K.27.

Telaah Jurnal dan Critical Appraisal

Dr.dr.Nendyah Roestijawati, MKK
-Intan Rahmawati-

Dasar
 Pelayanan kesehatan rasional memerlukan pengetahuan tentang etiologi dan
patogenesis, diagnosis, terapi dan prognosis suatu penyakit
 RCT banyak menyediakan bukti berharga mengenai terapi dan intervensi lainnya
 Banyak pengetahuan klinis maupun kesehatan masyarakat diperoleh dari penelitian
observasional
 Sembilan dari 10 artikel penelitian yang dipublikasikan pada jurnal klinis
menggunakan penelitian observasional
 Laporan penelitian observasional seringkali kurang rinci dan kurang jelas untuk
dinilai kekuatan dan kelemahan penelitian
 Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)
 Tujuan untuk memperjelas apa yang direncanakan, dilakukan dan ditemukan pada
penelitian observasional
 Cohort, case control dan cross sectional
Tujuan
 Memberikan panduan melaporkan penelitian dengan baik
 Membantu penulis saat penulisan studi observasional analitik
 Membantu editor atau penelaah untuk pertimbangan publikasi
 Membantu pembaca mengkritisi artikel

Isi
 Judul artikel dan abstrak (item 1)
 Pengenalan (item2 dan 3)
 Metode (item 4-12)
 Hasil (item 13-17)
 Diskusi (item18-21)
 Informasi lain (item 22)
 18 item untuk semua studi
 Item 6,12,14,15 untuk disain tertentu
 Tanda bintang  infromasi terpisah
Title and abstrack
1. (a) Indicate the study’s design with a commonly used term in the title or the abstract
 Pembaca dapat dengan mudah mengidentifikasi disain penelitian yang digunakan
pada judul dan abstrak
 Menggunakan istilah disain yang umum
 ‘‘Leukaemia incidence among workers in the shoe and boot manufacturing industry: a
case-control study’’
1. (b) Provide in the abstract an informative and balanced summary of what was done
and what was found
 Abstrak menyajikan informasi penting yang memudahkan pembaca untuk mengerti
tentang penelitian dan memutuskan membaca artikel tsb
 Komponen khas : pertanyaan penelitian, deskripsi singkat metode dan hasil,
kesimpulan
 Ringkasan penting penelitian yang disajikan dalam artikel
 Hasil penting dalam bentuk angka termasuk jumlah subyek, estimasi asosiasi, ukuran
variabilitas seperti OR, CI, dll
  Tidak cukup hanya dinyatakan terdapat hubungan signifikan paparan dengan keluaran
Introduction
2. Background/rationale: Explain the scientific background and rationale for the
investigation being reported
 Gambaran apa yang diketahui mengenai topik penelitian dan kesenjangan dengan
pengetahuan saat ini  masalah
 Latar belakang menunjukkan penelitian dan review sistematik terkini yang terkait
3. Objectives: State specific objectives, including any prespecified hypotheses
 Menjelaskan secara rinci tujuan penelitian
 Dibuat secara spesifik populasi, paparan, keluaran dan parameter yang akan diukur
 Dapat dirumuskan dalam hipotesis yang spesifik atau pertanyaan penelitian
 Pada beberapa keadaan tujuan tidak spesifik, misal pada penelitian awal/dasar
 Mencerminkan niat peneliti
Method
4. Study design: Present key elements of study design early in the paper
 Di awal bagian metode atau akhir pendahuluan
 Dilengkapi penjelasan yang akan dilakukan
 Bagaimana dan kapan data akan dikumpulkan
 Bagian pertama dari metode disebutkan apakah laporan merupakan bagian dari
sebuah penelitan
 Secara singkat mengulang tujuan awal penelitian agar pembaca memahami konteks
penelitian dan kemungkinan keterbatasan data
Setting: Describe the setting, locations, and relevant dates, including periods of recruitment,
exposure, follow up, and data collection
 Diperlukan untuk menilai konteks dan generalisasi hasil studi
 Tempat dan sumber data: negara, kota, RS, layanan kesehatan, dll
 Waktu mulai pengumpulan data, bukan lamanya
Participants :
6 (a). Cohort study: Give the eligibility criteria, and the sources and methods of selection
of participants. Describe methods of follow-up
6 (a). Case-control study: Give the eligibility criteria, and the sources and methods of case
ascertainment and control selection. Give the rationale for the choice of cases and
controls
6 (a). Cross-sectional study: Give the eligibility criteria, and the sources and methods of
selection of participants.
COHORT
 Memudahkan pembaca untuk menerapkan hasil
 Batasan populasi dengan klinis, demografi, dll
 Bisa disajikan dalam kriteria inklusi dan eksklusi
 Penjelasan asal kelompok (populasi umum dari sebuah kota atau negara) dan metode
