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HASIL REVIEW

JUDUL Quantifying the Effect of Public Activity Intervention Policies

on COVID-19 Pandemic Containment Using Epidemiologic
Data From 145 Countries

PENULIS Jichao Sun,Yefeng Zheng, Wenhua Liang, Zifeng Yang, Zhiqi

Zeng, Tiegang Li, Junjie Luo, Man Tat Alexander Ng,
MBChB, MPH, Jianxing He, Nanshan Zhong.

NAMA JURNAL ELSEVIER

TAHUN TERBIT 2021

LATAR BELAKANG Hingga Juli 2021, sindrom pernafasan akut parah coronavirus
DAN RESEARCH GAP 2, yang menyebabkan penyakit coronavirus 2019 (COVID-19),
masih menyebar secara global. Intervensi nonfarmasi
tampaknya menjadi cara penting yang dapat mengurangi
penularan virus sampai rejimen pengobatan yang efektif atau
imunisasi massal tersedia. Strategi intervensi ini termasuk
pengawasan cepat, karantina, dan langkah-langkah jarak fisik
seperti penutupan sekolah dan tempat kerja, pembatasan
perjalanan internal dan eksternal, dan persyaratan tinggal di
rumah. Hampir semua negara telah mengadopsi serangkaian
kebijakan penahanan dan penutupan pada titik waktu yang
berbeda, dan beberapa tampaknya telah menahan penularan
virus dengan berbagai tingkat keberhasilan. Namun demikian,
bukti kuantitatif tentang efektivitas kebijakan intervensi yang
berbeda tidak konsisten.
Sebagian besar studi awal menerapkan asumsi pemodelan
menggunakan data dalam satu negara untuk menguji efektivitas
intervensi. Misalnya, Lai dkk mengembangkan kerangka
simulasi menggunakan jaringan perjalanan harian di seluruh
China. Mereka memperkirakan tanpa intervensi nonfarmasi,
kasus COVID-19 kemungkinan akan meningkat 67 kali lipat.
Kelompok penelitian lain mengembangkan model rentan-
 terpapar-infeksi-dihapus terstruktur usia dengan data dari kota-
kota berukuran sedang di Amerika Serikat, menunjukkan
bahwa intervensi yang dimulai lebih awal dalam epidemi
menunda kurva epidemi dan intervensi yang dimulai kemudian
meratakan kurva epidemi. Namun demikian, hasil tersebut
berasal dari asumsi matematis di bawah skenario dugaan dan
dengan demikian tidak dapat diverifikasi.
Data dari masing-masing negara mengalami ketidakmampuan
intrinsik dalam mengukur dan membandingkan efek dari
intervensi yang berbeda. Sekarang, bukti dari analisis
komparatif menggunakan data dari beberapa negara masih
tidak konsisten. Masalah utama dalam menganalisis hubungan
kausal adalah bahwa ada pembaur yang tidak teramati seperti
kapasitas pengujian yang berbeda dari waktu ke waktu dan
heterogenitas di seluruh negara. Studi empiris sebelumnya
memanfaatkan metode statistik langsung gagal untuk
mengatasi masalah ini. Pada awal Juli 2020, dengan sebagian
besar negara Asia dan Eropa mencapai tahap akhir dari
gelombang epidemi pertama dan ketersediaan informasi
intervensi yang terperinci, kami dapat secara retrospektif
meneliti efek intervensi menggunakan metode statistik yang
lebih canggih. Dalam studi ini, kami melakukan analisis
komprehensif tentang efektivitas ketepatan waktu, keketatan,
dan durasi dari 8 kebijakan intervensi publik tentang
penahanan COVID-19 menggunakan data dari negara-negara
di seluruh dunia. Selain itu, kami memperkenalkan estimator
kontrafaktual baru berdasarkan data epidemi COVID-19 deret
waktu untuk mengukur efek dari berbagai intervensi dengan
bias yang lebih sedikit.

TEORI DAN - Kebijakan yang kami minati adalah intervensi penahanan

VARIABEL YANG dan penutupan termasuk 8 rejimen, yaitu, penutupan
DIGUNAKAN sekolah, penutupan tempat kerja, pembatalan acara publik,
pembatasan pertemuan, penutupan transportasi umum,
persyaratan tinggal di rumah, pembatasan pergerakan
internal, dan pengendalian perjalanan internasional.
Masing-masing dari 8 intervensi dicatat dalam skala ordinal
yang mewakili tingkat keketatan kebijakan.
- Kami memilih negara dengan rangkaian waktu lebih dari
90 hari dan jumlah infeksi kumulatif. 100 untuk
mengurangi ketidakpastian. Kami mengkodekan masing-
masing dari 8 intervensi menjadi 3 variabel independen
(Tanggal Mulai, Keketatan, dan Durasi). Tanggal Mulai
dicatat sebagai hari dimulainya intervensi relatif terhadap
100 kasus pertama yang terjadi di negara tersebut, yang
menjadi indikator respons tepat waktu terhadap pandemi.
Kami memilih tanggal 100 kasus pertama daripada kasus
pertama sebagai titik awal karena deteksi kasus pertama
tunduk pada lebih banyak keacakan yang mungkin
menimbulkan gangguan substansial dalam analisis berikut.
 Keketatan diukur sebagai tingkat keketatan rata-rata
sepanjang hari selama fase epidemi tertentu.
- Model Imperial College London ini adalah salah satu
pendekatan yang paling banyak digunakan untuk estimasi
infeksi yang sebenarnya dan telah direkomendasikan oleh
Our World in Data untuk mempelajari efek kebijakan.
Singkatnya, model tersebut menyesuaikan data tentang
kematian yang dikonfirmasi dengan menggunakan
perkiraan tingkat kematian akibat infeksi untuk
“menghitung kembali” berapa banyak infeksi yang akan
terjadi selama minggu-minggu sebelumnya untuk
menghasilkan jumlah kematian tersebut. Ini juga
memperhitungkan data tingkat mobilitas dan pengujian
menurut negara jika tersedia di bawah berbagai asumsi dan
pengetahuan epidemiologi untuk menghasilkan perkiraan
infeksi yang kurang bias.

