Comparison of plans for NMCB and MeCfs Lines with the research agenda

The ZonMw research programme received funding from the Minister for Medical Care Tamara van Ark, based on the ME/CFS research agenda drawn up in 2020.

Large support base

The research agenda was developed in collaboration between scientists and patient representatives, with the support of ZonMw. As ME/CFS Foundation Netherlands, we have been involved from the beginning and have agreed to this agenda. The same applies to other Dutch ME/CFS patient organizations. Because of this broad support in the patient community, we think it is important to evaluate the plans of the awarded consortia and projects based on the key requirements and desires stated in the agenda.

Target group and structure of cohort

Conditions: The agenda establishes that there is no gold standard to distinguish ME/CFS patients. Only rough boundaries can be indicated. The most commonly used diagnostic definitions are Fukuda/CDC, IOM, CCC, and ICC. The main goal of the program should be to improve the health and/or social position of patients, and for this, ME/CFS in all its complexity must be investigated. In individual studies, it will sometimes be very important to define the study population tightly. In other studies, it may be different. For example, in research aimed at providing better support for the diagnosis and possible sub-diagnoses, a broad inclusion will be required, including all characteristics associated with the (main) different diagnostic definitions. In replication studies, the old definition used in the original research must be taken into account.

The first requirement the agenda places on a patient cohort is that it is epidemiologically well-characterized. The cohort must be a good representation of the target population in terms of age, gender, and disease burden. It must also be large enough to draw statistically significant conclusions about subgroups. All participating patients will be checked to see if they meet the four known diagnostic definitions. Special attention must be paid to young people and seriously ill patients, as ME/CFS appears to develop differently in these groups.

Check: Both consortia, NMCB and MeCfs Lines, will build a biobank of ME/CFS patients with a cohort. This research infrastructure is set up in such a way that later projects can benefit from it. Given the conditions mentioned in the agenda, this can only be achieved with a broad inclusion of patients. It is difficult to say in general how many patients are needed for statistically valid statements, but for a heterogeneous cohort, this number appears to be around 600. Both consortia exceed this number.

The individual projects will use the consortium infrastructure and use different criteria sets for delimitation. Special provisions will be made to involve seriously ill patients in the research, and a separate registration will be made for adolescents. Both consortia meet these group requirements outlined in the agenda quite well.

Cooperation

Conditions: ME/CFS should be studied as a multisystem disease from various biomedical disciplines, with an emphasis on immunology, microbiology, neurology, cell biology, (epi)genetics, and cardiology. The projects should be interconnected with each other. International collaboration is also important, and there should be room for participation in a fellowship program.

Check: Both consortia are well-equipped to meet these requirements. They have also indicated that they will collaborate as much as possible. For example, protocols will be harmonized, and the two consortia will use the same symptom questionnaire.

Regarding international collaboration, we see a difference between the two consortia. The design of NMCB has parallels with that of ME/CFS patient cohorts abroad. Therefore, connections have been made with well-known European ME/CFS scientists such as Jonas Berqquist. The design of MeCfs Lines, which is based on a population cohort and has much more data available, is entirely new within the global ME/CFS field. Therefore, connections have been made with foreign scientists who have experience with this type of data-driven approach. We mention immunologist Thomas Vogl, who leads a research group at the Medical University of Vienna.

Research lines

Conditions: The agenda distinguishes between four categories of research lines. The category of practical and action research is outside the scope of this subsidy round, for which a separate round will be held later. That leaves three:

• Fundamental research
  o Chronic immune activation (e.g. after viral infections, host-microbe interactions and the microbiome in the digestive system)
  o Brain imaging (as with MRI)
  o Research into the energy balance in cells, linked to cell function
• Epidemiological research
  o Research into the origin of ME/CFS: an (epi)genetic basis of ME/CFS, the influence of environmental factors and research into infectious causes
  o Longitudinal study of the course of the disease
  o Research into a better description of ME/CFS, so that a better diagnosis can be made and subgroups and comorbidities can be identified
• Clinical research. Initially:
  o Mapping and testing of existing treatments to relieve symptoms, and testing of therapies known from other conditions
  o Research aimed at better diagnosis, such as exercise tests, biomarkers and research into antibodies in the blood

Check: Our organization has been involved with both consortia from the beginning. The two consortia, NMCB and MeCfs Lines, both create a solid foundation for conducting research along the lines mentioned above. NMCB is building a patient cohort from the ground up, making it ideal for both fundamental and clinical research. MeCfs Lines is building on data that has been collected since 2007 in Lifelines and thus has a lot of historical data, making it ideal for both fundamental and epidemiological research. The two consortia complement each other and together make the entire spectrum of desired research possible.

Conclusion

Our general conclusion is that both NMCB and MeCfs Lines meet all the important requirements. Together they provide an excellent infrastructure for the program, in which each type of research desired in the research agenda can be accommodated. If only one of the two would have been granted this would not have been the case.