Chen et al.

Trials 2014, 15:128

http://www.trialsjournal.com/content/15/1/128

RESEARCH

TRIALS
Open Access

A retrospective survey of quality of reporting on

randomized controlled trials of metformin for
polycystic ovary syndrome
Baoying Chen*, Jian Liu, Chun Zhang and Minyan Li

Abstract
Background: From previous reviews, there still have been controversies over the effect of metformin (MET) on
reproductive function in PCOS patients. The reasons for the inconsistent findings especially lie in the transparency
and accuracy of randomized controlled trials (RCTs) reports. However, we could find no data about the quality of
RCTs reporting in MET for PCOS. Thus, a retrospective survey related to the quality of reporting in MET for PCOS
was conducted.
Methods: A retrospective survey was conducted by two investigators. Two investigators assessed the quality of
overall reporting and key methodological factors reporting using items from the CONSORT 2010 statement.
Results: A total of 39 RCTs were included in full text. The median overall quality score was 9, with a minimum of 2
and a maximum of 13. Good or general reporting existed in 11 items with positive rate of more than or equal to
50%. The median score of key methodological items was 4 with a minimum of 0 and a maximum of 5.
Randomization, allocation concealment, blinding, baseline characteristics and intention-to-treat (ITT) analysis were
reported in 26 (67%), 19 (49%), 20 (51%), 38 (97%) and 17 (44%) of the 39 RCTs, respectively. After adjustment, the
mean overall score increased by about 1.71 for manuscripts with funding source (95% CI, 0.18 to 3.24), while it
increased by about 3.51 for manuscripts published in one year increment (95% CI, 1.82 to 5.19). There was a
relatively close, significant correlation (r = 0.589, P < 0.001) between the score of overall reporting quality and year of
publication.
Conclusion: Although the overall reporting quality of RCTs in MET for PCOS has improved over time, reporting of
key methodological items remains poor. Reporting of RCTs on MET for PCOS should keep up with the standards of
the CONSORT statement.
Keywords: Metformin, Quality of reporting, Randomized controlled trials, Polycystic ovary syndrome, The CONSORT
Statement

Background
Polycystic ovary syndrome (PCOS) is characterized by
chronic anovulation (failure or absence of ovulation) and
hyperandrogenism (excessive production of male hormones
in women) with clinical manifestations of irregular menstrual cycles, infertility, hirsutism, and acne [1], which is a
common condition affecting women of reproductive age
in 5 to 10% [2].

* Correspondence: [email protected]
Department of Traditional Chinese Medicine, The First Peoples Hospital of
Shunde, Foshan, PR China

Administration of clomiphene citrate (CC) is the

standard treatment for PCOS patients with anovulatory
infertility. However, clomiphene resistance (failure to ovulate after taking clomiphene) is common, occurring in approximately 15 to 40% of women with PCOS [3]. In 2008,
it was reported that insulin resistance was a significant
contributor to the pathogenesis of PCOS [4]. Because of
the insulin resistance in the pathogenesis of PCOS, metformin (MET), a biguanide and insulin-sensitizing drug
used in the treatment of type 2 diabetes mellitus, was
applied to the treatment of infertile women with PCOS
before or during the ovulation induction [5].

2014 Chen et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly credited.

Chen et al. Trials 2014, 15:128

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Several systematic reviews and meta-analyses [6-13]