RUMUSAN MASALAH Bagaimana mengatasi negara yang telah mengadopsi kebijakan

intervensi aktivitas publik untuk mengendalikan pandemi
penyakit coronavirus 2019 (COVID-19). Namun demikian,
bukti empiris efektivitas intervensi yang berbeda pada
penahanan epidemi tidak konsisten?

POPULASI DAN - intervensi pada fase awal (periode pertumbuhan lambat)

SAMPEL berkorelasi negatif dengan hasil, dengan beberapa di
antaranya menunjukkan signifikansi (Meja 2). Namun
demikian, selama fase tengah (fase pertumbuhan cepat),
Ketegangan dan Durasi sebagian besar berkorelasi positif
dengan hasil. Durasi rata-rata fase awal untuk semua
negara adalah 61 hari. Kami melakukan analisis lebih lanjut
dengan menghitung Keketatan dan Durasi di bulan pertama
dan bulan kedua epidemi, masing-masing. Hasil serupa
ditemukan bahwa variabel Keketatan dan Durasi pada
bulan pertama sebagian besar negatif, sedangkan pada
bulan kedua sebagian besar positif, terkait dengan infeksi
kumulatif.
- COVID-19 sebelum dan sesudah pelaksanaan 8 intervensi
disajikan dalam Gambar 2. Secara keseluruhan, pola serupa
yang konsisten diamati untuk semua intervensi
yangRtmenurun perlahan sebelum intervensi, namun
setelah intervensi,Rtmenurun dengan cepat dalam 7 sampai
14 hari, dan tren penurunan melemah sesudahnya.
konvergen menjadi sekitar 1 dalam waktu sekitar 30 hari
setelah intervensi. Secara keseluruhan, rata-rataRtmenurun
sebesar 6,7% (95% CI 4,8-12,4) pada 7 hari dan sebesar
 17,0% (95% CI 7,8-29,1) pada 14 hari setelah salah satu
intervensi.
- Dalam kebanyakan kasus, perkiraan efek rata-rata sekitar
nol pada periode pra-intervensi dan menurun dengan cepat
hingga di bawah nol dalam 7 hingga 14 hari setelah
intervensi, ke nilai minimumnya (berkisar dari20,52
sampai20,08 dengan median20,30) dalam 25 hingga 32 hari
( Gambar 3). Ini sesuai dengan pengurangan maksimum
22% hingga 41% dalam Rt.Di antara 8 intervensi,
penutupan sekolah, penutupan tempat kerja, dan
pembatalan acara publik menunjukkan bukti asosiasi yang
paling kuat dan paling konsisten.

METODE PENELITIAN Kami menemukan bahwa implementasi awal dari semua

/ ANALISIS kebijakan penahanan dikaitkan dengan pengurangan kasus
infeksi. Temuan ini seperti yang diharapkan dan sejalan dengan
sebagian besar penelitian sebelumnya.13,29-31 Bersamaan
dengan temuan ini, kami juga menemukan beberapa bukti
bahwa keketatan yang lebih tinggi dan durasi yang lebih lama
dari beberapa kebijakan penahanan pada tahap pertumbuhan
awal atau lambat berkorelasi dengan penurunan kasus infeksi.
Namun demikian, hasil dari tahap pertumbuhan menengah atau
cepat menunjukkan bukti asosiasi positif. Ini adalah temuan
baru yang tidak dibahas oleh penelitian sebelumnya. Hubungan
positif antara Keketatan dan Durasi intervensi di tahap tengah
dan infeksi total mungkin dikaitkan dengan kausalitas terbalik,
yang berarti bahwa beberapa negara memperkuat dan
memperpanjang intervensi dalam menghadapi situasi yang
lebih parah.
Baru-baru ini, varian baru sindrom pernafasan akut parah
coronavirus 2, terutama varian Delta yang lebih banyak
menular dari strain aslinya, menyebar dengan cepat di beberapa
negara seperti India dan Amerika Serikat. Bukti mengenai
apakah kebijakan intervensi pemerintah efektif dalam
membendung varian baru masih langka karena sebagian besar
negara telah melonggarkan pembatasan aktivitas publik.
Namun demikian, wabah regional varian Delta baru-baru ini
menyerang Guangzhou dan Shenzhen di China dari Mei 2021
hingga Juni 2021. Pemerintah daerah segera memberlakukan
tindakan kontrol yang ketat sejak identifikasi kasus baru
pertama, termasuk pembatalan acara publik, penutupan tempat
kerja yang tidak perlu, dan pelacakan kontak Wabah regional
berhasil dikendalikan dalam waktu satu bulan, mencegah
limpahan virus dan penyebaran skala besar.32Sebaliknya,
negara-negara yang tidak menerapkan langkah-langkah
penahanan yang ketat sejak awal mengalami wabah domestik
yang tidak terkendali.33Ini memberi kita beberapa bukti awal
bahwa intervensi awal dan ketat efektif dalam mengendalikan
wabah varian baru. Mengingat transmisi yang kuat dari varian
 baru, pemerintah harus menerapkan langkah-langkah
pengendalian agresif sedini mungkin, meskipun tingkat
pertumbuhan mungkin sangat lambat di negara mereka pada
periode awal. Tampaknya sudah terlambat untuk
memperbaikinya ketika tiba pada tahap pertumbuhan cepat.

