Primary Document Analysis Chart

Document #: ___1___ Date Analyzed: _1___/__19___

Type of Research Study in Journal

1. Document
(Format)
Date(s) of 2014
2. Document
3. Source UC Berkeley
Author/Creator Ndola Prata MD, MSc public health physician and medical demographer from Angola.
4. (Position)
Suzanne Bell. Assistant Scientist. Bloomberg School of Public Health. I think this is
her.

Professor Dr. Md. Abdul Quaiyum - University of Dhaka

Organisation: University of Dhaka
Role: Chairman, Department of Applied Chemistry and Chemical Technology
Country: Bangladesh

Audience, if
5. specified
6. Document A. Background, Setting, Bangladesh may reach the 5th MDG, but skilled birth
Information Dates Conducted, and attendance is still low. Misoprostol may be able to
Population Details reduce deaths from PPH.

six districts of the Rangpur Division in Bangladesh

from May 2009 through September 2010

B. Methods—Review or
RCT? Field staff received training on misoprostol
administration and use of a blood measurement tool, as
well as danger signs in pregnancy, referral procedures,
stages of labor, newborn resuscitation, etc. Both the
misoprostol and the blood measurement tool were
added to the existing clean delivery kits being
distributed. 118, 500 women enrolled in the study, and
77,337 delivered during the study period. 87%
delivered at home. PPH and misoprostol usage (if they
used it or not) statistics were recorded based on
women’s self-reporting and verbal autopsies. The data
was then analyzed using the Monte Carlo modeling
technique using Crystal Ball 7.
 C. Results—Significant or
not?

“Using project level misoprostol coverage (69%), the

mean number of PPH deaths expected was 40(standard
deviation = 8.01) per 100,000 live births. Assuming no
misoprostol coverage (0%), the mean number ofPPH
deaths expected was 51 (standard deviation = 9.30) per
100,000 live births. For low misoprostol coverage
(40%),the mean number of PPH deaths expected was
45 (standard deviation = 8.26) per 100,000 live births,
and for high misoprostol coverage (80%), the mean
number of PPH deaths expected was 38 (standard
deviation = 7.04) per100,000 live births”

D. Interpretation—What
does this say about
misoprostol or
contraception? Is this More misoprostol coverage can reduce maternal
study generalizable? mortality.
Yes, data from other countries was incorporated for
model building.
7 percent reduction in overall maternal mortality in
Bangladesh—that is about 23% of all PPH caused
maternal mortality. The other 88% might need stronger
uterotonic, more uterotonics, or other interventions.
Not a huge difference.

E. Corroboration between
studies if applicable
F. Additional
logistics—costs, extra
details, etc.
7. Possible Bias ● It’s possible that women who lived closer to healthcare facilities were more
(up to 3 points) likely to receive misoprostol and use it, as well as also receive lifesaving care.
● Although unlikely, it could be that women who used the tools (misoprostol,
mat) were more likely to seek care because of increased motivation and
knowledge. Thus, the decreased mortality could have been more because of
decrease of mortality after PPH, not decrease in PPH.
● MMR were lower than in other studies; could have been that they were
transferred and delivered in hospitals, better access to healthcare; thus, might
be conservative estimates.
● Categories of death were different.
 ● Verbal autopsy might not have been very reliable; there was increased
awareness of PPH among the community. Could have been misclassified.
● This population received antenatal care and clean delivery kits, so they had
quite linear improvements. Might not be as linear in other areas.
● Incomplete data for one case.
8. Lack of What was in the existing CDK?
Information
(up to 3 points)
9. Things I don’t How exactly did the different categories affect the data?
understand in the So other RCTS were incorporated into the model?
study

Document #: __2___ Date Analyzed: _1___/__24___

Type of Research Study in Journal

1. Document
(Format)
Date(s) of November 6, 2019
2. Document
3. Source BMC Pregnancy and Childbirth
Author/Creator Gizachew Tadele Tiruneh
4. (Position) JSI Research & Training Institute, Inc./ The Last Ten Kilometers (L10K) Project, Addis
Ababa, Ethiopia