rekrutmen (rujukan, seleksi sendiri)
 Prosedur follow up apakah sama?
 Minimalisasi DO
 Kelengkapan definisi variabel (item 14)
CASE CONTROL
 Pemilihan kasus dan kontrol diperlukan untuk interpretasi hasil
 Metode seleksi berpengaruh pada validitas
 Kontrol mencerminkan dari populasi mana kasus berasal
 Kasus dari populasi umum, kontrol dari tetangga atau teman  matching paparan
intrinsik
  Kontrol penyakit lain  hospital based cases  mencerminkan populasi RS,
perbandingan yang baik, mudah rekruitmennya
 Kerugian : paparan merupakan faktor risiko penyakit pada kelompok kontrol 
beberapa penyakit
6 (b). Cohort study: For matched studies, give matching criteria and number of exposed and
unexposed
6 (b). Case-control study: For matched studies, give matching criteria and the number of
controls per case
 Umumnya pada case control
 Cohort : variabel konfounding
 Alasan pemilihan variabel matching
 Metode yang digunakan
7. Variables: Clearly define all outcomes, exposures, predictors, potential confounders, and
effect modifiers. Give diagnostic criteria, if applicable
 Definisi variabel yang akan dianalisis termasuk keluaran, paparan, prediktor,
konfounding, modifikasi
 Penyakit dibutuhkan deskripsi kriteria diagnostik yang adekuat
 Jika variabel banyak dapat digunakan tabel tambahan atau appendix
8. Data sources/measurement: For each variable of interest give sources of data and details of
methods of assessment (measurement). Describe comparability of assessment methods if
there is more than one group
 Menentukan validitas dan reliabilitas penelitian
 Uji validitas dan reliabilitas pengukuran (bila ada)
 Referensi yang digunakan
 Estimasi validitas dan reliabilitas  analisis sensitivitas (item 12e dan 17)
 Perbedaan perlakuan pada grup  bias
9. Bias: Describe any efforts to address potential sources of bias
 Penilaian kesalahan atau bias
 Estimasi besar bias
 Case control : bias informasi dikurangi dengan seleksi
 Program quality control bila menggunakan banyak observer
‘‘Detection bias could influence the association between Type 2 diabetes mellitus
(T2DM) and primary open-angle glaucoma (POAG) if women with T2DM were
under closer ophthalmic surveillance than women without this condition. We
compared the mean number of eye examinations reported by women with and without
diabetes. We also recalculated the relative risk for POAG with additional control for
covariates associated with more careful ocular surveillance (a self-report of cataract,
macular degeneration, number of eye examinations, and number of physical
examinations)’’
10. Study size: Explain how the study size was arrived at
 Perhitungan jumlah sampel
 Pertimbangan jumlah sampel
 Penelitian dihentikan setelah tercapai signifikansi
‘‘A survey of postnatal depression in the region had documented a prevalence of
19.8%. Assuming depression in mothers with normal weight children to be 20% and
an odds ratio of 3 for depression in mothers with a malnourished child we needed 72
case-control sets (one case to one control) with an 80% power and 5% significance’’
11. Quantitative variables: Explain how quantitative variables were handled in the
analyses. If applicable, describe which groupings were chosen, and why.
 bagaimana mengumpulkan dan menganalisis data kuantitatif paparan, variabel
modifikasi, konfounding
 penjelasan mengapa dan bagaimana pengelompokkan data, jumlah kategori, cut-
points, kategori mean, median
 Tabel : jumlah kasus, kontrol, orang berisiko, dll pada tiap kategori
 Data kontinyu : uji distribusi normal dan transformasi data
Statistical methods:
12 (a). Describe all statistical methods, including those used to control for
confounding
 analisis yang digunakan dan alasannya
 analisis variabel konfounding mengunakan analisis stratifikasi atau regresi
multivariable
 transformasi data, attributable risk
 software statistik yang digunakan
12 (b). Describe any methods used to examine subgroups and interactions
 analisis subgroup yang akan dilakukan dan yang mungkin muncul saat analisis data
 uji yang akan dilakukan bila asosiasi berbeda antar grup
‘‘The adjusted relative risk was calculated using the Mantel-Haenszel technique,
when evaluating if confounding by age or gender was present in the groups compared.
The 95%confidence interval (CI) was computed around the adjustedrelative risk,
using the variance according to Greenland and Robins and Robins et al.’’