HASIL DAN - Hasil pertama adalah perkiraan infeksi kumulatif per juta
PEMBAHASAN penduduk untuk setiap negara pada 1 Juli 2020. Hasil ini
digunakan untuk menyelidiki korelasi dengan variabel
intervensi yang berbeda. Kami memilih 1 Juli 2020,
sebagai titik akhir karena sebagian besar negara Asia dan
Eropa telah mencapai akhir gelombang epidemi pertama
mereka pada akhir Juni atau awal Juli 2020.
- Hasil kedua adalah bilangan reproduksi yang berubah-ubah
terhadap waktu (Rt) untuk setiap negara pada setiap
hari.Rtadalah ukuran yang mewakili jumlah rata-rata kasus
sekunder yang terinfeksi oleh 1 kasus indeks. Kami
menggunakan medianRtperkiraan dari model EpiForecasts
yang banyak digunakan (https://epiforecasts.io). Proses
estimasi didasarkan pada kasus dan kematian yang
dikonfirmasi sambil memperhitungkan ketidakpastian masa
inkubasi, penundaan infeksi hingga konfirmasi, dan
penundaan infeksi hingga kematian. Cara
menghitungnyaRttelah dirinci dalam Cori et al. Singkatnya,
tingkat penularan COVID-19 dapat diperkirakan dengan
rasio antara infeksi baru atau kematian pada suatu
waktutdan orang-orang yang menularkan pada saat itut -
ddi manadadalah penundaan infeksi hingga konfirmasi
sebelumnya atau penundaan infeksi hingga kematian yang
sesuai.
- Secara keseluruhan, data deret waktu dari kebijakan
intervensi diambil untuk 178 negara pada 1 Juli 2020, dari
Oxford COVID-19 Government Response Tracker. Setelah
pengecualian, total 145 negara dimasukkan dalam
penelitian ini. Jumlah negara di berbagai benua adalah
sebagai berikut: 36 di Eropa, 36 di Asia, 47 di Afrika, 13 di
Amerika Utara, 11 di Amerika Selatan, dan 2 di Oseania.
Infeksi kumulatif per juta penduduk pada 1 Juli berkisar
antara 46 (Burundi) hingga 212154 (Peru), dengan nilai
median 9867 (kisaran interkuartil 2655-30581).
- Dalam studi ini, kami menemukan beberapa bukti bahwa
implementasi lebih awal, durasi yang lebih lama, dan
kebijakan penahanan yang lebih ketat pada tahap awal
tetapi tidak pada tahap tengah dikaitkan dengan penurunan
infeksi COVID-19. Dengan estimator kontrafaktual baru,
kami dapat mengontrol pembaur waktu yang tidak teramati,
menghasilkan hubungan sebab akibat yang lebih andal.
Hasil kami menunjukkan bahwa kebijakan intervensi
pemerintah dikaitkan dengan penurunan 22% hingga 41%
 dalam penularan COVID-19 dalam waktu sekitar 25 hingga
32 hari setelah penerapannya.

ALASAN MENGAPA Karena artikel ini membahas bagaimana menggunakan data

ARTIKEL INI epidemiologi dari 145 negara, yang menemukan beberapa
RELEVAN DAN bukti bahwa implementasi kebijakan penahanan yang lebih
PENTING DALAM awal, lebih ketat, dan lebih lama pada tahap awal dikaitkan
KAITAN dengan penurunan kasus yang terinfeksi. Temuan tersebut akan
TOPIK/MATERI memiliki implikasi penting bagi pemerintah untuk
PEMBELAJARAN memberlakukan atau mencabut kebijakan penahanan dalam
memerangi gelombang wabah COVID-19 saat ini dan di masa
depan. Studi di masa depan harus menekankan pada bagaimana
menambahkan dan menghapus kebijakan intervensi
mempengaruhi penularan virus, terutama mutan barunya
seperti varian Delta, untuk pengambilan keputusan tentang
pencabutan kebijakan penahanan.
REVIEW ATAS Artikel ini memberikan bukti yang lebih andal tentang efek
ARTIKEL INI kuantitatif dari intervensi kebijakan pada epidemi COVID-19
dan menyarankan bahwa intervensi aktivitas publik yang lebih
ketat harus diterapkan pada tahap awal epidemi untuk
meningkatkan penahanan. Ada beberapa bukti bahwa
implementasi lebih awal, durasi yang lebih lama, dan kebijakan
intervensi yang lebih ketat pada tahap awal tetapi tidak pada
tahap menengah dikaitkan dengan penurunan infeksi COVID-
19. Model kontrafaktual terbukti telah mengendalikan pembaur
bervariasi waktu yang tidak teramati dan menetapkan
hubungan sebab akibat yang valid antara intervensi kebijakan
danRt pengurangan. Efek intervensi rata-rata mengungkapkan
bahwa semua intervensi menurun secara signifikanRtsetelah
implementasi mereka.Rtmenurun 30% (22%-41%) dalam 25
hingga 32 hari setelah intervensi kebijakan. Di antara 8
intervensi, penutupan sekolah, penutupan tempat kerja, dan
pembatalan acara publik menunjukkan bukti asosiasi yang
paling kuat dan paling konsisten.
*Lampirkan jurnal yang menjadi acuan
LAMPIRAN JURNAL:

Quantifying the Effect of Public Activity Intervention Policies on COVID-19 Pandemic

Containment Using Epidemiologic Data From 145 Countries
Jichao Sun, PhD,* Yefeng Zheng, PhD,* Wenhua Liang, PhD,* Zifeng Yang, PhD,* Zhiqi Zeng, PhD,*
Tiegang Li, PhD,

Junjie Luo, PhD, Man Tat Alexander Ng, MBChB, MPH, Jianxing He, PhD, Nanshan Zhong, PhD

ABSTRACT

Objectives: Most countries have adopted public activity intervention policies to control the coronavirus disease 2019 (COVID19)
pandemic. Nevertheless, empirical evidence of the effectiveness of different interventions on the containment of the epidemic was
inconsistent.
Methods: We retrieved time-series intervention policy data for 145 countries from the Oxford COVID-19 Government Response Tracker
from December 31, 2019, to July 1, 2020, which included 8 containment and closure policies. We investigated the association of
timeliness, stringency, and duration of intervention with cumulative infections per million population on July 1, 2020. We introduced a
novel counterfactual estimator to estimate the effects of these interventions on COVID-19 time-varying reproduction number (Rt).
Results: There is some evidence that earlier implementation, longer durations, and more strictness of intervention policies at the early
but not middle stage were associated with reduced infections of COVID-19. The counterfactual model proved to have controlled for
unobserved time-varying confounders and established a valid causal relationship between policy intervention and Rt reduction. The
average intervention effect revealed that all interventions significantly decrease Rt after their implementation. Rt decreased by 30%
(22%-41%) in 25 to 32 days after policy intervention. Among the 8 interventions, school closing, workplace closing, and public events
cancellation demonstrated the strongest and most consistent evidence of associations.
Conclusions: Our study provides more reliable evidence of the quantitative effects of policy interventions on the COVID-19 epidemic
and suggested that stricter public activity interventions should be implemented at the early stage of the epidemic for improved
containment.

