The third educational seminar in the clinical trials meeting series arranged by CONNECT Working Group 2 took place via Zoom on 13 February 2023.
The topic was Industry-sponsored investigator-initiated studies – what does the protocol need to include to secure a good publication? The meeting was held in Norwegian and attracted 60 participants digitally.
Watch the recording of the meeting here:
Introducing the topic
Ravinder Singh, Director Clinical Research, International Oncology Medical Affairs, Eli Lilly and Aslaug Muggerud, Scientific Advisor Oncology, GSK moderated the meeting.
“The goal of this meeting is to describe success criteria for clinical trials initiated by academic researchers: from idea to high-impact publication. We also want to stimulate and motivate researchers to initiate studies with support from the industry,” said Ravinder Singh.
“Last meeting, we talked about the process for a researcher to get support from a pharmaceutical company for their idea of a study concept. In today’s meeting, we will talk about the process going forward, including the development and approval of the study protocol and contract, as well as the implementation of the study,” said Aslaug Muggerud.
Method is key
Jo Røislien, Professor in Medical Statistics at the Faculty of Health Sciences, the University of Stavanger, addressed two questions. The first was what needs to be included in the study protocol to lay the basis for a high impact publication.
“The methodology is incredibly important. We need good methods, so we can trust the results, and have good discussions, to reach the conclusions we have use for,” said Jo Røislien.
Secondly, Røislien addressed how innovative study designs can attract more clinical oncology studies to Norway.
“You need to have thought through what you are going to investigate. You need to identify precise questions. You also need to look for similar studies that are investigating comparable topics, and see if you can work together,” said Jo Røislien.
From idea to publication
Next, Jon Amund Kyte, Head, Department of Clinical Cancer Research, Senior consultant in oncology, Research Group Leader, Department of Cancer Immunology, Oslo University Hospital, presented the ALICE study as an example of a successful industry-supported study.
The ALICE study was a phase II study evaluating the combination of chemotherapy with checkpoint inhibitors in breast cancer patients. Roche supported the study with immunotherapy drugs. Jon Amund Kyte shared his learnings on successes and pitfalls on running the study.
“There was a great clinical need when we started this study and immunotherapy wasn’t an established therapy for this type of cancer. The results of the study showed that the addition of the checkpoint inhibitor to the chemotherapy improved progression free survival for these patients. The findings form the basis for the need for further studies into combining chemotherapy with checkpoint inhibitors.”
The results of the study were published in Nature Medicine in December 2022.
Ragnhild Sørum Falk, Head, Leader, Oslo Center for Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, also talked about the ALICE study and shared success criteria from a statistical and protocol perspective.
She mentioned several success criteria: “Early thorough discussions of the research questions matching the sample size calculation, understanding each other's languages, development of a detailed statistical analysis plan before unblinding, and truthfulness to the research question when interpreting the results. Forskningsstøtte gives free advising to all employees in the South-Eastern Norway Regional Health Authority,” said Falk.
The presentations were complemented with a panel discussion between Cathrine Notland, Medical Lead Oncology Norway, Pfizer, Ali Areffard, Disease Area Head Immune-oncology, Bristol Myers Squibb and Tarje Bergdahl, Country Medical Director Norway, Novartis Oncology. They addressed key issues researchers have to address when initiating and running successful industry-sponsored studies.
“Statistical, hierarchical models are more frequently used, which is interesting because you can identify which patient groups that will benefit i.e based on biomarkers and levels of their expression. We have seen this especially with PD-L1 expression for treatment with checkpoint inhibitors. Such approaches are efficient to faster identify patients that benefit in a study population,” said Ali Areffard.
“Having a concrete, specific research question is very important. It needs to be clearly defined beforehand. You also need to have a plan for how to mitigate challenges with patient inclusion, which almost always happen,” said Cathrine Notland.
“I want to highlight the clarity of the study’s design: ensure a logical relation between your objectives, and concrete questions, followed by the right endpoints and analysis, that can give you the answers needed. The next thing is the dimension of the study: plan for a size to result in clinical relevance, spread and meeting the end points. There is often a gap between the objective and the actual resources available,” said Tarje Bergdahl.
You can view the recordings of previous CONNECT educational seminars here: https://www.connectnorway.org/events#Recordingsofpastevents