This thesis offers insights from knowledge management theory to understand the flow of knowledge across the multiple actors involved in the execution of a clinical trial in Latin America. In the last 12 years, the participation of Latin America in the business of clinical trials has significantly increased, becoming a highly demanded region to implement sponsored clinical research, overtaking regions like Africa, India, Southeast Asia, and Middle Eastern countries. Also, over this period, sponsors have increased the outsourcing of in-house activities such as trial monitoring, pharmacovigilance and regulatory services to Contracted Research Organisations (CROs), shifting the 'two organisations' and bi-directional relationship between the sponsor and the research sites. This change in the clinical trials landscape has also taken place in Latin America, where in addition to the CRO, the figure of Site Management Organisations (SMOs) has emerged to manage multiple research sites over the course of the trial. Therefore, the internationalisation of clinical research, plus the outsourcing of strategic activities, have transformed the implementation of clinical trials in the region. On the other hand, the results of a clinical trial depend strongly on the analytical skills and cognitive capabilities employed by people working on the project. These characteristics make the clinical trial a Knowledge Intensive Project (KIP), where the main project outcomes depend to a large extent on the use of knowledge by the workers, and the transfer of knowledge data and information across the multiple organisations working in the clinical trial. Because knowledge is the primary production factor in a clinical trial, and in the context of Latin America, to my knowledge, there is reduced research about the production of clinical evidence and the role of each one of the actors over the execution, the main research question that this thesis answers is: How does knowledge flow across organisations and is employed by people in their firms to implement the clinical trials and obtain their respective results? To answer this research question, I proposed and evaluated a three-step model to study the flow of knowledge, data and information across multiple organisations being part of the clinical trial and the use of these to produce the knowledge products by the sponsor and the research sites. This model has its roots in the literature of knowledge 'models, work and processes', the concept of interdependence and the literature of knowledge transfer and acquisition in the outsourced project. The model consists of three steps to address, at the inter-organisational level, the transfer and acquisition of knowledge, data and information and the interdependency on results; and at the intra-organisational level, the use of knowledge and storage. The presented model was evaluated and complemented based on the evidence collected through a multi-case study of three multi-organisational clinical trials to evaluate three new vaccine candidates in Colombia, Brazil and Mexico. The findings of this research indicated that the model was robust to study the flow of knowledge, data and information between the sponsor and the research sites, from the design of the protocol to the production of the clinical data. The results also indicate that the presence of intermediaries decreases the transfer of knowledge and information between the parts, and induces the selectivity of the research sites toward one of the sources of knowledge, the Sponsor, the CROs or SMO. The evidence shows that the acquisition of knowledge by physicians demands a knowledge-destruction capability to actively employ the acquired knowledge in the trial and the constant presence of loops to reinforce the knowledge acquisition. The empirical findings of knowledge and data acquisition by the research sites and the sponsor contributed to developing the concept of permeability, contributing to the literature of knowledge acquisition in outsourced projects. This research addresses, for the first time, the implementation of vaccine clinical trials in Latin America countries and the contribution of the local researcher to the project, especially with their knowledge about the communities intervened. But it also highlighted some of the aspects that affect the implementation of clinical trials, such as the labour conditions in academia, which induce turnover, and the lack of harmonisation among clinical trial regulation in the region. In conclusion, the model proposed allowed me to address simply the complexities that take place in the production of knowledge products in multi-organisational clinical trials in Latin America countries.

Bakgrund: Förordningen (EU) nr 536/2014 artikel 35 reglerar kliniska prövningar i akuta situationer. Lagen gäller inom EU/EES sedan januari 2022 och tillåter inkludering av kritiskt sjuka patienter med uppskjutet informerat samtycke, vilket innebär att den första prövningsspecifika interventionen görs innan försökspersonen eller deras juridiska ombud samtycker till deltagande i prövningen.  Syfte: Syftet med projektet är att beskriva de kliniska prövningar som sökts i akuta situationer sedan starten av den nya EU-förordningen om kliniska prövningar fram till den 15 september 2023. Metoder: Informationssystem för kliniska prövningar (CTIS) och konfidentiella databaser vid Läkemedelsverket användes för att samla in information om de sökta kliniska prövningarna enligt den nya förordningen. Resultat: Alla prövningar som definierats av sponsorn som involverade akuta situationer identifierades, omfattande 32 unika kliniska prövningar. Efter att ha analyserat ansökningsunderlagen och granskningar av medlemsstaterna, visade sig endast två tredjedelar av de inlämnade försöken involvera verkliga medicinska nödsituationer. En av dessa försöksansökningar avslogs, tre drogs tillbaka eller besvarades inte inom den maximala tiden för sponsorns feedback på frågor. Slutsatser: Den nya förordningen om kliniska prövningar tillåter forskning om akuta medicinska tillstånd som tidigare har varit uteslutna i de flesta EU/EES-medlemsstater. Det är viktigt för sponsorer att bekräfta att alla krav i artikel 35 är uppfyllda innan en klinisk prövning definieras som en klinisk prövning i en akut situation. Medlemsstaterna bör lära av varandra om hur rättsliga ombud för försökspersoner utses.