Keywords: COVID-19, effectiveness, public health intervention.

VALUE HEALTH. 2021; -(-):-–-

Introduction surveillance, quarantine, and physical distancing

measures such as school and workplace closing,
As of July 2021, the severe acute respiratory
internal and external travel restrictions, and stay
syndrome coronavirus 2, causing the
at home requirements.4-7 Almost all countries
coronavirus disease 2019 (COVID-19), is still
have adopted a series of containment and
spreading globally.1 The nonpharmaceutical
closure policies at different time points, and
interventions appear to be an important way
some seem to have curbed the virus
that could reduce virus transmission until
transmission with varying degrees of success. 8-10
effective treatment regimens or mass
Nevertheless, the quantitative evidence on the
immunizations are available.2,3 These
effectiveness of different intervention policies
intervention strategies include swift
has been inconsistent.
Most early studies applied modeling
assumptions using data within a single country
to examine the effectiveness of in-
terventions.6,9-13 For example, Lai et al12
developed a simulation framework using daily
travel networks across China. They estimated
that without nonpharmaceutical interventions,
the COVID19 cases would likely have increased
67-fold. Another research group developed an
age-structured susceptible-exposed-infectious-
removed model with data from medium-sized
cities in the United States, suggesting that
interventions that started earlier in the
epidemic delayed the epidemic curve and
interventions that started later flattened the
epidemic curve.13 Nevertheless, those results
were derived from mathematical assumptions
under presumptive scenarios and thus could not
be verified.
Data from individual countries suffered from its
intrinsic incapability in quantifying and
comparing the effects of different interventions.
By now, evidence from comparative analysis
*Jichao Sun, Yefeng Zheng, Wenhua Liang, Zifeng Yang, and Zhiqi Zeng contributed equally to this work.
1098-3015/$36.00 - see front matter Copyright ª 2021, ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc.
using
data from multiple countries is still inconsistent.
The major issue in analyzing the causal
relationships is that there exist unobserved
confounders such as different testing capacities
over time and heterogeneity across countries.
Previous empirical studies leveraging
straightforward statistical methods failed to
address this problem.14,15 By early July 2020,
with most Asian and European countries
reaching the late stage of the first epidemic
wave and the availability of detailed
intervention information, we were able to
retrospectively scrutinize the effects of
interventions using more sophisticated
statistical methods. In this study, we performed
a comprehensive analysis of the effectiveness of
the timeliness, stringency, and duration of 8
public intervention policies on COVID-19
containment using data from worldwide
countries. Moreover, we introduced a novel
counterfactual estimator based on the time-
series COVID-19 epidemic data to quantify the
effects of different interventions with less bias.
Methods
Data Sources and Selection
The daily confirmed cases for COVID-19 of each
country were retrieved from
https://ourworldindata.org from December 31,
2019, to July 1, 2020. The data were collected
and reported by the health authority of each
country. The country-based time-series data for
the containment and closure policies were
retrieved from the Oxford COVID-19
Government Response Tracker (https://
github.com/OxCGRT/covid-policy-tracker)
during the same time period. Details of the data
collection and annotation have been described
in a working article.16 In brief, a group of policy
and government experts routinely collected
information on public policies worldwide,
including containment and closure
interventions, and economic and healthcare
supports. The policies of our interest were
containment and closure interventions including
8 regimens, namely, school closing, workplace
closing, public events cancellation, restrictions
on gatherings, public transport closing, stay at
home requirements, restrictions on internal
movement, and international travel controlling.
Each of the 8 interventions was recorded on an
ordinal scale representing the level of strictness
of the policy. Take workplace closing for
example, 0 represents no measures; 1
represents recommending closing; 2 represents
requiring closing for some sectors or categories
of workers; and 3 represents requiring closing
(or work from home) for all-but-essential
workplaces. We selected countries with a time
series longer than 90 days and the number of
cumulative infections . 100 to reduce
uncertainties. We coded each of the 8
interventions into 3 independent variables
(StartDate, Stringency, and Duration). Start-Date
was recorded as the days of intervention
commencement relative to the first 100 cases
occurrence in that country, which served as an
indicator for timely response to the pandemic.
We selected the date of the first 100 cases
instead of the first case as the start point
because the detection of the first case was
subject to more randomness that might
introduce substantial noise in the following
analysis. Stringency was measured as the
average level of strictness across all days during
a certain epidemic phase. Duration was
measured as the number of days under
intervention divided by the number of total days
during a certain epidemic phase.
Outcomes
The first outcome was the estimated cumulative
infections per million population for each
country on July 1, 2020. This outcome was used
to investigate the correlations with different
intervention variables. We chose July 1, 2020, as
the endpoint because most Asian and European
countries had reached the end of their first
epidemic waves by late June or early July 2020
(see Appendix Fig. 1 in Supplemental Materials
found at https://doi.org/10.1016/j.
jval.2021.10.007). During this period, some
governments lifted policy restrictions and the
public loosened precautions, which in certain
cases led to the resurgence of cases and deaths
subsequently. Then, the governments
reimposed policies in a policy seesaw as the
epidemic waxed and waned.17,18 The lift and
reimposition of policies and resurgence of the
epidemic would affect the estimation of
intervention effects. We aim to study the effect
of policies within a single epidemic wave, with
the consideration of reducing confounding and
uncertainty. Nevertheless, there is no precise
and consistent cutoff date for all countries.
Therefore, we performed additional sensitivity
analyses, by altering the cutoff date 1 month
earlier (June 1, 2020) or later (August 1, 2020),
to test the robustness of the results. The
number of reported cases represents a
straightforward metric reflecting the severity of
the pandemic and has been widely used in
previous articles for
comparison between countries.19,20
Nevertheless, the metric has limitations because
the testing and reporting strategies are different
across countries. In the current study, we chose
the number of true infections rather than the
number of reported cases as the metric for
comparison. Given that the true infections were
not known, we referred to the age-structured
susceptibleexposed-infectious-removed model
(https://github.com/mrc-ide/ squire) developed
by Imperial College London to estimate true
infections. This Imperial College London model
is among the most widely used approaches for
estimations of true infections and has been
recommended by Our World in Data for
studying policy effects. In brief, the model fit
data on confirmed deaths by using an estimated
infection fatality rate to “back-calculate” how
many infections would have occurred over the
previous weeks to produce that number of
deaths. It also accounted for mobility and
testing rates data by country if available under a
range of assumptions and epidemiological
knowledge to generate a less biased infection
estimate.
The second outcome was the time-varying
reproduction number (Rt) for each country on
each day. Rt is a measurement that represents
the mean number of secondary cases that were
infected by 1 index case. We used the median Rt
estimates from the widely used EpiForecasts
model (https://epiforecasts.io). The process of
