue with regulators, industry and other funding agencies. Better engagement with people living with progressive MS will transform them from simply being the recipient of MS therapies to partners in the search for new treatments. Focused, targeted action will drive further development of effective therapies for progressive MS

The Structural Genomics Consortium: successful organisational technology experiment or new institutional infrastructure for health research?

In a sector characterised by patenting, direct appropriations and returns from investment, the Structural Genomics Consortium (SGC) constitutes a radically different public-private and entirely open access approach to pre-competitive research. This paper discusses the significance of findings from the first independent review of the SGC. We argue that the SGC offers a shared knowledge resource for drug discovery which is distinctive from other types of knowledge production and, as such, provides a knowledge infrastructure for the wider scientific community. We distinguish three ways in which this infrastructure functions as a model for investing in, extracting value from, and generating knowledge for the field. Our analysis suggests there is a future for open science models such as the SGC in health research and innovation, but that such models raise a set of challenges over the role of different public and private institutional actors and the way in which value is extracted

The importance of mentorship and collaboration for scientific capacity-building and capacity-sharing: perspectives of African scientists

Long-term goals for capacity-building in Africa centres around building a self-sufficient scientific community, however there is a lack of research on the interactions that are needed to make up a thriving academic community or the steps needed to realise such a goal. Through interviews with researchers supported by a capacity-building initiative, we have characterised their interactions with other scientists and the impact that these have on capacity-building. This has revealed a wide range of interactions that have not been captured by traditional bibliometric studies of collaboration and shown that a substantial amount of intra-African collaboration is taking place. This collaboration allowed the researchers to share capacity with their colleagues and this could provide an alternative to, or supplement, traditional North-South capacity-building. We have shown that this capacity-sharing can enable capacity to spill over from capacitybuilding programmes to the broader scientific community. Furthermore, researchers are deliberately hastening this capacitysharing through training or mentoring others outside of their capacity-building initiative, including those from more resource-poor groups. To understand how capacity-building initiatives can harness the power of these interactions, we investigated how interactions between researchers originated, and found that collaborations tended to be formed around pre-existing networks, with researchers collaborating with previous colleagues, or contacts formed through their mentors or consortium activities. Capacity-building organisations could capitalise on this through actions such as expanding mentorship schemes but should also ensure that researchers are not limited to pre-established networks but have exposure to a changing and growing pool of expertise. As interactions continue to move online since the appearance of COVID-19 this will present opportunities for new interaction patterns to develop. This study highlights the need to develop new metrics for collaboration that will take into account these new modes of interaction and the full range of interactions that make up a scientific community

Overburdening of peer review: A multi-stakeholder perspective on causes and effects

Peer review of manuscripts is labour-intensive and time-consuming. Individual reviewers might feel themselves overburdened with the amount of reviewing they are requested to do. Aiming to explore how stakeholder groups perceive reviewing burden and what they believe to be the causes of a potential overburdening of reviewers, we conducted focus groups with early-, mid-, and senior career scholars, editors, and publishers. By means of a thematic analysis, we aimed to identify the causes of overburdening of reviewers. First, we show that, across disciplines and roles, stakeholders believed that the reviewing burden is distributed unequally across members of the academic community, resulting in the overburdening of small groups of reviewers. Second, stakeholders believed this to be caused by (i) an increase in manuscript submissions; (ii) inefficient manuscript handling; (iii) lack of institutionalization of peer review; (iv) lack of reviewing instructions and (v) inadequate reviewer recruiting strategies. These themes were assumed to relate to an inadequate incentive structure in academia that favours publications over peer review. In order to alleviate reviewing burden, a holistic approach is required that addresses both the increased demand for and the insufficient supply of reviewing resources