Ethical and coordinative challenges in setting up a national cohort study during the COVID-19 pandemic in Germany

Abstract

With the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global researchers were confronted with major challenges. The German National Pandemic Cohort Network (NAPKON) was launched in fall 2020 to effectively leverage resources and bundle research activities in the fight against the coronavirus disease 2019 (COVID-19) pandemic. We analyzed the setup phase of NAPKON as an example for multicenter studies in Germany, highlighting challenges and optimization potential in connecting 59 university and nonuniversity study sites. We examined the ethics application process of 121 ethics submissions considering durations, annotations, and outcomes. Study site activation and recruitment processes were investigated and related to the incidence of SARS-CoV-2 infections. For all initial ethics applications, the median time to a positive ethics vote was less than two weeks and 30 of these study sites (65%) joined NAPKON within less than three weeks each. Electronic instead of postal ethics submission (9.5 days (Q1: 5.75, Q3: 17) vs. 14 days (Q1: 11, Q3: 26), p value = 0.01) and adoption of the primary ethics vote significantly accelerated the ethics application process. Each study center enrolled a median of 37 patients during the 14-month observation period, with large differences depending on the health sector. We found a positive correlation between recruitment performance and COVID-19 incidence as well as hospitalization incidence. Our analysis highlighted the challenges and opportunities of the federated system in Germany. Digital ethics application tools, adoption of a primary ethics vote and standardized formal requirements lead to harmonized and thus faster study initiation processes during a pandemic.

Keywords: COVID-19; Ethical approval; Ethics committee; Multicenter study; Pandemic preparedness; Study initiation.

Fig. 1

Ethics application process in NAPKON. *Germany has 17 medical state associations with specific regulations for the ethical consultation of physicians. Some ethics committees perform an in-depth review of each new study, while others accept the ethical approval of the primary ethics committee [23]. Bavaria is the only one not to require further ethics applications after the primary vote [24] ¹ with own university ethics committee; ² without own university ethics committee; SUEP = Cross-Sectoral Platform; HAP = High-Resolution Platform. Created with BioRender.com

Fig. 2

NAPKON ethics application overview. The organigram shows all considered ethics applications divided by platform, health care sector and type of application. SUEP = Cross-Sectoral Platform; HAP = High-Resolution Platform. Created with BioRender.com

Fig. 3

Time of initial ethics application processes. Applications are numbered and sorted according to the total time of the initial ethics application process. Initial ethics application processes are described for (a) 23 Cross-Sectoral Platform (SUEP) applications for university hospital ethics committees, (b) 12 SUEP applications for state medical association ethics committees, and (c) 11 High-Resolution Platform (HAP) ethics applications for university hospital ethics committees. The initial ethics vote of a state medical association applied in each case to the first nonuniversity site in the respective state. Ethics applications were submitted to 12 state medical associations. The following sites joined the vote

Fig. 4

Submission types for ethical approval. (a) Submission types for initial ethics applications at 35 university and state medical association ethics committees of the Cross-Sectoral Platform (SUEP) stated in absolute numbers. (b) Ethics application processing time according to the type of application (electronic or mail). Thirty-five initial applications and 63 amendment applications of the SUEP were considered (n = 98). Durations are shown in days from submission until the first response of the ethics committees

Fig. 5

The time until a final ethics vote was received for the Cross-Sectoral Platform (SUEP) and the High-Resolution Platform (HAP) study sites (n = 120) is shown in days with regard to the number of annotations: (a) zero (n = 80) vs. one or more (n = 40) annotations, (b) one to four (n = 21) vs. five or more (n = 19) annotations. For better visualization, the HAP study site outlier with 242 days of ethics process time was not included. Analysis containing this study site showed comparable significance levels

Fig. 6

Development of the number of activated study sites and patient recruitment in the Cross-Sectoral Platform (SUEP) and High-Resolution Platform (HAP). The number of recruited patients and activated study sites was added weekly and the time was given in calendar weeks of the period observed

Fig. 7

Correlation of hospitalization incidence in Germany and patient recruitment in the Cross-Sectoral Platform (SUEP, university (UK) and nonuniversity (NUK)) and High-Resolution Platform (HAP) study sites. Recruited patients per week are shown as stacked columns. The observation period is reported in calendar weeks. COVID-19 hospitalization incidence represents the mean number of hospitalizations due to COVID-19 infections per 100,000 inhabitants per calendar week in Germany. Waves are classified according to the specifications of the Robert Koch Institute [27] and visualized in different shades