Bereket Yakob
Members of the National Reproductive, Maternal, Newborn, Child, Adolescent Health,
and Nutrition (RMNCAH-N) Research Advisory Council (RAC), Addis Ababa, Ethiopia

Wubegzier Mekonnen Ayele

Members of the National Reproductive, Maternal, Newborn, Child, Adolescent Health,
and Nutrition (RMNCAH-N) Research Advisory Council (RAC), Addis Ababa, Ethiopia
Addis Ababa University School of Public Health, Addis Ababa, Ethiopia

Wubegzier Mekonnen Ayele

Members of the National Reproductive, Maternal, Newborn, Child, Adolescent Health,
and Nutrition (RMNCAH-N) Research Advisory Council (RAC), Addis Ababa, Ethiopia
Addis Ababa University School of Public Health, Addis Ababa, Ethiopia

Muluneh Yigzaw
Members of the National Reproductive, Maternal, Newborn, Child, Adolescent Health,
and Nutrition (RMNCAH-N) Research Advisory Council (RAC), Addis Ababa, Ethiopia

Meselech Assegid Roro

Members of the National Reproductive, Maternal, Newborn, Child, Adolescent Health,
and Nutrition (RMNCAH-N) Research Advisory Council (RAC), Addis Ababa, Ethiopia

Araya Abrha Medhanyi

Members of the National Reproductive, Maternal, Newborn, Child, Adolescent Health,
and Nutrition (RMNCAH-N) Research Advisory Council (RAC), Addis Ababa, Ethiopia
 Etenesh Gebreyohannes Hailu
Members of the National Reproductive, Maternal, Newborn, Child, Adolescent Health,
and Nutrition (RMNCAH-N) Research Advisory Council (RAC), Addis Ababa, Ethiopia
Federal Ministry of Health, Addis Ababa, Ethiopia

Etenesh Gebreyohannes Hailu

Members of the National Reproductive, Maternal, Newborn, Child, Adolescent Health,
and Nutrition (RMNCAH-N) Research Advisory Council (RAC), Addis Ababa, Ethiopia
Federal Ministry of Health, Addis Ababa, Ethiopia

Audience, if
5. specified
6. Document A. Background, Setting, Community distribution of misoprostol to women in labor
Information Dates Conducted, and might be one of the best ways to prevent PPH, but there
Population Details have been concerns that it could reduce facility delivery
or lead to misuse of medication.

B. Methods—Review or
RCT? Review. All literature about community-distribution of
misoprostol in English were included, no specification on
publication time.

This was a scoping review to synthesize evidence on

effects of taking misoprostol, including peer-reviewed
studies on misoprostol implementation from PubMed,
Cochrane Review Library, Popline, and Google Scholar.
3 qualitative studies
7 observational studies
4 experimental or quasi-experimental studies

Quality scores were given. A random effects

meta-analysis model was used to pool estimates of
facility birth in intervention studies.

C. Results—Significant or
not?

“The pooled analysis of experimental and

quasi-experimental studies involving 7564 women from
four studies revealed that there was no significant
difference in rates of facility delivery among the
misoprostol and control groups [OR 1.011; 95% CI:
0.906–1.129]”
 Self-administration before delivery was reported in less
than 2% of women. Most women used them as instructed.

D. Interpretation—What
does this say about
misoprostol or
contraception? Is this Concerns of misuse are unfounded; it is very unlikely.
study generalizable? Further, community-based distribution of misoprostol has
not negatively affected delivery rates; some studies even
show an increase. Misoprostol is safe and effective for
use in PPH when oxytocin and timely transfer to higher
care is not possible. Study must be generalizable because
it’s a scoping review of all literature.

