Available via license: CC BY 4.0
Content may be subject to copyright.
1
HiroiS, etal. BMJ Open 2017;7:e015855. doi:10.1136/bmjopen-2017-015855
Open Access
ABSTRACT
Objectives To explore the prevalence of Helicobacter
pylori infection in Japan and the trends of its eradication
therapy before and after the changes of the insurance
coverage policy, rst started in 2000, and expanded to
cover H. pylori-positive gastritis in 2013. The impacts that
the changes brought were estimated.
Methods In this retrospective observational study and
simulation study based on health insurance claims data,
product sales data and relevant studies, individuals
who received triple therapy (amoxicillin, clarithromycin,
proton-pump inhibitors or potassium-competitive acid
blockers) were dened as the rst-time patients for H.
pylori eradication in two Japanese health insurance claims
databases (from approximately 1.6 million and 10.5 million
individuals). Each sales data of eradication packages and
examination kits were used to estimate the number of H.
pylori-eradicated individuals nationwide. The prevalence of
H. pylori infection, including the future rate, was predicted
using previous studies and the estimated population trend
by a national institute. Cases completed prior to the policy
change on insurance coverage were simulated to estimate
what would have happened had there been no change in
the policy.
Results The numbers of patients rst received eradication
therapy were 81 119 and 170 993 from two databases.
The nationwide estimated number of patients successfully
eradicated was approximately 650 000 per year between
2001 and 2012, whereas it rapidly rose to 1 380-000 per
year in 2013. The estimated prevalence of infection in
2050 is 5%, this rate was estimated to be 28% and 22%
if the policy changes had not occurred in 2000 and 2013,
respectively.
Conclusions The impact of policy changes for H. pylori
eradication therapy on the prevalence of infection was
shown. The results suggest that insurance coverage
expansion may also reduce the prevalence in other
countries with a high prevalence of H. pylori infection if the
reinfection is low.
INTRODUCTION
Throughout the world, gastric cancer is one
of the most common cancers; 952 000 new
patients were diagnosed in 2012.1 The inci-
dence of gastric cancer is higher in Asian
countries; Korea, Japan and China have the
first, third and fifth highest rates, respectively,
in the world.2 In Japan, the prevalence and
mortality of gastric cancer are constantly
among the top three of all cancers. There-
fore, it is considered to be one of the highest
priorities in preventive policy. Helicobacter
pylori can cause gastric inflammation, which
can then lead to gastric and duodenal ulcers,
as well as gastric cancer.3–5 Thus, eradica-
tion of H. pylori is considered as an effective
therapy in reducing the risk of those diseases.
Due to the concern of high gastric cancer
prevalence in East Asian countries, some
Impact of health insurance coverage for
Helicobacter pylori gastritis on the
trends in eradication therapy in Japan:
retrospective observational study and
simulation study based on real-
world data
Shinzo Hiroi,1,2 Kentaro Sugano,3 Shiro Tanaka,4 Koji Kawakami1
To cite: HiroiS, SuganoK,
TanakaS, etal. Impact of
health insurance coverage for
Helicobacter pylori gastritis
on the trends in eradication
therapy in Japan: retrospective
observational study and
simulation study based on
real-world data. BMJ Open
2017;7:e015855. doi:10.1136/
bmjopen-2017-015855
►Prepublication history and
additional material for this
paper are available online. To
view these les please visit the
journal online (http:// dx. doi.
org/ 10. 1136/ bmjopen- 2017-
015855).
Received 4 January 2017
Accepted 23 May 2017
1Department of
Pharmacoepidemiology,
Graduate School of Medicine
and Public Health, Kyoto
University, Kyoto, Japan
2Japan Medical Affairs, Takeda
Pharmaceutical Company
Limited, Tokyo, Japan
3Department of Medicine, Jichi
Medical University, Tochigi,
Japan
4Department of Clinical
Biostatistics, Graduate School
of Medicine, Kyoto University,
Kyoto, Japan
Correspondence to
Dr Koji Kawakami;
kawakami. koji. 4e@ kyoto- u.
ac. jp
Research
Strengths and limitations of this study
►Demonstrates for the rst time the impact of
insurance policy expansion for Helicobacter pylori
eradication therapy in a quantitative manner based
on an analysis ofnationwide real-world data.
►Robust and reliable results were obtained from
combinations of large-scale insurance claims
databases and sales data of the most commonly
usederadication treatments and test kits.
►The success rate of eradication was obtained
from previous studies; therefore,the rate might be
different from current clinical practice.
►The health insurance claims databases have
potential biases: in one database,the information on
individuals older than 65 years is limited because
it is theinformation from employed individuals and
their family members, whereas another database
included the data only from large hospitals.
group.bmj.com on August 1, 2017 - Published by http://bmjopen.bmj.com/Downloaded from
2HiroiS, etal. BMJ Open 2017;7:e015855. doi:10.1136/bmjopen-2017-015855
Open Access
preventive programmes have been launched to reduce
the incidence of gastric cancer. In Korea, a cancer
screening programme was established by the government
to provide for almost all people of eligible age (40 years or
older for gastric cancer) with free screening or provision
at minimum cost in 1999.6 Large clinical trials and health
economic studies have been conducted in China, and a
consensus statement was formulated to encourage H. pylori
eradication therapy.6 7 In Taiwan, the results of a commu-
nity-level large screening and eradication programme, as
well as a health economic evaluation, support the efficacy
of H. pylori eradication therapy.8 In Japan, in November
2000, based on the results of diverse clinical studies,3 9–20
the government approved the addition of H. pylori erad-
ication therapy in their insurance policy as a treatment
for H. pylori-positive gastric ulcer and duodenal ulcer.