estimation was based on confirmed cases and
deaths while accounting for uncertainties of the
incubation period, the infection-to-confirmation
delays, and the infection-to-death delays. The
method of calculating Rt has been detailed in
Cori et al.21 In brief, the transmission rate of
COVID-19 can be estimated by the ratio
between new infections or deaths at time t and
the infectious people at time t - d where d is the
previous infection-toconfirmation delays or the
infection-to-death delays as appropriate.
The missing data (ie, confirmed cases or policy
intervention) in the middle of time series were
linearly interpolated using nonmissing
observations.
Correlation Analysis
We conducted Spearman rank correlation
analysis between Start-Date variable of each
intervention and cumulative infection numbers
using paired data from countries, to test
whether the delayed policy implementation was
associated with more infected cases. We chose
Spearman rank correlation because the Start-
Date variable (also the Stringency and Duration
variables) has a highly skewed distribution. The
correlation coefficient ranging from 21 to 1 is a
statistical measure of the strength of a
monotonic relationship between 2 variables. We
also draw boxplots of the outcome by tertiles of
Start-Date to examine the monotonic
relationship. Because countries hit by the
epidemic later may implement interventions
timelier in view of the outbreaks in other
countries, we performed an additional partial
correlation analysis that was adjusted for the
absolute date of first case occurrence.
We investigated the Spearman rank correlations
of cumulative infection numbers with Stringency
and Duration of interventions, separately at the
early and middle stages of the epidemic. We
adopted an approach proposed in a previous
article22 that divided the progression curve of
COVID-19 into the early slow growth phase, the
middle fast growth phase, and the late steady
phase, using a data-driven phenomenological
logistic model. The slope of the curve represents
the rate of epidemic growth, which is used to
divide different phases. Examples of the fitted
curves and phase cutoffs are shown in Appendix
Fig. 2 in Supplemental Materials found at
https://doi.org/10.1016/j.jval.2021.10.007. For
sensitivity analysis, we alternatively defined the
early phase as the first month since the first
confirmed case occurrence for each country.
Counterfactual Effect Estimates
First, we compared the trends in the Rt before
and after the implementation of each
intervention for descriptive purpose. We
calculated the mean value (95% confidence
intervals [CIs]) of the Rt for all countries on
different days relative to intervention
implementation. As a summarization, we
defined the commence date of any intervention
as the median date of different intervention
initiation dates if available and thus generated a
new variable named “any intervention.” This
simple “averaging method” provided a direct
way for us to inspect the effect of interventions
on
Rt.
We introduced a new counterfactual estimator
to infer causal relationships between
interventions and Rt using time-series cross-
sectional data (see Appendix Fig. 3 in
Supplemental Materials found at
https://doi.org/10.1016/j.jval.2021.10.007).
Counterfactual estimator compares the
observed outcomes with those one would
expect if the intervention had not been
implemented. In brief, the counterfactual
estimator first constructs a model using time-
series observations in the preintervention
period and then takes observations under
intervention as missing data and directly
estimates their counterfactuals. This method
has been detailed in previous articles and shown
to provide more reliable causal effects than the
conventional linear 2-way fixed effect models
when the intervention effect is heterogeneous
among units or there exist unobserved time-
varying confounders.23 Therefore, the improved
model was able to take account of the
influences of time factor and country (unit)
factor (such as population and Gross Domestic
Product) on outcomes.
The original article23 provided 3 sets of
counterfactual estimators and we chose the
improved interactive 2-way fixed-effects model
because of its ability to deal with time-varying
confounders, as suggested by the author.
 The model is as follows:
For any i = 1, 2, ., N and t = 1, 2, ., T,
Yit ¼ditDit1Xit b1l ift1ai1xt1εit
0 0
where Yit is the outcome (Rt) for country i at
time t; Dit is intervention indicator that equals 1
if country i is under intervention at time t and
equals 0 otherwise; dit is the intervention effect
on country i at time t; Xit is a (p31) vector of
exogenous covariates; b is a (p31) vector of
unknown parameters; ft is an (r 3 1) vector of
unobserved common factors; and li is an (r 3 1)
vector of unknown factor loadings. Intuitively,
factors can be understood as time-varying
trends that affect each country differently, and
factor loadings capture their heterogeneous
impacts caused by each country’s various
unobserved characteristics. Here, the interactive
component l ift implicitly captures the effects of
0
unobserved timevarying confounders and the
effects of other policies, through which the
influence of other policies is eliminated or
controlled when performing estimations of dit. ai
and xt are additive country and time fixed
effects, respectively, and εit represents
unobserved idiosyncratic shocks for country i at
time t and has 0 mean.
The primary causal quantity of interest is the
average intervention effect, which is an
approximation of the estimated effects of the
intervention on the outcome after policy
implementation over time. Details about the
calculation of average intervention effect were
shown in Appendix Method 1 in Supplemental
Materials found at
https://doi.org/10.1016/j.jval.2021.10.007.
Results
Overall, time-series data of the intervention
policies were retrieved for 178 countries on July
1, 2020, from the Oxford COVID-19 Government
Response Tracker. After exclusion, a total of 145
countries were included in the current study.
The number of countries in different continents
is as follows: 36 in Europe, 36 in Asia, 47 in
Africa, 13 in North America, 11 in South
America, and 2 in Oceania. Cumulative
infections per million population on July 1
ranges from 46 (Burundi) to 212154 (Peru), with
a median value of 9867 (interquartile range
2655-30581).
Association of Intervention Start-Date With Cumulative
Infections Per Million Population
Correlations between the Start-Date of 8
interventions and cumulative infections per
million population are shown in Table 1. Start-
Dates of all 8 interventions were significantly
and positively associated with the outcome,
suggesting that the later intervention was
commenced, the more infected cases that
would be expected in that country. Start-Dates
of public events cancellation (correlation
coefficient [r] = 0.45), school closing (r = 0.43),
and international travel controls (r = 0.43)
showed the most pronounced associations. We
displayed the boxplots of the outcome by
tertiles of Start-Date in Figure 1.
The distributions of cumulative infections by
tertitles of StartDate for 8 interventions are
presented in Figure 1. A similar monotonic
increasing trend of cumulative infections along
with Start-Date tertiles was observed for all
interventions. Countries in tertile 3
demonstrated notably more infections and
wider distributions than those in tertiles 1 and
2.
Additional partial correlation analysis that was
adjusted for the absolute date of first case
occurrence did not change the results
substantially (see Appendix Table 1 in
Supplemental Materials found at
https://doi.org/10.1016/j.jval.2021.10.007).
Sensitivity analysis by changing the definition of
Start-Date variable to days relative to the first
10 cases occurrence showed that the positive
associations still persist in most cases, although
some are not significant (see Appendix Table 2
in Supplemental Materials found at
https://doi.org/10.1016/j.jval.2021.10.007).
Association of Intervention Stringency and Duration With found at
Cumulative Infections Per Million Population
https://doi.org/10.1016/j.jval.2021.10.007).
The associations of intervention Stringency and
Duration with cumulative infections per million The results suggested some evidence that the
population at different epidemic phases are longer and stricter implementations of some