have evaluated the efficacy of metformin in the treatment
of anovulation because of PCOS. Most of these reviews
concluded that metformin monotherapy represented a
safe and valid therapeutic option for improving ovulation
in PCOS patients. One review [13] concluded that combination of MET and CC could gain advantage over a
single administration in the ovulation induction and
pregnancy rate, but another review [12] concluded this
combination was no better than monotherapy (MET
alone or CC alone). Moreover, there still have been controversies over the effect of MET on reproductive function in PCOS patients [14-17].
Randomized controlled trials (RCTs) are widely accepted as the gold standard for accumulating strong
evidence for any health care intervention. Moreover,
quality of reporting is essential for guiding journal
peer-review decisions and experts recommendations,
conducting unbiased meta-analysis and influencing
our interpretation of evidence [18]. The reasons for
the inconsistent findings of above reviews lie in the
bias of literature search and screening and especially
the transparency and accuracy of RCT reports. The
Consolidated Standards of Reporting Trials (CONSORT)
statement is an international consensus expert guideline
developed in 1996 and last updated in 2010, aimed at
improving the reporting quality of published RCTs [19].
The CONSORT is widely accepted in the field of clinical
trials and is supported by a growing number of health
care journals and editorial groups.
However, we could find no data about the quality of
RCTs reporting in MET for PCOS. Thus, a retrospective
survey related to the quality of reporting in MET for
PCOS was conducted. The aim of this study was to assess the overall quality of published articles of randomized trials in MET for PCOS with a special focus on the
key methodological items that safeguard against biases,
namely appropriate randomization, allocation concealment, blinding, baseline characteristics and analysis according to intention-to-treat (ITT) principle. Secondarily,
we also aimed at determining factors associated with
better reporting quality.

Methods
Search strategy

A systematic and comprehensive literature search was

conducted with the aim of identifying published prospective RCTs of MET for PCOS. No resources were available
to search literature published in languages other than
English.
The following databases were searched from their inception through February 2013: MEDLINE, EMBASE,
the Cochrane Central Register of Controlled Trials
(CENTRAL), and CINAHL.

Page 2 of 8

Keywords were approved by all the authors and included

PCOS, polycystic ovary syndrome, metformin, MET,
clomiphene citrate, CC, randomized trials, RCT. Eligible articles were identified by successive screening of
titles and abstracts. Then the references section of each
printed article was screened to identify any additional
eligible articles.
Inclusion and exclusion criteria

Types of studies: only RCTs of MET for PCOS were

identified and selected for the analysis. Specifically, retrospective, non-randomized, cross-over RCTs, case-control,
and quasi-randomized trials, abstracts in conference and
case reports/series were excluded.
The criteria in terms of PCOS diagnosis had to be consistent with those as follows: oligo- or anovulation, clinical
or biochemical signs of hyperandrogenism and polycystic
ovaries visible with ultrasound. The RCTs on the effects
on MET in patients who received gonadotrophins for IVF
and not-IVF cycles were also included. Several different
types of interventions were analyzed: MET versus placebo,
MET versus CC, MET plus CC versus CC, MET plus CC
versus MET. We also included trials in which MET combined with other interventions as the treatment group (for
example, MET plus lifestyle versus placebo plus lifestyle,
MET plus rFSH versus rFSH). The primary comparison
was always between MET and the other treatment. Outcomes included live birth rate, rates of ovulation, pregnancy, abortion and discontinuation for adverse events.
Assessment of reporting quality
Rating of overall reporting quality

An overall quality score with 13 items from the CONSORT

2010 statement was used (Table 1). Each item was
scored 1 if it was reported and 0 if it was not clearly, or
definitely not stated. These were among the items selected by previous evaluation studies of the CONSORT
statement [20-23].
Rating of key methodological items

Five key methodological categories of randomization,

allocation concealment, blinding, baseline characteristics
and ITT analysis have been assessed separately because
they relate to potential sources of bias [24-26]. We then
developed eight yes/no items (Table 2), wording so
that emphasis was placed on quality of reporting rather
than adequacy of trial design. Each item was scored 1 if
the method was appropriate and 0 if inappropriate or if
the reporting was unclear.
Data extraction

One of the investigators (Minyan Li) looked at the title,

abstract and methodology of all the published papers
to identify them as RCTs. General information (year of

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Table 1 Overall quality of reporting rating using items from the CONSORT statement (n = 39)
Item Criteria