Furthermore, insurance coverage was expanded in June
2010 to include gastric mucosa-associated lymphoid tissue
lymphoma, idiopathic thrombocytopenic purpura and
postendoscopic resection of early gastric cancer, and in
February 2013, to include H. pylori-positive gastritis based
on the recommendations of Japanese guideline.21
Japanese health insurance is a system of universal
coverage; the effect of change in health insurance
coverage policy is spread throughout the nation. In terms
of H. pylori eradication, anyone diagnosed with a disease
covered for eradication therapy by health insurance can
receive eradication therapy with coverage. Therefore,
health insurance reimbursement seems to have the same
or greater impact on clinical practice as recommenda-
tions from diagnostic/treatment guidelines in countries
where universal health insurance coverage is established,
such as in Japan and Korea. Various sizes of preventative
programmes for gastric cancer have been implemented
in the high prevalence countries for both gastric cancer
and H. pylori infection. In some countries, H. pylori erad-
ication therapy for patients with H. pylori-positive gastric
ulcer and duodenal ulcer has been covered by national
health insurance. However, eradication therapy for H.
pylori-positive gastritis has not been covered to date in
these countries other than Japan.8 The effect of insur-
ance coverage expansion on the prevalence of H. pylori
infection has been evaluated in only a few studies at the
community level in Japan.22 23 Nonetheless, the nation-
al-level prevalence rate of H. pylori infection has not
been reported and its change has not been assessed after
the insurance coverage for H. pylori eradication therapy
was expanded to include H. pylori-positive gastritis in
2013. The progressive insurance expansion was reported
to be efficient,24 and the incidence of peptic ulcer has
decreased since the change in insurance coverage policy
for H. pylori eradication in 2000.25 They also estimated
that gastric cancer mortality would decrease based on
the assumption that 50% of patients infected with H.
pylori would receive eradication therapy.26 However, this
estimate was based on neither the observed number of
patients undergoing H. pylori eradication nor the preva-
lence rate of infection. To evaluate the impact of changes
to the insurance policy on the incidence of various
diseases, including gastric cancer, it is necessary to eluci-
date the national trend of eradication therapy and the
prevalence rate of infection before and after the changes
in the insurance policy.
The primary objective of this study was to assess how
health insurance policy changes have impacted eradica-
tion therapy and the prevalence rate of H. pylori infection
in Japan. Furthermore, the future effect, as a result of the
policy changes, on the prevalence of H. pylori infection
was evaluated. In this study, health insurance claims data-
bases and product sales data were used to estimate the
number of eradication treatments. The successful eradi-
cation rate from 2000 onwards, at which time the health
insurance began its coverage for the eradication therapy,
was also estimated. The prevalence rate of infection
and the number of infected individuals up to 2060 were
predicted as based on the above data analysis and the prev-
alence rate of H. pylori infection as reported in previous
studies. Furthermore, a simulation was conducted to esti-
mate what the probable effects would be had the policy
changes not been made.
METHODS
Data sources
Insurance claims databases from Japan Medical Data
Center (JMDC) from January 2005 to December 2015
and Medical Data Vision (MDV) from April 2008 to
December 2015 were used for the analyses. The JMDC
database is a registry of health insurance claims and
medical examination records for insured individuals
and their families in more than 50 health insurance soci-
eties. Because this database only included information on
company employees and their families, the information
for those older than 65 years was limited. Also, there were
no data for those older than 75 years. Until 2014, this
database covered 1.6 million individuals which accounted
for 1% of the Japanese population. The medical database
from MDV covered 10.5 million individuals in 192 acute
care hospitals using diagnostic procedure combination/
per diem payment system (DPC/PDPS). It included 11%
of acute care hospitals in Japan with the number of beds
from 20 to more than 1000. These databases included the
patient’s gender, age, diagnosis, prescription information
and so on. Diagnosis information is based on the Interna-
tional Classification of Diseases, tenth revision, and drugs
are coded in the Anatomical Therapeutic Chemical Clas-
sification System. Both databases included anonymous
and personally unidentifiable data.
To estimate the nationwide number of infected individ-
uals, product sales data for the most common eradication
medicine and test kit for H. pylori infection were analysed.
The sales data for eradication medicine, Lansap (Takeda
Pharmaceutical), which consists of lansoprazole, amoxi-
cillin and clarithromycin in one package, was provided
by the manufacturer from December 2002 to December
2015. The data for 13C-urea breath test (UBIT, Otsuka
group.bmj.com on August 1, 2017 - Published by http://bmjopen.bmj.com/Downloaded from
3
HiroiS, etal. BMJ Open 2017;7:e015855. doi:10.1136/bmjopen-2017-015855
Open Access
Table 1 Studies on the number of Helicobacter pylori-infected individuals and prevalence rate of infection
First author No of subjects Population Study design
Observation
year
Asaka27 426 Asymptomatic children, students and adults
(participating at the health screening centre)
living in Sapporo, Hokkaido
Observational study 1990
Fujisawa31 349 Healthy persons living in seven prefectures in
the central part of Japan
Observational study 1974
324 1984
342 1994
Watabe32 6983 Participants in a mass health appraisal
programme
Observational study 1996
Ueda33 14 716 Individuals who underwent a health check-
up in seven prefectures (Hokkaido, Aomori,
Yamagata, Gunma, Aichi, Shiga and Kagawa)
Observational study 2005
Shiota34 5550 Patients of Oita University Hospital, Oita, Japan Observational study 2009
Pharmaceutical) from November 2000 to December
2015 were as well obtained.