Table 1. Correlations of the Start-Date for 8 interventions with cumulative infections per million population on
July 1, 2020.

Interventions Correlation coefficients 95% CI

School closing 0.43 0.28-0.55

Workplace closing 0.28 0.12-0.42

Public events cancellation 0.45 0.31-0.57

Restrictions on gatherings 0.32 0.17-0.46

Public transport closing 0.22 0.06-0.37

Stay at home requirements 0.27 0.12-0.42

Restrictions on internal movement 0.27 0.12-0.42

International travel controls 0.43 0.29-0.55

Note. The correlation coefficients were calculated using Spearman rank correlation analysis. Start-Date for each intervention was the days of intervention initiation relative to the date of
first cumulative 100 cases occurrence.
CI indicates confidence interval.

presented in Table 2 and Appendix Table 3 in interventions in the very early phase but not the
Supplemental Materials found at middle phase were associated with reductions
https://doi.org/10.1016/j.jval.2021.10. 007. in infected cases at the end.
Most of the Stringency and Duration variables
Rt Before and After the Interventions
for the 8 interventions in the early phase (slow
growth period) were negatively correlated with The COVID-19 Rt before and after the
the outcome, with some of them showing implementation of 8 interventions is presented
significance (Table 2). Nevertheless, during the in Figure 2. Overall, a consistent similar pattern
middle phase (the fast growth phase), the was observed for all interventions that Rt
Stringency and Duration were mostly positively decreased slowly before the intervention, yet
correlated with the outcome. The average after the intervention, Rt decreased rapidly in 7
duration of the early phase for all countries was to 14 days, and the decreasing trend attenuated
61 days. We conducted a further analysis by afterward. Rt converged to around 1 in
calculating Stringency and Duration in the first approximately 30 days after the intervention.
month and the second month of the epidemic, Overall, the average Rt decreased by 6.7% (95%
respectively. Similar results were found that the CI 4.8-12.4) at 7 days and by 17.0% (95% CI 7.8-
Stringency and Duration variables in the first 29.1) at 14 days after any of the interventions
month were mostly negatively, whereas in the (see Appendix Fig. 4 in Supplemental
second month were mostly positively,
Materials found at
associated with cumulative infections (see
https://doi.org/10.1016/j.jval.2021.10.007).
Appendix Table 3 in Supplemental Materials
Counterfactual Estimates for the Effects of Interventions 2020) or later (August 1, 2020). The results
on Rt
demonstrate that the abovementioned findings
With counterfactual estimators, the average are roughly unchanged, although the estimates
effects of different interventions by the time are differ to some extent.
presented in Figure 3, and the average values
for all periods after intervention are presented Discussion
in Table 3. All interventions give average
In this study, we found some evidence that
estimates significantly , 0, among which the
earlier implementation, longer durations, and
estimate of international travel controls is
more strictness of containment policies at the
marginally significant. The test for no pretrend
early stage but not middle stage were
results is shown in Appendix Figure 5 in
associated with reduced infections of COVID-19.
Supplemental Materials found at https://doi.
With a novel counterfactual estimator, we were
org/10.1016/j.jval.2021.10.007. All 8
able to control for the unobserved timevarying
interventions have passed the equivalence test,
confounders, generating more reliable causal
suggesting the model successfully controlled for
relationships. Our results showed that the
the effects of time-varying confounders and
government intervention policies were
other interventions. In most cases, the average
associated with a 22% to 41% reduction in
effect estimates surround zero in the
COVID-19 transmission in approximately 25 to
preintervention period and decrease rapidly to
32 days after their implementations.
below zero in 7 to 14 days after the
intervention, to its minimum values (ranging Comparison With Previous Studies
from 20.52 to 20.08 with a median of 20.30) in The findings from our work align with those
25 to 32 days (Fig. 3). This corresponds to a from previous
maximum 22% to 41% reduction in Rt. Among studies, 8-13,15,24-28
except that previous results
the 8 interventions, school closing, workplace mostly depended on modeling assumptions
closing, and public events cancellation under presumptive scenarios or used data
demonstrated the strongest and most within a single country. Only a few studies
consistent evidence of associations. assessed the impact of intervention policies for
Robustness Analyses by Altering the Endpoint Date different countries using comparative
methods.14,15,26 Nevertheless, these studies
Appendix Tables 4 to 7 in Supplemental
mainly depended on straightforward statistical
Materials found at
methods, simply relating intervention policies to
https://doi.org/10.1016/j.jval.2021.10.007
COVID-19 growth rate or Rt directly, which failed
provide the robustness analyses for correlation
to account for time-varying confounders that
results between variables of interventions and
affected the effect estimates. One study
cumulative infections, and Appendix Tables 8
comparing the COVID-19 curve trends before
and 9 in Supplemental Materials found at
and after interventions using data from 54
https://doi.org/10.1016/j.jval.2021.10. 007
countries suggested that stay at home orders,
provide the robustness analyses for
curfews, and lockdowns curbed the increase in
counterfactual effect estimates on Rt, by
daily new case to , 5% within a month.26 Another
altering the cutoff date 1 month earlier (June 1,

