A total of 134 RCTs (149,162 participants) were included (Figure S1;
Table S3). The median number of participants per trial was 205 (IQR,
729-203). A total of 55 RCTs were based in Western Europe, 22 RCTS in
North America, 35 RCTs were multiregional, and 32 RCTs were conducted in
rest of the world. Sixty RCTs were funded by academic center/university
or organization, 41 RCTs were industry funded, 17 RCTs were government
funded and 16 RCTs were conducted under collaboration between industry,
academic center/organization. Trends in age, representation of
women, race and ethnicity over time (1989-2019) are summarized in Table
1.
Overall representation of women was 35.2% (Table S4), which matched the
corresponding weighted proportion of women in epidemiological studies,
i.e. 35.1% (Figure-1). The representation of women varied from 26.2%
to 44.5% from 1989-2019 (P=0.30; Figure 2A; Table S4). Women
presentation was significantly higher in collaborative trials between
industry and universities/academic centers (36.1%), followed by
industry funded trials (34.8%) and government funded trials (33.8%)
(P<0.01). Women enrollment did not significantly differ based
on types of trials or baseline population. Linear regression did not
show a significant association between women enrollment in trials with
publication years (Figure S2).
The weighted mean age across the trials was 65.3±3.2 years which was
less than the corresponding weighted mean age of 71.1±4.5 years in the
comparative epidemiological data (Figure-1). Mean age of participants
was highest in North American RCTs (67.6±5.6 years) and lowest in RCTs
conducted in rest of the world (58.8±10.9 years) (P<0.01;
Table S4). Government funded RCTs (66.1±7.02 years) and industry funded
RCTs (66.7±5.7 years) had higher mean age as compared to academic
center/university-based RCTs (62.2±10.1 years) (P<0.01). In
stroke prevention RCTs, DOACs trials had lowest mean age (68.5±6.5
years), and watchman trials recruited participants with highest mean age
of 73.3±1.5 years (P<0.01). In AF treatment RCTs, trials with
different forms of pacing had patients with mean age of 69.1±5 years,
whereas, the mean age in trials assessing catheter ablation was 58.2±4.4
years (P<0.01).
Twenty-five RCTs reported distribution of patients according to age
groups (Table S6). In these trials, the proportion of older patients
(≥75 yrs.) was 36.1% which
was comparable to 34.8% weighted proportion in epidemiological data
(Figure 1). The distribution of older participants did not significantly
vary based on location of the trial, funding source, or baseline
population of the trials. Linear regression showed no significant
association between enrollment of older patients and publication years
(Figure S3).
RCTs conducted prior to 2007 lacked reporting on ethnic/racial
minorities and only 17 RCTs reported enrollment of ethnic/racial
minorities (Table S7). Among these RCTs, Hispanics represented 11.9%,
non-Whites 19.5%, Blacks 1.2%, Asians 14.2%, American Indian/Alaskan
natives 0.2%, and native Hawaiian/Pacific Islanders 0.05%. The
weighted proportions in the comparative data were: Hispanics 5.2%,
non-Whites 22.5%, 5.7% Blacks, 2.4% Asians, 0.1% native
Hawaiian/Pacific Islanders and 0.2% American Indian/Alaskan natives
(Figure-1).
In North American RCTs, representation of Hispanics was 0.3%,
non-Whites 0.4%, Blacks 0.2%, Asians 0.1% and both native
Hawaiian/Pacific Islanders and American Indians/Alaskan Natives was
<0.1%. None of the western European RCTs reported enrollment
with regards to ethnicity/races. There were no significant trends in
enrollment rates of ethnic/racial minorities in terms of funding
sources, baseline population or treatment strategies (Figure S3).