To determine the trend in the number of H. pylori-in-
fected individuals, previously published Japanese studies
were used (table 1).
Study design
This study is a retrospective observational study and simu-
lation study based on the health insurance claims data,
product sales data and relevant published studies. The
steps were as follows: first, the number of individuals
who received the eradication therapy and those who had
successful eradication were estimated based on the anal-
yses of the health insurance claims databases and product
sales data; second, the trend in the number of H. pylo-
ri-infected individuals was determined from previously
published studies; third, the prevalence rate and trend
of H. pylori infection were estimated and forecasted from
the results of the first and second step. Finally, to fully
evaluate the impact of the policy changes, a simulation
was made considering effects which likely would have
occurred without the insurance policy changes in 2000
and 2013.
Patient identication and analysis
In the JMDC and MDV databases, the individuals who
received triple therapy, either the primary eradication
package (such as Lansap and other packaged products)
or the combination of amoxicillin, clarithromycin and
either proton-pump inhibitors or potassium-competi-
tive acid blockers (P-CABs) (all prescribed within the
same month), were defined as individuals with primary
eradication of H. pylori. The drugs used for the therapy
were defined by product name in JMDC database and
remuneration code in MDV database. The examination
was defined by remuneration code, and the diagnosis
for those who had eradicated was defined by name of
diagnosis in both databases. To estimate the number of
individuals who received primary eradication therapy in
the nation, the following were calculated in these data-
bases:
1. Percentage of individuals who used Lansap for
primary eradication therapy to all individuals who
received the primary eradication.
2. Percentage of individuals who received UBIT for the
H. pylori test after eradication to all individuals who
took the H. pylori test.
To calculate the number of individuals who achieved
successful eradication, the following were assumed
(figure 1):
►The primary and secondary success rates of
eradication for this study were presumed to be 75%
and 90%, respectively, based on previous studies
in Japan.25 27 Secondary eradication was premised
to be performed for all those who failed primary
eradication. Therefore, the success rate of the
eradications was estimated to be 98% of the primary
eradication, and the percentage was used as the
success rate in this study.
►New infection in adulthood was reported to be rare28
and reinfection per year after the eradication therapy
in Japan is reported to be approximately 1%29 30;
however, it was assumed to be 0% in this study.
The nationwide number of individuals who received
primary eradication was estimated based on the above
points 1. and 2. with sales data of Lansap and UBIT as
follows:
►The monthly number of individuals who received
primary eradication from January 2010 was calculated
as the mean of four estimates (Lansap-base from MDV
and JMDV, and UBIT-base from MDV and JMDC).
►The monthly number of individuals who received
primary eradication from January 2006 to December
2009 was calculated as the mean of two estimates from
the JMDC database (Lansap-base and UBIT-base).
►The monthly number of individuals who received
primary eradication from November 2000 to
December 2005 was extrapolated using the sales
number of UBIT in each month and the UBIT share
group.bmj.com on August 1, 2017 - Published by http://bmjopen.bmj.com/Downloaded from
4HiroiS, etal. BMJ Open 2017;7:e015855. doi:10.1136/bmjopen-2017-015855
Open Access
Figure 1 The model used to calculate the number of individuals with successful Helicobacter pylori eradication.
rate in 2006 on the assumption that the share rate in
this period was the same as that in 2006.
The formulae used are as follows:
►(Successful eradication number)YM = (Primary
successful eradication number)YM + (Secondary
successful eradication number)YM
►(Primary successful eradication number)YM = (Primary
eradication number)YM × (Primary eradication success
rate, 75%)
►(Secondary successful eradication number)YM=
((Primary eradication number)YM − (Primary
successful eradication number)YM) × (Secondary
eradication success rate, 90%)
►(Primary eradication number)YM = ((Primary
eradication number with Lansap)YM,JMDC + (Primary
eradication number with Lansap)YM,MDV + (Primary
eradication number with UBIT)YM,JMDC + (Primary
eradication number with UBIT)YM,MDV)/4
►(Primary eradication number with Lansap)YM,database =
(Sales number of Lansap)YM / (Share of Lansap)YM,database
►(Primary eradication number with UBIT)YM,database =
(Examination number)YM,database × (Ratio of primary
eradication to total examination)YM,database
►(Examination number)YM,database = (Sales number of
UBIT)YM / (Share of UBIT)YM,database where YM is year
month and database = JMDC or MDV database.
The number of infected individuals and prevalence rate
of infection were estimated based on the previous Japa-
nese studies shown in table 1. The number of infected
individuals until March 2013 was estimated from previous
studies27 31–34 and vital statistics in Japan conducted by
Ministry of Health, Labour and Welfare.35 An exponen-
tial decay approximation curve was calculated based on
the results of the previous studies until 2000. After 2000,
the estimated mean monthly number of individuals
who achieved successful eradication from January 2001
to March 2013 was taken into account. The number of
infected individuals from April 2013 was estimated using
the estimated mean monthly number of individuals
who achieved successful eradication from April 2013 to
December 2015, giving consideration to the decrease in
the number of infected individuals due to death. It was
calculated as follows:
(Infection number)
CY
=∑
DOBYRNational PopulationDOBYR, CY ×Prevalence RateDOBYR, CY
∑DOBYRNational PopulationDOBYR, CY
where (Prevalence rate)DOBYR,CY is the prevalence rate of
H. pylori infection by birth year in each observation year
calculated in this study, and (National population)DOBYR,CY
is the population by birth year in each observation year,
where DOBYR is birth year by 5 years and CY is the
calendar year of observation of each study. An expo-
nential parameter that minimises the sum of squared
distances from (Infection number)CY was calculated (least
squares method), assuming the decrease of the number
of H. pylori infected individuals by any reason other than
eradication (ie, ageing) followed an exponential function
and the decrease of that by eradication was constant from
2001 to 2013.