Figure 1. Association between Start-Date for 8 interventions and cumulative infections per million
population on July 1, 2020, using boxplots. The figure shows boxplots of cumulative infections per
million population by tertiles of Start-Date for each intervention using paired data from 145
countries. The boxes show the quartiles of the cumulative infections per million population. The
whiskers extend to show the rest of the distribution, and the points are outliers.
Table 2. Correlations of the Stringency and Duration for 8 interventions with cumulative infections per
million population on July 1, 2020.

Interventi Stringency Duration

ons
 Correlation coefficient 95% CI Correlation coefficient 95% CI
Early phase

School closing 20.14 20.30 to 0.02 20.15 20.31 to 0.01

Workplace 20.05 20.11 to 0.21 20.02 20.18 to 0.15

closing

Public events 20.16 20.31 to 0.00 20.18 20.33 to 20.02

cancellation

Restrictions on 20.02 20.18 to 0.14 20.10 20.26 to 0.06

gatherings

Public transport 0.04 20.13 to 0.20 0.04 20.13 to 0.20

closing
Stay at home requirements 20.05 20.12 to 0.21 20.01 20.18 to 0.15
Restrictions on internal movement 20.03 20.14 to 0.19 20.02 20.14 to 0.18

International travel controls 20.18 20.33 to 20.02 20.23 20.38 to 20.07

Middle phase

School closing 0.11 20.07 to 0.27 0.17 0.00-0.34

Workplace closing 0.34 0.17-0.48 0.34 0.18-0.48

Public events cancellation 0.15 20.02 to 0.31 0.15 20.02 to 0.32

Restrictions on gatherings 0.34 0.18-0.48 0.22 0.05-0.38

Public transport closing 0.15 20.02 to 0.32 0.25 0.08-0.41

Stay at home requirements 0.18 0.01-0.34 0.24 0.07-0.39

Restrictions on internal movement 0.26 0.10-0.42 0.33 0.17-0.47

International travel controls 20.03 20.20 to 0.15 0.03 20.15 to 0.20

Note. The correlation coefficients were calculated using Spearman correlation analysis, separately in the early phase and middle phase. CI indicates
confidence interval.

study including 149 countries leveraged a simple results from our study provided more reliable
meta-analysis method and synthesized the evidence and could better assist policy making.
incidence rate ratios of COVID-19 before and
after the implementation of physical distancing, Interpretation of Our Findings
concluding that physical distancing was We found that the early implementation of all
associated with a 13% reduction in COVID-19 containment policies was associated with
incidence.15 This study had less focus on the reduced infection cases. This finding was as
timeliness, strictness, and durations of expected and in concert with most previous
interventions and was thus not able to conclude studies.13,29-31 Alongside this finding, we also
causal relationships. To the best of our found some evidence that the higher stringency
knowledge, our study is the first study that and longer duration of some containment
addressed the issue of confounding using a policies at the early or slow growth stage were
novel counterfactual estimator based on an correlated with reduced infection cases.
interactive 2-way fixed-effects model. The Nevertheless, results from the middle or fast
growth stage suggested evidence of positive
associations. This is a novel finding that previous
studies did not address. The positive
associations between Stringency and Duration
of intervention in the middle stage and total
infections were probably attributed to reverse
causality, which means that some countries
strengthened and prolonged the interventions
in face of more severe situations.
Recently, the new variants of severe acute
respiratory syndrome coronavirus 2, especially
the Delta variant that is more contagious than
the original strain, spread rapidly in some
countries such as India and the United States.
Evidence regarding whether government
intervention policies are effective on containing
the new variants is scarce because most
countries have loosened restrictions on public
activities. Nevertheless, a recent regional
outbreak of the Delta variant attacked
Guangzhou and Shenzhen in China from May
2021 to June 2021. The local governments
immediately enforced strict control measures
since the identification of the first new case,
including public events cancellation,
unnecessary workplace closing, and contact
tracing. The regional outbreak was successfully
controlled within a month, preventing virus
spillover and large-scale spreading.32 On the
contrary, countries that did not implement strict
containment measures at the very beginning are
experiencing an uncontrollable domestic
outbreak.33 This provides us some preliminary
evidence that the early and stringent
interventions are effective in controlling the
outbreak of new variants. Given the strong
transmissibility of the new variants,
governments should enforce aggressive control
measures as early as possible, even though the
growth rate might be very slow in their
countries at the early period. It seems too late
to remedy when arriving at the fast growth
stage.
The descriptive results from Figure 2 show that
Rt demonstrated a decreasing trend before the
intervention, which suggested that apart from
the 8 interventions, some other unobserved
factors such as public self-protective measures
also had an effect on transmission reduction.
Nevertheless, the preintervention period
decreasing trend disappeared in Figure 3 with
our counterfactual estimator, suggesting that
our methods had successfully eliminated the
effects of unobserved confounding factors and
generated less biased effect estimates. Notably,
we observed the

Figure 2. COVID-19 Rt before and after the implementation of 8 interventions. The black lines show the
mean value of Rt on different days relative to the start of intervention implementation. The shaded
areas show corresponding 95% confidence intervals of R t. The horizontal green lines indicate R t equal
to 1, and vertical green lines indicate the start of intervention implementation.
Rt indicates time-varying reproduction number.