Description

Number. of %
positive trials

95% CI

Cohens
coefficient

95% CI

Randomized
in the title
or abstract

Study identified as a randomized controlled in the

title or abstract

36

92 84 to 100

Background

Adequate description of the scientific background and

explanation of rationale

38

97 92 to 100

0.62

0.35 to 0.95

Trial design

Description of trial design (such as parallel, factorial)

including allocation ratio

34

87

0.74

0.52 to 0.98

Participants

Description of the eligibility criteria for participants

36

92 84 to 100

0.92

0.83 to 1.00

Interventions

Details of the interventions intended for each group

35

90 80 to 100

0.63

0.42 to 0.98

Outcomes

Definition of primary (and secondary when appropriate)

outcome measures

23

59

43 to 75

0.81

0.65 to 0.99

Sample size

Description of sample size calculation

19

49

32 to 65

0.78

0.54 to 0.97

12

Statistical
methods

Description of the statistical methods used to compare groups

for primary outcomes, subgroup analyses, or adjusted analyses

29

74

60 to 89

0.68

0.43 to 0.96

13

Flow chart

Details on the flow of participants through each stage of the trials

(number of patients randomly assigned, receiving intended
treatment, completing the protocol and analyzed)

21

54

37 to 70

0.93

0.85 to 1.00

14

Recruitment

Dates defining the periods of recruitment and follow-up

20

51

35 to 68

0.54

0.36 to 0.92

17

Outcomes and
estimation

For each primary and secondary outcome, a summary of results

for each group is given, and the estimated effect size and its
precision (for example, 95% CI)

20

51

35 to 68

0.86

0.73 to 0.99

18

Ancillary
analyses

Clear statement of whether subgroup/adjusted analyses were

prespecified or exploratory

20

51

35 to 68

0.66

0.31 to 0.97

19

Harms

Description of all important adverse events in each group

16

41

25 to 57

0.73

0.62 to 0.96

publication, journal of publication, impact factor of

journal, collaboration research of different countries,
region in which trials were conducted, funding source,
choice of comparator interventions) were extracted (by
Chun Zhang). Relevant studies were then photocopied
with the authors names, date and institution excluded
for following rating by two assessors (Baoying Chen and
Jian Liu). Two independent assessors (Baoying Chen and
Jian Liu) blinded to each others ratings, completed the
rating form independently. Cohens -statistic was calculated to assess agreement between two assessors. Agreement was judged as poor if 0.20; fair if 0.20 lower than
0.40; moderate if 0.40 lower than 0.60; substantial
if 0.60 lower than 0.80; good if higher than 0.80; and
perfect if = 1 [20]. Discrepancies were reviewed in detail
and subsequently settled by consensus.
Data analysis

The characteristics of the publications, scores of overall

reporting quality and five methodological items were
then described by descriptive analysis. To identify factors
associated with the overall quality of publications, we
used this overall score as the outcome variable and the
characteristics of the publications as independent variables
which was modeled using linear regression. Only variables
that were significant at P 0.10 in the univariate models

76 to 98

were used in a multivariable regression model for selecting

significant variables. Variables significant at the 5% level
in the final multivariable model were considered as significant predictors. To analyze the relationship between
the score of overall reporting quality and year of publications, scatter plot and Pearson correlation analysis
were performed.
To identify factors associated with methodological
quality, we used this methodological score as the outcome
variable in the regression analyses. As the outcome variable can be considered as a count, we relied on a Poisson
regression model and adjusted the variance empirically.
Descriptive statistical analysis, linear regression analysis,
scatter plot and Pearson correlation were performed using
SPSS version 20.0 (SPSS, Chicago, IL, USA). Analysis
of Poisson regression model and Cohens -statistics
were performed using the SAS software, version 9.1
(SAS Institute, Inc, Cary, NC, USA). Database of RCTs
in MET for PCOS are provided in Additional file 1.

Results
The RCTs selection process is outlined in Figure 1. The
researchers applied the search method to find 225 reports
related to the topic, among which 35 reports of duplicates,
29 reports of non-MET therapy or PCOS, 23 reports of
animal experiments, reviews and comments are excluded.