Assuming that H. pylori infection would be decreasing
exponentially after 2015 (by consideration of the natural
decrease due to the death of older infected individuals),
a simulation was performed using the number of infected
individuals obtained in the previous section and the popu-
lation forecast from the National Institute of Population
and Social Security Research36 to predict the number of
group.bmj.com on August 1, 2017 - Published by http://bmjopen.bmj.com/Downloaded from
5
HiroiS, etal. BMJ Open 2017;7:e015855. doi:10.1136/bmjopen-2017-015855
Open Access
infected individuals in the future. The prevalence rate
of infection was also simulated for the case of no policy
change regarding insurance coverage in 2000 and 2013.
This was simulated as follows:
1. The number of H. pylori-infected individuals calculated
in the previous section was taken to be (Infection
number)CY before 2013.
2. The number of H. pylori-infected individuals from
2013 to 2015 was assumed to be decreased from
(Infection number)CY before 2013, based on the
estimated number of individuals who achieved
successful eradication by the analysis of the JMDC and
MDV databases and sales data of drugs.
3. If case 0, (Prevalence rate)CY,case = (Infection number)CY
/ (National population)CY, in 1975≤CY≤2015 or
(Prevalence rate)CY,case / (Prevalence rate)CY-1,case =
(Prevalence rate)CY−1,case / (Prevalence rate)CY−2,case, in
2016≤CY.
4. If case 1, (Prevalence rate)CY,case = (Infection number)CY
/ (National population)CY, in 1975≤CY≤2000 or
(Prevalence rate)CY,case / (Prevalence rate)CY-1,case =
(Prevalence rate)CY−1,case / (Prevalence rate)CY−2,case, in
2001≤CY.
5. If case 2, (Prevalence rate)CY,case = (Infection number)CY
/ (National population)CY, in 1975≤CY≤2012 or
(Prevalence rate)CY,case / (Prevalence rate)CY−1,case =
(Prevalence rate)CY−1,case / (Prevalence rate)CY−2,case, in
2013≤CY.
Case 0 is with the current policy; case 1 or case 2 represents
the case in which policy change had not occurred in 2000
or 2013.
Statistical analysis was carried out using Excel 2010
(Microsoft) and SAS V.9.4 (SAS Institute).
RESULTS
Patient characteristics
The total number of individuals who received primary
eradication was 81 119 (mean age 36.8 years, males 61%)
from the JMDC database and 1 70 993 (mean age 60.6
years, males 57%) from the MDV database. The charac-
teristics for each year are shown in online supplementary
appendix, table S1.).
Trend in the number of individuals with the primary
eradication therapy and successful eradication
The difference among the four (Lansap-base from MDV
and JMDV, and UBIT-base from MDV and JMDC) esti-
mated numbers of individuals who received primary
eradication was confirmed to be minimal after 2010 (see
online supplementary appendix, figure S1). The nation-
wide number of individuals who had successful eradication
(both first line and second line) was estimated as shown
in figure 2. The number was approximately 650 000 per
year between 2001 and 2012, which has reached a steady
state of approximately 700 000 per year after an increase
in 2006. However, there was a slight decrease in 2011. It
markedly increased to 1 380 000 in 2013, which is more
than double the number observed in 2012. In the diag-
noses for those who had successful eradication treatment
(figure 2), gastritis accounted for more than half of the
diagnoses since 2013. The average number of individ-
uals who received successful eradication treatment up to
March 2013 was 54 000 per month, whereas it was 124 000
per month after March 2013. The cumulative total of
individuals who received successful eradication treatment
was more than 10 million up to September 2014.
Trend in the number of infected individuals and the prevalence
rate of infection
Figure 3A illustrates the prevalence rate of H. pylori infec-
tion by birth year from previous studies. This shows higher
prevalence rates of infection in the cohorts with earlier
birth years. Also, there was a tendency for the difference
of prevalence rates of infection among studies to be
larger in those with an earlier birth year, and the rate was
lower in later observations. The overall estimated preva-
lence rate of infection was lower in later years (figure 3B).
The lines were fitted after taking the effect of insurance
policy change in November 2011 into account, shown in
figure 3B.
Trend and prediction of H. pylori infection and the effect of
insurance policy changes
The pattern of the number of infected individuals from
2016 in Japan was predicted (blue broken line in figure 4)
based on the trend in the number of infected individuals
derived from the results above and the population fore-
cast.35 The patterns, in the case without policy changes in
insurance coverage in 2000 and 2013, were also simulated
(red and green broken lines in figure 4). The simulation
showed that the number of infected individuals would
decrease to 16 200 000 individuals in 2030, or 14% of the
population, and further decrease to 5% of the population
in 2050. These figures would have been 28% and 21% in
2030 if the policy changes had not occurred in 2000 and
2013, respectively.
DISCUSSION
This study described the status of eradication therapy and
trend of H. pylori infection using large insurance claims
databases that reflected actual clinical practice at the
national level in Japan. The analysis showed that the prev-
alence rate of H. pylori infection has decreased after the
approval to include eradication therapy in the insurance
policy in 2000. The number of successful eradications
more than doubled immediately after insurance coverage
for H. pylori eradication therapy was expanded in 2013.
The simulation indicated that the prevalence rate of H.
pylori infection would decrease and reach approximately
14% in 2030 and 5.4% in 2050.
