Research into reasons and causes of excess mortality during the COVID-19 pandemic

Programme committee

• Committee members

  Chair

  prof. dr. L.J. (Louise) Gunning-Schepers

  Committee members

   prof. dr. M. (Marijn) de Bruin
  prof. dr. S. (Saskia) le Cessie
  prof. dr. R.H.H. (Rolf) Groenwold
  prof. dr. E. (Eelko) Hak
  dr. H.J. (Dika) Luijendijk
  prof. dr. A.E (Anton) Kunst
  dr. A. (Anja) Schreijer

• See the focus group

  Chair
  Prof. dr. R. (Robert) Verheij

  Vice chair
  Prof. dr. K. (Koos) van der Velden
  
  Members
  Prof. dr. A. (Agneta) Fischer
  Prof. dr. A. (Arfan) Ikram (tot 1 augustus 2022)
  Dr. D. (Dianne) de Korte-de Boer
  Prof. dr. E. (Eelco) Hak
  Dr. E. (Eline) van den Broek-Altenburg
  Prof. dr. F. (Frans) van Poppel
  Drs. H. (Hidde) Boonstra
  Dr. J. (Jan) von der Thüsen
  Prof. dr. K. (Koos) van der Velden
  Prof. dr. N. (Niek) Klazinga
  Prof. dr. P. (Pieter) van Baal
  Prof. dr. R. (Rein) Houben
  Prof. dr. R. (Ronald) Meester

Frequently asked questions and COVID-19

• Which studies into excess mortality and COVID-19 has ZonMw funded?

  To allow research into excess mortality to start as quickly as possible, a programme committee of independent experts drew up a research agenda concerning knowledge gaps, which have been categorised in 3 lines.

  Research agenda Excess mortality in the Netherlands

  • Line 1 consisted of a systematic literature review with international comparisons conducted by Cochrane Netherlands.
  • Line 2 consisted of research using available research and healthcare data. A list with all 11 studies awarded funding can be found here. This concerns relatively short studies with a duration of six months.
  • Within line 3, research was done with data, such as vaccination and test data, from the RIVM and GGDs.
• How were proposals for studies with available research data and healthcare data (line 2) assessed?
  • In the call for proposals 'Excess mortality in the Netherlands in the period 2020-2021_line 2', 13 research proposals were received and 12 of these were declared admissible. This means that 12 proposals were assessed against the predefined criteria of relevance and quality.
  • As a first step in the assessment, two committee members independently assessed each proposal. This assessment was recorded in an assessment report.
  • Subsequently, all proposals and the accompanying assessment reports were discussed in the committee meeting.
  • The committee's assessment was based on the assessment reports and the substantive discussion during the committee meeting. There are two options for each proposal:
    • Award: these applicants received an award letter. The committee could give recommendations to improve the project.
    • Hearing and rebuttal: the applicant received additional questions from the committee and was given the opportunity to respond to these in writing.
  • During the selection meeting on 27 October 2022, the committee advised the immediate awarding of 5 proposals. The remaining 7 applicants were invited to provide a rebuttal and received points of criticism from the committee to respond to. The committee discussed the rebuttals for these proposals during the second selection meeting on 1 December 2022. Each committee member prepared for all of the proposals for this meeting, unless there was a possible personal conflict of interests. During this meeting, the committee members advised awarding another 5 proposals funding. ZonMw accepted this advice and awarded 10 proposals.
  • For the other two proposals, one was rejected due to insufficient quality even though it received the qualification 'very relevant'. The final proposal was awarded funding on 21 December 2022, after an additional meeting with members of the committee. With this last award, the total number of projects awarded funding is 11.
• Criteria for awarding (or rejecting)

  The weighting of relevance and quality was carried out by means of the ranking matrix below. To be eligible for funding, a proposal had to receive the quality assessment 'good' or 'very good', and the relevance assessment 'relevant' or 'very relevant'. Please note: only proposals with an assessment  that falls in the blue spaces were awarded funding is 11.

  Afbeelding

  
• Who assessed the proposals?

  The proposals were assessed by an independent programme committee consisting of experts from the field. The composition of the committee is given here. The committee members, appointed by the ZonMw board, participated in the committee in their individual capacities as experts from their specific background. When putting the committee together, due consideration was given to the various areas of expertise: democracy, behaviour, statistics, epidemiology, geriatric medicine and health.