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Table 2 Reporting quality of key methodologic items (n = 39)

95% CI

Cohens
coefficient

95% CI

67

51 to 82

0.83

0.72 to 0.98

19

49

31 to 64

0.71

0.55 to 0.94

Whether or not participants, those administering the

interventions, or those assessing the outcomes were
blinded to group assignment

20

51

27 to 55

0.72

0.48 to 0.95

An outline of baseline demographic and clinical

characteristics of each group

38

97 92 to 100

0.65

0.49 to 0.97

17

44

0.92

0.80 to 0.99

Item

Criteria

Description

Randomization

Description of the method used to generate the

random sequence

26

9 and 10 Allocation concealment

and implementation

Description of the method used to implement the

random allocation sequence assuring the concealment
until interventions are assigned

11

Blinding

15

Baseline data

16

Intention-to-treat analysis Number of participants in each group included in each

analysis and whether it was done by intention-to-treat

One hundred and thirty-eight reports were obtained for

further evaluation. Then researchers viewed the full text
of all potentially eligible reports were obtained and
picked out 16 case reports, 34 case series reports and 32
non-randomized controlled reports. Then, 56 RCTs preliminarily were adopted. After carefully reselecting, we
pick out nine duplicated published reports and eight reports not comparing MET and the other treatment. A

Figure 1 Flowchart of the article selection process.

Number of %
positive trials

27 to 60

total of 39 relevant RCTs were included in the final

analysis.
Characteristics of included trials

The characteristics of RCTs included in the final analysis

are described in Table 3. Counting the number of articles,
frequency, which refers to RCTs of MET for PCOS, was
found to be increasing over time: from 7 (17.9%) in 1996

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Table 3 Characteristics of included randomized controlled

trials (RCTs) in metformin (MET) for polycystic ovary
syndrome (PCOS)
Features of included RCTs

Number of
%
studies (n = 39)

Year of publication
1996 to 2001

17.9

2002 to 2007

12

30.8

2008 to February 2013

20

51.3

Before

17.9

After

32

82.1

North America

15.4

Europe

16

41.0

Others

17

43.6

Yes

19

48.7

No

20

51.3

Revised CONSORT 2001

Regions in which RCTs were conducted

Sources of trial funding

Collaboration of different countries

Yes

20.5

No

31

79.5

Placebo

16

41.0

Sole intervention

11

28.2

MET plus other therapies

7.7

Some of above combinations

23.1

Choice of comparator interventions

Journals with most frequently published

The Journal of Clinical Endocrinology &
Metabolism

23.1

Fertility and Sterility

17.9

Human Reproduction

15.4

The New England Journal of Medicine

7.7

14

35.9

0.00 to 2.99

10

25.6

3.00 to 5.99

24

61.5

6.00-

10.3

Eleven other journals

Impact factors of included journalb

Abbreviations: CONSORT, Consolidated Standards of Reporting Trials; MET,

metformin; PCOS, polycystic ovary syndrome; RCT, randomized controlled trial.
a
Each journal published fewer than three RCTs.
b
One journal (Acta Med Indones) did not have an impact factor.

to 2001 to 20 (51.3%) in 2008 to February 2013. The

percentages of RCTs from North America and Europe
were 15.4% and 41.0%. More than half of included trials
neither got funding nor collaborated with researchers
from different countries. Sixteen RCTs (41.0%) chose
placebo as the comparator intervention. The RCTs were
published predominantly in three journals, namely The

Journal of Clinical Endocrinology & Metabolism (23.1%),

Fertility and Sterility (17.9%) and Human Reproduction
(15.4%).
Quality of reporting
Rating of overall reporting quality

The ratings of overall quality of reporting are listed in

Table 1. When the 39 RCTs were considered, the median
overall quality score was 9, with a minimum of 2 and a
maximum of 13. Good or general reporting existed in 11
items with positive rate of more than or equal to 50%,
while items of sample size and harms presented less
good reporting with positive rates of less than 50%.
Inter-rater agreements are reported for each item in
Tables 1 and 2. A substantial, good, or perfect agreement was observed for 17 of 18 items. The inter-rater
agreement was considered as moderate for item 14 (28
February 2013).
Rating of Key Methodological Items