Although it is difficult to compare the prevalence rate
of infection among studies due to time and sample differ-
ence, it is worthwhile to compare the rate with other
countries. The prevalence rate of H. pylori infection varies
markedly in different countries; in general, it is higher in
group.bmj.com on August 1, 2017 - Published by http://bmjopen.bmj.com/Downloaded from
6HiroiS, etal. BMJ Open 2017;7:e015855. doi:10.1136/bmjopen-2017-015855
Open Access
Figure 2 Annual number of individuals who had successful Helicobacterpylori eradication (both rstline and secondline).
*Others: gastric mucosa associated lymphoid tissue lymphoma, idiopathic thrombocytopenic purpura and postendoscopic
resection of early gastric cancer.
developing countries and lower in developed countries.37
The prevalence rate of infection was reported to be 92%
in Bangladesh,38 75% in Vietnam,39 41%–72% in China40
and 54%–60% in Korea,41 42 whereas it was 15%–22% in
Australia43 44 and 8%–27% in the USA.45 46 Although the
estimate of the prevalence rate of H. pylori infection in
our study was 43% in Japan in 2000, based on our simu-
lation, the prevalence rate of infection in Japan in 2030
with expanded insurance coverage would be almost the
same as the Australian rate (15%) and it would reach the
North American level (8%–27%) by approximately 2050.
The estimate from the previous studies indicated a
higher prevalence rate of infection in older cohorts,
which can be explained by environmental factors like
poor sanitation.47 48 It has also been suggested that nowa-
days H. pylori infection occurs in childhood in Japan.49 50
As a result, the number of infections would have naturally
decreased even without eradication therapy due to the
death of older infected individuals. However, our simula-
tion showed that the prevalence rate of infection would
have been higher than 14% and 7% in 2030 if the policy
changes had not occurred in 2000 and 2013, respec-
tively. It was, therefore, evident that those insurance
policy changes had contributed to the reduction in the
prevalence of H. pylori infection. Japan has established a
universal health insurance coverage system, which means
that by law all Japanese residents are entitled to health
insurance coverage for medical treatments. This system
has a great impact on the dissemination of medical treat-
ments; consequently, the use of eradication therapy is
highly influenced by the presence of the health insurance
and coverage for diseases.
The results of this study could be a good indicator for
the implementation of insurance coverage for eradica-
tion of H. pylori in countries where H. pylori is prevalent,
especially the East Asian countries. Countries and regions,
such as Korea, China and Taiwan, have been conducting
clinical trials of H. pylori eradication; however, they have
not yet established any policy for H. pylori eradication.
This study is likely to be used as one of the references
in considering effect on policy change in such countries.
This study might also be important in providing direction
for future research in Japan. In 2016, the revised edition
of the Japanese Guideline for Diagnosis and Treatment
for H. pylori Infection was published following that of
2009. In the latest guideline, the expansion of insur-
ance coverage for the treatment for H. pylori gastritis in
2013 is described.51 Also, a regimen with P-CAB-based
group.bmj.com on August 1, 2017 - Published by http://bmjopen.bmj.com/Downloaded from
7
HiroiS, etal. BMJ Open 2017;7:e015855. doi:10.1136/bmjopen-2017-015855
Open Access
Figure 3 Trends in (A) the percentages of Helicobacter pylori infection by birth year based on previous studies and (B) the
nationwide number of infected individuals as estimated based on the previous studies. *Data from the study by Watabe et al32
were excluded in (A) as that study divided the age group into two age groups: below and above age 60years.
group.bmj.com on August 1, 2017 - Published by http://bmjopen.bmj.com/Downloaded from
8HiroiS, etal. BMJ Open 2017;7:e015855. doi:10.1136/bmjopen-2017-015855
Open Access
Figure 4 Trend and prediction of the number of Helicobacter pylori-infected individuals. *Case 0, in current policy; †case 1, if
policy change had not occurred in 2000; ‡case 2, if policy change had not occurred in 2013.
triple therapy, which is newly described in the guideline,
demonstrated a high eradication rate compared with
the conventional proton-pump inhibitor-based triple
therapy.51 52 It seems that the prevalence rate of infection
could be further reduced in Japan.
Comparison with other studies
There have been some community-level studies inves-
tigating the status of eradication in clinical practices in
Japan.22 23 Nevertheless, to our knowledge, there was no
study describing the status of eradication therapy at the
national level. Asaka et al have reported that the insurance
policy change could increase the number of eradications,
reduce the number of infected individuals and decrease
mortality from gastric cancer.24 25 They estimated that
the number of deaths from gastric cancer would reach
60 000 in 2020 without any countermeasures, whereas
it would be half if 50% of infected individuals receive
eradication therapy. However, this assumption was not
based on actual observations. Our study, using real-world
data reflecting actual medical practice, showed a rapid
increase in patients receiving H. pylori eradication, after
the insurance policy change in 2013.
Strengths and limitations of this study
Here, a national-level evaluation using real-world data,
allowed us to analyse the impact of insurance policy
expansion for H. pylori eradication therapy in a quan-
titative manner. Furthermore, robust and reliable
results were obtained from combinations of large-scale
insurance claims databases and sales data of the most
commonly used eradication treatments and test kits.
However, this study has several limitations. First, the
success rate of eradication was obtained from previous
studies25 27; thus, the rate might be different from clin-
ical practice, including the possibility that it may be
estimated higher than the actual rate considering the
effect of the increase in bacteria resistant to antibiotics.