  Upon their appointment, the committee members stated that they would comply with and respect the ZonMw Code of Conduct on Conflicts of Interests in performing their work. Committee members with possible personal interests regarding a proposal do not assess that proposal and do not take part in the meeting when this proposal is being considered. The interests have been carefully mapped prior to the entire assessment process.

• Have any proposals been awarded that examine vaccination and excess mortality?

  This opportunity was provided. The relevance of this subject was stated, and the possibility for it was created in the research programme. An agenda was set at the beginning of the subprogramme Excess mortality. This agenda describes the various gaps in knowledge about excess mortality. It was drawn up in agreement between the programme committee, researchers from Statistics Netherlands and the RIVM, and members of the focus group. In this research agenda, one of the knowledge gaps described is: 'What are (modifiable) determinants of the (differences in) excess mortality related to vaccination (type of vaccine, vaccination behaviour, progression of vaccination rate, complications associated with vaccinations, vaccination design and booster programme)'.

  No proposals that examine vaccination and excess mortality have been awarded because none of the submitted proposals satisfied the quality requirements. In the period that the call for proposals 'Excess mortality in the Netherlands in the period 2020-2021_line 2' was open, the vaccination data and positive test data from the RIVM and municipal health services (GGDs) were not yet accessible for conducting independent research. In the 11 awarded studies, the researchers used the (healthcare) data available and accessible in October/November 2022. The data from the RIVM and GGDs became accessible on 18 November 2022. In the call for proposals 'Excess mortality in the Netherlands in the period 2020-2021_line 3' it was possible to make use of these data to investigate excess mortality.

• Why did ZonMw fund research into excess mortality and COVID-19?

  During the COVID-19 pandemic, more people died than expected. ZonMw therefore set up an in-depth research trajectory into the causes of this excess mortality at the request of the Ministry of Health, Welfare and Sport. Research results can contribute to preventing or reducing excess mortality during a next pandemic. The programme committee of independent experts has drawn up a research agenda concerning knowledge gaps that have been categorised in 3 lines.

  Research agenda excess mortality in the Netherlands

  • Line 1 consisted of a systematic literature review with international comparisons that will be conducted Cochrane Netherlands.
  • Line 2 consisted of research using available research and healthcare data. A list with all 11 studies awarded funding can be found here. This concerns relatively short studies with a duration of six months.
  • Within line 3, research was done with data, such as vaccination data and test data, from the RIVM and GGDs.
• How was the research agenda set?

  The research agenda was categorised in 3 lines to allow research into excess mortality to start as quickly as possible. The agenda was set on the basis of research questions that emerged in discussions between the programme committee and experts from the field. These are the researchers from Statistics Netherlands and the RIVM who do research into excess mortality, and the members of the focus group who supervise this research. The experts were asked to provide knowledge questions and research subjects. In addition, the programme committee also itemised which subjects fall under its own remit.

• Which proposals could be submitted in the funding round for line 3?

  Within line 3, research was funded that makes use of vaccination data and positive test data from the RIVM and GGDs. This data became accessible for carrying out independent research. Within this call for proposals, the main focus was on the substantiation of the quality of the data, the use of other models, correction for other co-variables, and other timeframes concerning follow-up. These studies were somewhat larger, with a maximum budget of 100,000 euros and a duration of 9 months. Researchers could submit their proposal for the call 'Excess mortality in the Netherlands in the period 2020-2021_line 3' until Tuesday, 31 January 2023.

• How was access to the vaccination and test data arranged?

  In the call for proposals, the focus was on line 3 of the research agenda. In this round, independent research was made possible using vaccination data from the RIVM and positive test results from the GGDs. On 18 November 2022, a Parliamentary Letter about COVID-19 explained that this data would be accessible for independent researchers from January 2023 onwards. During the previous funding round (line 2) this data was not yet accessible.

  Source: Statistics Netherlands
  Researchers must submit an application to Statistics Netherlands to obtain access to the vaccination data. Based on Article 41 of the Statistics Netherlands Act, the director-general of Statistics Netherlands is authorised to grant researchers access to a collection of data for the purpose of statistical or scientific research. In this, Statistics Netherlands has the legal obligation to take measures to prevent the recognition of individual persons, households, businesses or institutions. On the basis of Article 42 of the Statistics Netherlands Act, the director-general only grants a request to access on the basis of Article 41 of the Statistics Netherlands Act if, in the opinion of that director-general, the applicant has taken sufficient measures to prevent that the collection of data will be used for purposes other than statistical or scientific research. Research institutes need to have an authorisation (Application for access to microdata (cbs.nl)) to obtain access to the remote access environment of Statistics Netherlands.