12 (c). Explain how missing data were addressed
 jumlah nilai yang hilang untuk tiap variabel dan tiap tahapan
 alasan data missing dan subyek yang dieksklusi pada alur subyek
 metode data missing dan asumsinya
‘‘Our missing data analysis procedures used missing at random (MAR) assumptions.
We used the MICE (multivariate imputation by chained equations) method of
multiple multivariate imputation in STATA. We independently analysed 10 copies of
the data, each with missing values suitably imputed, in the multivariate logistic
regression analyses. We averaged estimates of the variables to give asingle mean
estimate and adjusted standard errors according to Rubin’s rules’’
12 (d). Cohort study: If applicable, describe how loss to follow-up was addressed
 life table, person time
 jumlah subyek DO dan strategi sensor
‘‘In treatment programmes with active follow-up, those lost to follow-up and those
followed-up at 1 year had similar baseline CD4 cell counts (median 115 cells per lL
and 123 cells per lL), whereas patients lost to follow-up in programmes with no active
follow-up procedures had considerably lower CD4 cell counts than those followed-up
(median 64 cells per lL and 123 cells per lL). (. . .) Treatment programmes with
passive follow-up were excluded fromsubsequent analyses’’
12 (d). Case-control study: If applicable, explain how matching of cases and controls
was addressed
 Jelaskan metode matching
 Crude OR
 Mantel-Haenszel
 Conditional logistic regression
 Jika dengan uji matching efek kecil  gunakan unmatch
‘‘We used McNemar’s test, paired t test, and conditional logistic regression analysis
to compare dementia patients with their matched controls for cardiovascular risk
 factors, the occurrence of spontaneous cerebral emboli, carotid disease, and venous to
arterial circulation shunt’’
12 (d). Cross-sectional study: If applicable, describe analytical methods taking
account of sampling strategy
 penjelasan metode yang digunakan untuk sampling
 SE atau CI
‘‘The standard errors (SE) were calculated using the Taylor expansion method to
estimate the sampling errors of estimators based on the complex sample design. (. . .)
The overall design effect for diastolic blood pressure was found to be 1.9 for men and
1.8 for women and, for systolic blood pressure, it was 1.9 for men and 2.0 for
women’’ [
12 (e). Describe any sensitivity analyses
 Digunakan untuk mengetahui apakah hasil tetap
 Identifikasi pengaruh variabel konfounding, bias seleksi atau bias informasi
 Tidak ditemukan asosiasi atau asosiasi kecil antara paparan dengan keluaran
‘‘Because we had a relatively higher proportion of ‘missing’ dead patients with
insufficient data (38/148¼25.7%) as compared to live patients (15/437¼3.4%) (. . .),
it is possible that this might have biased the results. We have, therefore, carried out a
sensitivity analysis. We have assumed that the proportion of women using oral
contraceptives in the study group applies to the whole (19.1% for dead, and 11.4% for
live patients), and then applied two extreme scenarios: either all the exposed missing
patients used second generation pills or they all used third-generation pills’’
Result
13. Participants
13 (a). Report the numbers of individuals at each stage of the study—e.g., numbers
potentially eligible, examined for eligibility, confirmed eligible, included in the study,
completing follow-up, and analysed
 Jumlah subyek tiap stage (multistage sampling)
 Dipisahkan kelompok kasus dan kontrol
13 (b). Give reasons for non-participation at each stage
 Penjelasan subyek dikeluarkan dari sampel
 Membantu pembaca untuk menilai apakah sampel representatif terhadap populasi atau
menimbulkan bias
 13 (c). Consider use of a flow diagram
 Descriptive data
14 (a). Give characteristics of study participants (e.g., demographic, clinical, social)
and information on exposures and potential confounders
 Membantu pembaca menentukan generalisasi hasil, validitas
 Data kontinyu : mean, SD, median, persentil25, persentil75
 Data kategori : angka atau proporsi
 Tidak diperlukan SE, CI, p
 Pada case control, potensial konfounding tidak boleh disimpulkan dari perbandingan
kasus dan kontrol
 14 (b). Indicate the number of participants with missing data for each variable of
interest
 Jumlah missing data paparan, konfounding, karakteristik lain
 Cohort : DO (dg alasan)  bias
 Gunakan tabel atau gambar