Nevertheless, the success rate in this study is believed to
be close to the actual rate. Second, the health insurance
claims databases have potential biases. The information
available was limited for those older than 65 years in
the JMDC database because it consisted of information
on employed individuals and their family members. In
addition, those who were self-employed and employees
in small-to-medium sized enterprises were not included.
group.bmj.com on August 1, 2017 - Published by http://bmjopen.bmj.com/Downloaded from
9
HiroiS, etal. BMJ Open 2017;7:e015855. doi:10.1136/bmjopen-2017-015855
Open Access
The information in the MDV database was obtained from
the hospital using DPC/PDPS. Indeed, the mean ages
of individuals who received primary eradication in both
databases were different. However, the product share
rates calculated in both databases were very similar after
2010, and the estimates of the number of individuals
with the primary eradication were almost identical in
both databases. Therefore, the impact of the different
age distribution was believed to be minimal, and the
estimates are believed to be accurate.
Despite these limitations, this study used the informa-
tion from reliable clinical studies and large databases
covering a significant number of Japanese citizens.
Consequently, it is believed that the information
presented here reflects the clinical status in Japan.
Conclusion and policy implications
This study described and forecasted the trend of H. pylori
eradication therapy and assessed the impact of insur-
ance policy change on the prevalence rate of H. pylori
infection. It has demonstrated that the policy change
was associated with a reduction in the prevalence rate of
H. pylori infection in Japan. Furthermore, it is expected
to lead to a reduction in the incidence of gastric cancer.
Adaptation of a similar nationwide health insurance
coverage plan for H. pylori eradication by other high
risk countries and regions may reduce the prevalence of
H. pylori infection in the short and medium terms and
may also have the possibility to have a positive effect on
the incidence of H. pylori-related conditions, including
gastric cancer, in the future.
Acknowledgements The authors thank Takeda’s collaborator, Otsuka
Pharmaceutical, for providing sales data of urea breath test diagnostic kits (UBIT).
The authors thank Kosuke Iwasaki and Tomomi Takeshima, employees of Milliman,
for analysing the database, and writing and editorial support, respectively, funded
by Takeda Pharmaceutical.
Contributors SH, KS and KK contributed to the concept and design of the study.
SH contributed to acquisition of data. SH contributed to the analysis. SH, KS and ST
contributed to interpretation of data. SH, KS, ST and KK contributed to the writing of
the manuscript and critical revision of the manuscript. All authors approved the nal
version of the manuscript. KK is the guarantor of the article.
Funding This study was sponsored by Takeda Pharmaceutical.
Competing interests SH is an employee of Takeda Pharmaceutical. KS received
research grants from Eisai, Daiichi Sankyo Pharma and Takeda Pharmaceutical.
He also received lecture fees from Astellas Pharma, Fujilm and Takeda
Pharmaceutical. ST has no personal interests to declare. KK received research
funds from Dainippon Sumitomo Pharma, Olympus, Stella Pharma, Medical
Platform, Novartis Pharmaceutical, Bayer and Maruho; honorarium from Astellas,
Daiichi Sankyo Pharma, Taisho Pharmaceutical, Eisai, Novartis Pharmaceutical,
Mitsubishi Tanabe Pharma, Takeda Pharmaceutical and Sano; consulting fees from
Olympus, Kyowa Hakko Kirin, Kaken Pharmaceutical and Otsuka Pharmaceutical.
There are no patents, products in development or marketed products to declare,
relevant to those companies.
Patient consent Detail has been removed from this case description/these case
descriptions to ensure anonymity. The editors and reviewers have seen the detailed
information available and are satised that the information backs up the case the
authors are making.
Ethics approval This study was approved by Ethic Committee, Kyoto University
Graduate School and Faculty of Medicine (R0126-1). This study was exempted from
obtaining individual informed consent based on Ethical Guidelines for Medical and
Health Research Involving Human Subjects by Ministry of Education, Culture, Sports,
Science and Technology, and Ministry of Health, Labour and Welfare.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.
Open Access This is an Open Access article distributed in accordance with the
terms of the Creative Commons Attribution (CC BY 4.0) license, which permits
others to distribute, remix, adapt and build upon this work, for commercial use,
provided the original work is properly cited. See: http:// creativecommons. org/
licenses/ by/ 4. 0/
© Article author(s) (or their employer(s) unless otherwise stated in the text of the
article) 2017. All rights reserved. No commercial use is permitted unless otherwise
expressly granted.
REFERENCES
1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and
mortality worldwide: sources, methods and major patterns in
GLOBOCAN 2012. Int J Cancer 2015;136:E359–E386.
2. World Cancer research Fund International. Stomach cancer
statistics, 2016. http://www. wcrf. org/ int/ cancer- facts- gures/ data-
specic- cancers/ stomach- cancer- statistics.
3. Fukase K, Kato M, Kikuchi S, et al. Japan Gast Study Group. Effect
of eradication of Helicobacter pylori on incidence of metachronous
gastric carcinoma after endoscopic resection of early gastric cancer:
an open-label, randomised controlled trial. Lancet 2008;372:392–7.
4. Marshall BJ, Armstrong JA, McGechie DB, et al. Attempt to
full Koch's postulates for pyloric Campylobacter. Med J Aust
1985;142:436–9.
5. Morris A, Nicholson G. Ingestion of Campylobacter pyloridis
causes gastritis and raised fasting gastric pH. Am J Gastroenterol
1987;82:192–9.
6. IARC Working Group. Helicobacter pylori eradication as a strategy for
preventing gastric Cancer, 2014. https://www. iarc. fr/ en/ publications/
pdfs- online/ wrk/ wrk8/ Helicobacter_ pylori_ Eradication. pdf.
7. Liu WZ, Xie Y, Cheng H, et al. Chinese Society of Gastroenterology,
Chinese Study Group on Helicobacter pylori. Fourth Chinese
National Consensus Report on the management of Helicobacter
pylori infection. J Dig Dis 2013;14:211–21.