Randomization, allocation concealment and implementation, blinding, baseline characteristics and ITT analysis
were reported in 26 (67%), 19 (49%), 20 (51%), 38 (97%)
and 17 (44%) of the 39 RCTs, respectively (Table 2).
The median score of key methodological items was 4
with a minimum of 0 and a maximum of 5. Among the
39 studies, 1 (3%) did not report any of the five key
methodological items (Table 2).
Exploratory analysis: factors associated with better
reporting quality

In univariate analyses, year of publication and funding

source were associated with an increased overall score.
After adjustment, the multivariable linear regression
model suggested that these two factors remained significant predictors of overall quality. Moreover, the mean
overall score increased by about 1.71 for manuscripts
with funding source (95% CI, 0.18 to 3.24; P < 0.05), while
it increased by about 3.51 for manuscripts published in
one year increment (95% CI, 1.82 to 5.19; P < 0.001)
(Table 4).
With regard to the methodological score, using univariate Poisson regression, no variable was included in
the model.
Table 4 Multivariable linear regression analysis for
factors associated with better overall score from the
CONSORT statement (n = 39)
Variables

SE

95% CI

Constant

5.52

0.81

6.80

< 0.001

3.87 to 7.17

Funding source

1.71

0.75

2.27

0.030

0.18 to 3.24

Year of publication

3.51

0.83

4.22

< 0.001

1.82 to 5.19

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Trends of reporting quality

From Table 4, we saw the factor of year of publication is

a powerful predictor for overall reporting quality with its
coefficient 3.51. We want to know how the trend of
overall reporting quality in RCTs of MET for PCOS will
be with year increasing. There was a relatively close,
significant linear correlation (r = 0.589, P < 0.001) between the score of overall reporting quality and year of
publications (Figure 2).

Discussion
This study demonstrated that the quality of reporting in
RCTs on MET for PCOS was suboptimal especially in key
methodological items. This indicated that RCTs on MET
for PCOS syndrome needed improvement to meet the
level of reporting quality required by the CONSORT
statement. It is important to follow the guidelines of the
CONSORT statement for RCTs on MET for PCOS for
two reasons. First, inconsistent findings of reviews [12,13]
or controversies [14-17] still existed in the effect of MET
on reproductive function in PCOS patients. Transparency
and accuracy of RCT reports will benefit the evidencebased information extracting, assessing the validity of the
results and medical decision making. Second, standardized
report format allowed the reader to obtain more information in a short time. Detailed and transparent reporting
made it easy to replicate the study and avoid the waste of
medical resources.

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We identified five areas where information was insufficient or inadequate in most studies. These areas are sample size, harms, allocation concealment, blinding and ITT
analysis. Most importantly, the reporting quality of key
methodological items was poor. Our results are in agreement with similar studies assessing the reporting quality
of RCTs published in other medical journals [27-29]. All
of them showed a suboptimal reporting quality, with key
methodologies being usually the most poorly reported
items. Allocation concealment, blinding, and ITT analysis
are critical in avoiding selection, performance/detection,
and attrition bias, respectively. An overestimation of
treatment effects has been demonstrated in trials with
inadequate key methodological design comparison with
trials that adequately reported these methodological
items [19].
Understanding the importance of transparency in reporting clinical trials, an international team, including
epidemiologists, statisticians and journal editors, developed the Consolidated Standards for Reporting Trials
(CONSORT) statement in 1996 [30]. The CONSORT
statement is an evidence-based set of recommendations
for reporting two-arm, parallel-group RCTs, including a
minimum set of items to be reported pertaining to the
rationale, design, analysis, and interpretation of the trial
(that is the CONSORT checklist) and a diagram describing
flow of participants through a trial (that is a flow diagram). It is intended to facilitate the complete and

Figure 2 Correlation between the score of overall reporting quality and year of publications.