• What was the timeline of research into excess mortality and COVID-19?

  Activity	Start date	End date
  Call for proposals line 2 open	11-08-2022	30-09-2022
  • 12 admissible proposals submitted
  Assessment committee meeting	27-10-2022	27-10-2022
  Outcome assessment committee meeting: • 5 projects awarded funding • 7 projects rebuttal
  Applicants' rebuttal	07-11-2022	25-11-2022
  Assessment meeting rebuttal	01-12-2022	01-12-2022
  Outcome assessment committee meeting: • 5 projects awarded funding • 1 proposal rejected • 1 proposal additional rebuttal
  Interview additional rebuttal	21-12-2022	21-12-2022
  Call for proposals line 3 open	15-12-2022	31-01-2023

• Which research into vaccination and COVID-19 did ZonMw fund?

  ZonMw has commissioned various studies into COVID-19 vaccination among people with a compromised immune system. These studies supplemented the vaccination studies of the RIVM, vaccine manufacturers and international researchers and organisations. At the start of 2021, within the subprogramme Vaccine studies, a network was set up of 8 studies into the optimal use of COVID-19 vaccines in patients with a compromised or weakened immune system (immunodeficiency). The results from these studies have been included in various advisory reports of the Health Council of the Netherlands and have therefore contributed to the Dutch vaccination policy. The results have, amongst other things, revealed that these patients can be safely vaccinated and that a number of patient groups exhibit a good antibody response following vaccination. After two vaccinations, these patients are sufficiently protected against the severe consequences of a COVID-19 infection.

  Conversely, there were various patient groups for whom two vaccinations against COVID-19 had an insufficient effect as yet. These patients made insufficient or no antibodies and immune cells and were therefore insufficiently protected against COVID-19. Extra booster vaccinations ensured that a number of these patients acquire a better protection. Follow-up research is ongoing into the effect of repeated boosters and lasting protection by means of vaccination in this vulnerable group of patients. For this, the 8 studies are collaborating with the RIVM and use harmonised protocols to realise the research that renders overarching analyses possible. With this approach, researchers also hope to gain more insight into the correlates of (long-term) protection through vaccination.

• Why did ZonMw decide to commission research into excess mortality and COVID-19?

  On 1 December 2021, Dutch parliamentarian Pieter Omtzigt submitted a motion to request that the government, as soon as possible, commission scientific research into the reasons for the causes of excess mortality in 2020-2021.

• How up to date were the vaccination data?

  Source: Statistics Netherlands
  Statistics Netherlands receives monthly vaccination data from CIMS, the COVID Information and Monitoring System of RIVM, in which recent changes are implemented. With these, an up-to-date picture of changes in the database is obtained. As described in the Data Protection Impact Assessment (DPIA), changes are regularly implemented in the database with vaccination data. This happens, for example, when people have received a new vaccine or modified their consent to use their data for research. By comparing the databases with each other each month, insight is obtained into which changes have occurred over the course of time (including the decease of people).

• Which variables did the vaccination data contain?

  Source: Statistics Netherlands
  The variables that the vaccination data contain are described in a 'Data Protection Impact Assessment (DPIA), supply COVID-19 vaccination data by RIVM to Statistics Netherlands', and are identical to the variables that were used in 2022 for the research into excess mortality by the RIVM and Statistics Netherlands. This concerns: citizen service number (BSN), sex, year of birth, vaccine name, vaccination date, vaccine batch, administering organisation, booster code and serial number. The microdata catalogue of Statistics Netherlands contains the specifications of the included data that it has made available (Catalogue microdata (cbs.nl)). The vaccination history at the level of the individual can be supplemented with other data present at Statistics Netherlands, such as possible use of healthcare, date of death and cause of death. All deceased persons have also been included in the CIMS databases. The DPIA recently drawn up by Statistics Netherlands has been adjusted to clarify the text about this.

• Could researchers obtain access via Statistics Netherlands to all data necessary for research into excess mortality?

  Source: Statistics Netherlands
  Statistics Netherlands possesses various sources of data necessary for research into excess mortality and, under strict conditions, makes these available for scientific research. However, Statistics Netherlands does not possess all possible relevant data sources researchers might want to use. This can sometimes be due to legal reasons. However, under certain conditions, researchers are allowed to bring their own data into the remote access environment.