E. Corroboration between Another study that supports usage of misoprostol, as in

studies if applicable Doc 1
F. Additional
logistics—costs, extra
details, etc.
7. Possible Bias ● Might be missing some relevant studies since only published studies in English
(up to 3 points) were included.
● Only a small number of articles met inclusion criteria, and few thorough studies
investigated negative effects of misoprostol usage. Couldn’t be pooled together.
8. Lack of What were the costs like for misoprostol distribution in these studies as a whole? What
Information was the overall efficacy?
(up to 3 points)
9. Things I don’t Why didn’t they include the overall efficacy of misoprostol in this review?
understand in the
study

Document #: __3___ Date Analyzed: _1___/__24___

Type of Research Study in Journal

1. Document
(Format)
Date(s) of July 15, 2013
2. Document
3. Source Cochrane Database of Systematic Reviews
Author/Creator G Justus Hofmeyr
4. (Position) Department of Obstetrics and Gynaecology, East London Hospital Complex,
University of the Witwatersrand, University of Fort Hare, Eastern Cape Department of
Health, East London, South Africa
 A Metin Gülmezoglu
UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and
Research Training in Human Reproduction, Department of Reproductive Health and
Research, World Health Organization, Geneva, Switzerland

Natalia Novikova
Department of Obstetrics and Gynaecology, East London Hospital Complex, Walter
Sisulu University, East London, South Africa

Theresa A Lawrie
The Cochrane Gynaecological Cancer Group, Royal United Hospital, Bath, UK
Audience, if
5. specified
6. Document A. Background, Setting, Misoprostol is more easily distributed on the
Information Dates Conducted, and community level than injectable medication, but it
Population Details might have adverse effects unrelated to blood loss.

Population: “Pregnant women ≥ 24 weeks' gestation

who received misoprostol during the third stage of
labour or in the postpartum period, versus placebo/no
treatment or other uterotonics for prevention or
treatment of postpartum haemorrhage (PPH). We
included studies conducted in women who delivered by
caesarean section.”

B. Methods—Review or
RCT? Review. All literature in the Cochrane Pregnancy and
Childbirth Group’s Trials Register on January 11, 2013.

Including randomized trials with preg woman who

received misoprostol during postpartum versus
placebo/no treatment and reporting on maternal death,
severe morbidity, pyrexia.

Did not include cluster or quasi-randomised trials

because no suitable ones could be identified.

Included 78 studies of 59,216 women and excluded 34

studies.

C. Results—Significant or No statistically significant difference in maternal

not? mortality for misoprostol compared with control groups
overall or for trials of misoprostol versus placebo or for
misoprostol versus other uterotonics. There was a
statistically significant difference in the composite
outcome of maternal death/severe morbidity for
misoprostol versus placebo, but when hyperpyrexia
was excluded, there was no significant difference.
 Pyrexia greater than 38 Celsius was increased with
misoprostol compared with controls, and effect was
greater for trials using 600 micrograms or more than
for those using 400 micrograms or less. All 11 deaths
“in the misoprostol arms” occurred in studies of
misoprostol ≥ 600 µg.

Misoprostol does not seem to increase or reduce severe

morbidity excluding hyperpyrexia when used to treat
PPH, but it also did not increase or decrease maternal
mortality. This study supports usage of the lowest
effective dose.

Considerable heterogeneity in the effect on pyrexia.

From 2.3% pyrexia in control to 10.8% pyrexia in

misoprostol group.

D. Interpretation—What
does this say about
misoprostol or Misoprostol is associated with an increased risk of
contraception? Is this hyperpyrexia, but it did not help with maternal
study generalizable? mortality. What’s the point then?

Study does not address effectiveness of misoprostol for

blood loss, covered in separate Cochrane reviews.

Hyperpyrexia can be life-threatening and is very

unpleasant for many women. It is one of the biggest
risks. There’s no difference in blood loss for 600
micrograms versus 400micrograms.

While it might be intuitive to think reduced blood loss

leads to reduced mortality, not necessarily that
straightforward. Can have other adverse effects on
many organ systems.
E. Corroboration between Other studies have not identified the same results. Why
studies if applicable does this study have such different ones?
F. Additional
logistics—costs, extra
details, etc.
7. Possible Bias ● Some studies had high risks of performance or detection bias
(up to 3 points) ● The study itself says that the number of maternal deaths is too small for
meaningful statistical analysis, could be a small reduction or a large increase
with misoprostol. “The range of plausible effects lies between a small (18%)
reduction and a large (5.28 times) increase with misoprostol. “
● Composite outcome might have been improved by including other outcomes
like blood transfusions that could be better indicators of severe morbidity.
 ● Hyperpyrexia may have been underestimated along with other severe morbidity
because some studies didn't do a quantitative assessment of pyrexia but
included over severe morbidity, and so they included it in meta-analysis.
● Although the authors tried to contact the authors of studies where maternal
deaths were not reported, some could not be reached.