Figure 3. Counterfactual estimates for the effects of 8 interventions on R t. The curves and surrounding
shaded areas show the average intervention effect estimates (with corresponding 95% confidence
intervals) on Rt by time. The bar plots at the bottom indicate the number of countries under the
related policy for each time period. The horizontal axes show the days relative to intervention, and
numbers , 0 indicate the preintervention periods.
Rt indicates time-varying reproduction number.

Table 3. Counterfactual estimates for the average effects of 8 interventions on R t.

Intervention AIE on Rt 95% CI P value

School closing 20.29 20.40 to 20.19 5.28E-08

Workplace closing 20.29 20.38 to 20.20 5.28E-11

 Public events cancellation 20.39 20.52 to 20.27 7.12E-10

Restrictions on gatherings 20.24 20.35 to 20.14 7.63E-06

Public transport closing 20.11 20.20 to 20.03 3.55E-03

Stay at home requirements 20.17 20.25 to 20.08 1.02E-04

Restrictions on internal movement 20.21 20.28 to 20.14 7.58E-09

International travel controls 20.20 20.39 to 20.02 3.16E-02

Note. The data show the average effects of intervention policies on R t for all countries and across postintervention periods. AIE indicates
average intervention effect; CI, confidence interval.
strongest and consistent effects for school closing, workplace closing, and public events cancellation.
All 3 containment policies were mandatory policies and more likely to take effects because it is
easier to close public facilities.

Quantitatively, we found most interventions took their effects on reducing Rt rapidly about 7 to 14
days after implementation. The effects were strengthened by time to a maximum effect of around
30% reduction for Rt in 25 to 32 days. The estimates were similar to a previous study, 34 except that
our results provided the effect trends over time.

Limitations

Our study does have several limitations. First, the coding of intervention variables from Oxford
COVID-19 Government Response Tracker relied on government announcements. Nevertheless,
announcements did not guarantee mandatory implementation and people adherence varied
because of the cultural and legal system differences. Second, because of the relatively small sample
size for the number of countries, not all correlation analyses are significant, especially for Stringency
and Duration; hence, those findings need to be interpreted with caution. Third, in addition to the
public containment and closure policies, other personal protection strategies including wearing
masks, quarantine, and hand hygienealsoplayedanimportantrole inepidemicmitigation. Those
strategies were not the focus of our current study and have been addressed in previous
researches.4,5,35-37 Moreover, some interventionpolicies wereoftenintroducedinclose temporal
sequences. It has been difficult to untangle the individual effects. Although our counterfactual
approach proved to have been largely controlled for the effects of time-varying confounders and
other policies, statistical models dealing with confounders might be not perfect. Hence, results of
interventions that are temporally correlated need to be interpreted with caution. Fourth, a large
proportion of confirmed cases and deaths has been recorded from nursing homes including both
residents and careworkers.38 Nevertheless, data regarding the fraction of cases and deaths emerging
from nursinghomes were not available for most countries. We were not able to investigate the
effects of the general policy interventions on nursing home epidemics at this point.

Conclusions

Using epidemiological data from 145 countries, we found some evidence that earlier, stricter, and
longer implementation of containment policies at the early stage was associated with a reduction in
infected cases. Moreover, the novel counterfactual estimator proved to have generated more
reliable intervention effect estimates of policies. Our results provided evidence of the quantitative
effect of different policy intervention over time. Those findings shall have important implications for
governments to enact or lift containment policies in fighting against the current and future waves of
the COVID-19 outbreak. Future studies should emphasize on how adding and removing intervention
policies affect the transmission of the virus, especially its new mutants such as the Delta variant, for
decision making on lifting containment policies.

Supplemental Material
Supplementary data associated with this article can be found in the online version at https://doi.org/10.1016/j.jval.2021.10.007.

Article and Author Information

Accepted for Publication: October 5, 2021 Published Online: xxxx

doi: https://doi.org/10.1016/j.jval.2021.10.007
Author Affiliations: Jarvis Lab, Department of Medicine and Healthcare, Tencent Technology (Shenzhen) Company, Shenzhen, China (Sun, Zheng, Luo,
Alexander Ng); China State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of
Guangzhou Medical University, Guangzhou, China (Liang, Yang, Zeng, He, Zhong); Guangzhou Chest Hospital, Guangzhou, China (Li).

Correspondence: Jianxing He, PhD, China State Key Laboratory of Respiratory Disease and National Center for Respiratory Medicine, Guangzhou, China. Email:
hejx@vip.163.com
Man Tat Alexander Ng, MBChB, MPH, Department of Medicine and Healthcare, Tencent Technology (Shenzhen) Company, Shenzhen, China. Email:
alexanderng@tencent.com

Author Contributions: Concept and design: Sun, Zheng, Liang, Yang, Li,
Luo, He, Zhong
Acquisition of data: Sun, Luo
Analysis and interpretation of data: Sun, Zheng, Liang, Yang, Zeng, Li, Luo
Drafting of the manuscript: Sun, Zheng, Zeng, Luo
Critical revision of the paper for important intellectual content: Sun, Zheng,
Liang, Yang, Zeng, Li, Luo, Alexander Ng, He
Statistical analysis: Sun, Luo
Administrative, technical, or logistic support: Alexander Ng, Zhong Supervision: Alexander Ng, He, Zhong

Conflict of Interest Disclosures: The authors reported no conflicts of interest.

Funding/Support: This work was funded by Key-Area Research and Development Program of Guangdong Province, China (No. 2018B010111001).
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