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transparent reporting of RCTs and in turn aid in their

critical appraisal and interpretation. The effectiveness of
CONSORT in improving the reporting quality of RCTs
has been widely evaluated. A 2008 systematic evaluation
investigated whether there had been an improvement in
quality of reporting for RCTs since the publication of
CONSORT statements [31]. The results of this study suggest that general standards of reporting for acupuncture
trials have significantly improved since the introduction
of the CONSORT statement in 1996 [31]. However, the
magnitude of improvement varied considerably among
included studies. A possible explanation for this variability is the lack of consistency in enforcing the use of
the CONSORT checklist among CONSORT adopter
journals. Cobo et al. [32] developed a RCT to investigate
the effect of an additional review based on reporting
guidelines such as CONSORT on quality of manuscripts.
They found that it is difficult for authors in adhering to
high methodological standards at the latest research
phases; to boost paper quality and impact, authors should
be aware of future requirements of reporting guidelines at
the very beginning of their study [32].
Interestingly, we find the overall reporting quality
of RCTs in MET for PCOS is improving with the
year increasing, which indicates that more and more
researchers and editors are realizing the importance
of reporting in RCTs due to the widely adoption and
promotion of CONSORT. The effect of CONSORT in
reporting RCTs of MET for PCOS still needs evaluation. A
future evaluation (for example, before and after study,
RCT) of the reporting quality after CONSORT endorsement would be useful in assessing the effectiveness of this
measure. Meanwhile, our finding that the overall reporting
quality based on the CONSORT statement was correlated
with funding source, also suggested clinical trials with
funding have more capacity to provide assurance for the
better quality of study design and reporting of RCTs.
There are some limitations to our study. First, we
didnt directly measure RCT methodological quality, because we did not verify the information from the authors
or their protocols. As important methodological criteria
may be omitted in published reports although adequately
carried out, the quality of reporting should be taken only
as an imperfect surrogate of true methodological quality.
Nevertheless published reports are the major source for
clinicians to judge the validity of the results, making the
quality of the report essential [20]. Second, to evaluate
the quality of reporting in RCTs quantitatively, according
to some rating methods published in previous studies
[20-23], we extracted major items, not all items, from the
CONSORT 2010 statement. Despite these limitations, we
think our results have good internal validity. In our survey,
the selection and abstraction processes were independently performed by two qualified assessors. Disagreements

Page 7 of 8

were uncommon, and they occurred often due to lack of

transparency or contradictory information in the reports.

Conclusions
Our findings show that the reporting quality of RCTs in
MET for PCOS is suboptimal especially in key methodological items. Regarding the crucial methodological issues
of blinding, allocation concealment, and analysis by ITT,
our results stress the need for researchers involved in
RCTs of MET for PCOS to improve the methodological
quality of their research through a strengthened international collaboration. Reporting of RCTs on MET for
PCOS should meet and keep up with the standards of the
CONSORT statement.
Additional file
Additional file 1: Database of RCTs in MET for PCOS.
Abbreviations
CC: clomiphene citrate; CENTRAL: Cochrane Central Register of Controlled
Trials; CONSORT: Consolidated Standards of Reporting Trials; ITT: intention-totreat; MET: metformin; PCOS: polycystic ovary syndrome; RCTs: randomized
controlled trials.
Competing interests
The authors declare that they have no competing interests.
Authors contributions
BYC: conception and design, data collection and analysis, manuscript writing
and final approval of the manuscript. JL: data collection and analysis, critical
revision and final approval of the manuscript. CZ: revising the manuscript
critically for important intellectual content and final approval of the
manuscript. MYL: conception and design, manuscript writing, final approval
of manuscript. All authors read and approved the final manuscript.
Acknowledgments
The authors would like to express sincere thanks to our colleagues, staff of
the First Peoples Hospital of Shunde, Foshan for their support. There was no
external funding for this project.
Received: 20 June 2013 Accepted: 3 April 2014
Published: 17 April 2014
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Cite this article as: Chen et al.: A retrospective survey of quality of
reporting on randomized controlled trials of metformin for polycystic
ovary syndrome. Trials 2014 15:128.

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