8. Lee SY. Current progress toward eradicating Helicobacter pylori
in East Asian countries: differences in the 2013 revised guidelines
between China, Japan, and South Korea. World J Gastroenterol
2014;20:1493–502.
9. Asaka M, Kato M, Sugiyama T, et al. Japan Helicobacter pylori
Eradication Study Group. Follow-up survey of a large-scale
multicenter, double-blind study of triple therapy with lansoprazole,
amoxicillin, and clarithromycin for eradication of Helicobacter pylori
in Japanese peptic ulcer patients. J Gastroenterol 2003;38:339–47.
10. Emilia G, Longo G, Luppi M, et al. Helicobacter pylori eradication
can induce platelet recovery in idiopathic thrombocytopenic purpura.
Blood 2001;97:812–4.
11. Gasbarrini A, Franceschi F, Tartaglione R, et al. Regression of
autoimmune thrombocytopenia after eradication of Helicobacter
pylori. Lancet 1998;352:878–78.
12. Hentschel E, Brandstätter G, Dragosics B, et al. Effect of ranitidine
and amoxicillin plus metronidazole on the eradication of Helicobacter
pylori and the recurrence of duodenal ulcer. N Engl J Med
1993;328:308–12.
13. Leodolter A, Kulig M, Brasch H, et al. A meta-analysis comparing
eradication, healing and relapse rates in patients with Helicobacter
pylori-associated gastric or duodenal ulcer. Aliment Pharmacol Ther
2001;15:1949–58.
14. Malfertheiner P, Megraud F, O'Morain C, et al. Current concepts in
the management of Helicobacter pylori infection: the Maastricht III
Consensus Report. Gut 2007;56:772–81.
15. Miwa H, Sakaki N, Sugano K, et al. Recurrent peptic ulcers in
patients following successful Helicobacter pylori eradication: a
multicenter study of 4940 patients. Helicobacter
2004;9:9–16.
16. Ogura K, Hirata Y, Yanai A, et al. The effect of Helicobacter pylori
eradication on reducing the incidence of gastric cancer. J Clin
Gastroenterol 2008;42:279–83.
17. Take S, Mizuno M, Ishiki K, et al. The effect of eradicating
Helicobacter pylori on the development of gastric cancer
in patients with peptic ulcer disease. Am J Gastroenterol
2005;100:1037–42.
18. Takenaka R, Okada H, Kato J, et al. Helicobacter pylori eradication
reduced the incidence of gastric cancer, especially of the intestinal
type. Aliment Pharmacol Ther 2007;25:805–12.
group.bmj.com on August 1, 2017 - Published by http://bmjopen.bmj.com/Downloaded from
10 HiroiS, etal. BMJ Open 2017;7:e015855. doi:10.1136/bmjopen-2017-015855
Open Access
19. Wong BC-Y, Lam SK, Wong WM, et al. Helicobacter
pylorieradication to prevent gastric cancer in a high-risk region of
China. JAMA 2004;291:187–94.
20. Wotherspoon AC, Doglioni C, Diss TC, et al. Regression of
primary low-grade B-cell gastric lymphoma of mucosa-associated
lymphoid tissue type after eradication of Helicobacter pylori. Lancet
1993;342:575–7.
21. Asaka M, Kato M, Takahashi S, et al. Japanese Society for
Helicobacter Research. Guidelines for the management of
Helicobacter pylori infection in Japan: 2009 revised edition.
Helicobacter 2010;15:1–20.
22. Hanamure Y, Honda A, Hokonohara A. Eradication therapy in the era
of Helicobacter pylori infection -Its issues-: current status and issues
of Helicobacter pylori treatment in Ichikikushikino-city (Kagoshima
Prefecture). Helicobacter Research 2014;18:74–7.
23. Fujimori K. The changes in Helicobacter pylori infection treatment:
is the number of infection reduced?. Helicobacter Research
2014;18:314–9.
24. Asaka M, Kato M, Sakamoto N. Roadmap to eliminate gastric cancer
with Helicobacter pylori eradication and consecutive surveillance in
Japan. J Gastroenterol 2014;49:1–8.
25. Sugano K, Osawa H, Satoh K. Clinical management of Helicobacter
pylori--the Japanese perspective. Dig Dis 2014;32:281–9.
26. Asaka M, Mabe K, Matsushima R, et al. Helicobacter
pylorieradication to eliminate gastric cancer: the Japanese strategy.
Gastroenterol Clin North Am 2015;44:639–48.
27. Asaka M, Kimura T, Kudo M, et al. Relationship of Helicobacter pylori
to serum pepsinogens in an asymptomatic Japanese population.
Gastroenterology 1992;102:760–6.
28. Cave DR. How is Helicobacter pylori transmitted? Gastroenterology
1997;113:S9–S14.
29. Take S, Mizuno M, Ishiki K, et al. Reinfection rate of Helicobacter
pylori after eradication treatment: a long-term prospective study in
Japan. J Gastroenterol 2012;47:641–6.
30. Okimoto T, Murakami K, Sato R, et al. Is the recurrence of
Helicobacter pylori infection after eradication therapy resultant from
recrudescence or reinfection, in Japan. Helicobacter 2003;8:186–91.
31. Fujisawa T, Kumagai T, Akamatsu T, et al. Changes in
seroepidemiological pattern of Helicobacter pylori and hepatitis
A virus over the last 20 years in Japan. Am J Gastroenterol
1999;94:2094–9.