●
8. Lack of Are the studies in the Cochrane database reliable?
Information Did they use the biased studies?
(up to 3 points)
9. Things I don’t
understand in the
study
Excluded 4th misoprostol study because I realized that it didn’t fit the hypothesis well.

Document #: __4___ Date Analyzed: _1___/__24___

Type of Research Study in Journal

1. Document
(Format)
Date(s) of July 10, 2012
2. Document
3. Source The Lancet
Author/Creator Dr Saifuddin Ahmed, PhD Department of Population, Family and Reproductive
4. (Position) Health, Bloomberg School of Public Health, Johns Hopkins University,
Qingfeng Li, MA
Affiliations
Department of Population, Family and Reproductive Health, Bill and Melinda Gates
Institute for Population and Reproductive Health, Bloomberg School of Public Health,
Johns Hopkins University, Baltimore, MD, USA

Li Liu, PhD
Affiliations
Department of International Health, Bill and Melinda Gates Institute for Population
and Reproductive Health, Bloomberg School of Public Health, Johns Hopkins
University, Baltimore, MD, USA
Professor Amy O Tsui, PhD
Department of Population, Family and Reproductive Health, Bill and Melinda Gates
Institute for Population and Reproductive Health, Bloomberg School of Public Health,
Johns Hopkins University, Baltimore, MD, USA
Audience, if
5. specified
6. Document A. Background, Setting,
Information Dates Conducted, and
Population Details
Contraceptive rates reduced maternal mortality rates in
the past and can continue to do so in the future.
“Family planning directly reduces the number of
maternal deaths because it reduces the chance of
pregnancy and the associated complications (exposure
reduction), lowers the risk of having an unsafe abortion
(vulnerability reduction), delays first pregnancy in
young women who might have premature pelvic
development, and reduces hazards of frailty from high
parity and closely spaced pregnancies. “

Reduces the number of pregnancies and the number of

high-risk pregnancies: too early, too late, too many, or
too frequent etc.
B. Methods—Review or
RCT? Review. “We extracted relevant data from the Maternal
Mortality Estimation Inter-Agency Group (MMEIG)
database, the UN World Contraceptive Use 2010
database, and the UN World Population Prospects 2010
database, and applied a counterfactual modelling
approach (model I), replicating the MMEIG (WHO)
maternal mortality estimation method, to estimate
maternal deaths averted by contraceptive use in 172
countries. ”
C. Results—Significant or “We estimate, using model I, that 342 203 women died
not? of maternal causes in 2008, but that contraceptive use
averted 272 040 (uncertainty interval
127 937–407 134) maternal deaths (44% reduction), so
without contraceptive use, the number of maternal
deaths would have been 1·8 times higher than the 2008
total. Satisfying unmet need for contraception could
prevent another 104 000 maternal deaths per year (29%
reduction).”

D. Interpretation—What
does this say about Family planning can significantly reduce maternal
misoprostol or mortality in the coming years, but full coverage is not
contraception? Is this realistic. Reducing unmet need for contraception is
study generalizable? incredibly important.

E. Corroboration between NA. Looks to be more effective than misoprostol.

studies if applicable
F. Additional
logistics—costs, extra
details, etc.
7. Possible Bias ● Data it is based on might not be accurate; direct measures of maternal health in
(up to 3 points) developing countries are known to be very poor.
● Some data is estimated. “the MMEIG's maternal mortality ratio database has
many model-based estimates, which are driven by assumptions about data
distributions, imputation of missing data, and relevant covariates. “
 ● Couldn’t break down maternal mortality to decrease in the number of births and
decrease in high-parity births.
8. Lack of What are the costs for contraceptive distribution? What kinds of contraception work
Information best?
(up to 3 points)
9. Things I don’t The statistical analysis
understand in the
study