32. Watabe H, Mitsushima T, Yamaji Y, et al. Predicting the development
of gastric cancer from combining Helicobacter pylori antibodies and
serum pepsinogen status: a prospective endoscopic cohort study.
Gut 2005;54:764–8.
33. Ueda J, Gosho M, Inui Y, et al. Prevalence of Helicobacter pylori
infection by birth year and geographic area in Japan. Helicobacter
2014;19:105–10.
34. Shiota S, Murakawi K, Suzuki R, et al. Helicobacter pylori infection in
Japan. Expert Rev Gastroenterol Hepatol 2013;7:35–40.
35. Ministry of Health, Labour and Welfare. Summary report of vital
statistics of Japan 2013 nal data, 2014. http://www. mhlw. go. jp/
toukei/ saikin/ hw/ jinkou/ kakutei13/ index. html. Japanese.
36. National Institute of Population and Social Security Research.
[Future population prediction in Japan]. 2012 http://www. ipss. go. jp/
syoushika/ tohkei/ newest04/ sh2401top. html.
37. Fock KM, Ang TL. Epidemiology of Helicobacter pylori
infection and gastric cancer in Asia. J Gastroenterol Hepatol
2010;25:479–86.
38. Ahmad MM, Rahman M, Rumi AK, et al. Prevalence of Helicobacter
pylori in asymptomatic population--a pilot serological study in
Bangladesh. J Epidemiol 1997;7:251–4.
39. Hoang TTH, Bengtsson C, Phung DC, et al. Seroprevalence of
Helicobacter pyloriinfection in urban and rural Vietnam. Clin Diagn
Lab Immunol 2005;12:81–5.
40. Xie C, Lu NH. Review: clinical management of Helicobacter pylori
infection in China. Helicobacter 2015;20:1–10.
41. Yim JY, Kim N, Choi SH, et al. Seroprevalence of Helicobacter pylori
in South Korea. Helicobacter 2007;12:333–40.
42. Lim SH, Kwon JW, Kim N, et al. Prevalence and risk factors of
Helicobacter pylori infection in Korea: nationwide multicenter study
over 13 years. BMC Gastroenterol 2013;13:104.
43. Moujaber T, MacIntyre CR, Backhouse J, et al. The seroepidemiology
of Helicobacter pylori infection in Australia. Int J Infect Dis
2008;12:500–4.
44. Mitchell H, Katelaris P. Epidemiology, clinical impacts and current
clinical management of Helicobacter pylori infection. Med J Aust
2016;204:376–80.
45. Sonnenberg A, Lash RH, Genta RM. A national study of Helicobactor
pylori infection in gastric biopsy specimens. Gastroenterology
2010;139:1894–901.
46. Cardenas VM, Mulla ZD, Ortiz M, et al. Iron deciency and
Helicobacter pylori infection in the United States. Am J Epidemiol
2006;163:127–34.
47. Goh KL, Chan WK, Shiota S, et al. Epidemiology of Helicobacter
pylori infection and public health implications. Helicobacter 2011;16
Suppl 1:1–9.
48. Ueda M, Kikuchi S, Kasugai T, et al. Helicobacter pylori risk
associated with childhood home environment. Cancer Sci
2003;94:914–8.
49. Konno M, Fujii N, Yokota S, et al. Five-year follow-up study of
mother-to-child transmission of Helicobacter pylori infection detected
by a random amplied polymorphic DNA ngerprinting method. J
Clin Microbiol 2005;43:2246–50.
50. Okuda M, Miyashiro E, Booka M, et al. Helicobacter pylori
colonization in the rst 3 years of life in Japanese children.
Helicobacter 2007;12:324–7.
51. The committee of the Japanese society for Helicobacter research.
[Guidelines for diagnosis and treatment of H. pylori infection in
Japan: 2016 revised edition. Tokyo: Sentan Igaku-Sha, 2016.
Japanese.
52. Murakami K, Sakurai Y, Shiino M, et al. Vonoprazan, a novel
potassium-competitive acid blocker, as a component of rst-line and
second-line triple therapy for Helicobacter pylori eradication: a phase
III, randomised, double-blind study. Gut 2016;65:1439–46.
group.bmj.com on August 1, 2017 - Published by http://bmjopen.bmj.com/Downloaded from
based on real-world data
observational study and simulation study
eradication therapy in Japan: retrospective
gastritis on the trends inHelicobacter pylori
Impact of health insurance coverage for
Shinzo Hiroi, Kentaro Sugano, Shiro Tanaka and Koji Kawakami
doi: 10.1136/bmjopen-2017-015855
2017 7: BMJ Open
http://bmjopen.bmj.com/content/7/7/e015855
Updated information and services can be found at:
These include:
References #BIBLhttp://bmjopen.bmj.com/content/7/7/e015855
This article cites 47 articles, 5 of which you can access for free at:
Open Access
http://creativecommons.org/licenses/by/4.0/
use, provided the original work is properly cited. See:
others to distribute, remix, adapt and build upon this work, for commercial
the Creative Commons Attribution (CC BY 4.0) license, which permits
This is an Open Access article distributed in accordance with the terms of
service
Email alerting box at the top right corner of the online article.
Receive free email alerts when new articles cite this article. Sign up in the
Collections
Topic Articles on similar topics can be found in the following collections
(200)Gastroenterology and hepatology
(2087)Epidemiology
Notes
http://group.bmj.com/group/rights-licensing/permissions
To request permissions go to:
http://journals.bmj.com/cgi/reprintform
To order reprints go to:
http://group.bmj.com/subscribe/
To subscribe to BMJ go to:
group.bmj.com on August 1, 2017 - Published by http://bmjopen.bmj.com/Downloaded from