14 (c). Cohort study: Summarise follow-up time—e.g., average and total amount
 Lama follow-up
 mean dan atau median waktu follow-up
 minimum dan maximum atau percentil
outcame data
Cohort study: Report numbers of outcome events or summary measures over time
 Case-control study: Report numbers in each exposure category, or summary measures
of exposure

Cross-sectional study: Report numbers of outcome events or summary measures

16. Main results:

 16 (a). Give unadjusted estimates and, if applicable, confounder-adjusted estimates
and their precision (e.g.,95% confidence intervals). Make clear which confounders
were adjusted for and why they were included
 Adjusted dan unadjusted analysis
 Keterangan variabel konfounding, kriteria inklusi dan eksklusi variabel
 Strategi memilih variabel konfounding
 Tingkat signifikansi yang dipakai
 Tidak merekomendasikan memilih variabel konfounding berdasarkan uji statistik
16 (b). Report category boundaries when continuous variables were categorised

16 (c). If relevant, consider translating estimates of relative risk into absolute risk for
a meaningful time period
 metode yang digunakan utk menghitung
attributable risk
‘‘10 years’ use of HRT [hormone replacement therapy] is estimated to result in five
(95% CI 3–7) additional breast cancers per 1000 users of oestrogen-only preparations
and 19 (15–23) additional cancers per 1000 users of oestrogen progestagen
combinations’’
17. Other analyses: Report other analyses done—e.g., analyses of subgroups and
interactions, and sensitivity analyses
 Analisis yang akan dilakukan dan yang tidak
 Membantu pembaca memutuskan untuk mencari lebih jauh baik untuk keperluan
verifikasi atau menyanggah

Discussion
18. Key results: Summarize key results with reference to study objectives
 Memulai diskusi dengan hasil yang ditemukan
 Mengingatkan pembaca akan temuan utama dan memudahkan untuk menilai apakah
interpretasi dan implikasi didukung oleh hasil
19. Limitations: Discuss limitations of the study, taking into account sources of
potential bias or imprecision. Discuss both direction and magnitude of any potential
bias
 Identifikasi sumber bias, besar dan arahnya
 Besar sampel, pengukuran paparan, konfounding dan keluaran
 Membandingkan dengan hasil penelitian lain untuk validitas, generalisasi dan presisi
20. Interpretation: Give a cautious overall interpretation considering objectives,
limitations, multiplicity of analyses, results from similar studies, and other relevant
evidence
 Inti bagian diskusi adalah interpretasi hasil penelitian
 Sering terjadi Over-interpretation
 Pertimbangan bias misal DO, konfounding, analisis
 Konfounding lain yang tidak diukur sosial ekonomi (income, education, or
occupation)
21. Generalisability: Discuss the generalisability (external validity) of the study
results
 Apakah hasil penelitian dapat diaplikasikan pada keadaan yang lain (individu,
kelompok, populasi yang berbeda umur, jenis kelamin, etnis, derajat penyakit,
komorbid)
 Apakah paparan dapat dibandingkan, definisi keluaran relevan untuk kondisi lain
 Apakah data penelitian longitudinal yang lama masih relevan dengan kondisi
sekarang
 Apakah data layanan kesehatan suatu negara dapat diaplikasikan pada negara lain
 Tempat penelitian, karakteristik subyek, pengukuran paparan dan penilaian keluaran
Other information
22. Funding: Give the source of funding and the role of the funders for the present
study and, if applicable, for the original study on which the present article is based
pemerintah, profit, non profit
CONSORT
Title and abstract
Item 1a. Identification as a randomised trial in the title.
 “Smoking reduction with oral nicotine inhalers: double blind, randomised clnical trial
of efficacy and safety.”
Item 1b. Structured summary of trial design, methods, results, and conclusions
 Consort for abstract
 Clear, transparent, and sufficiently detailed
 accurately reflect what is included in the full journal article and should not include
information that does not appear in the body of the paper
 recommend the use of structured abstracts
Item 2a. Scientific background and explanation of rationale
 explain the scientific background and rationale
 include here the objectives of the trial
 Explanatory (possible influence of a drug on renal function) or pragmatic (guide
practice by comparing the benefits and harms of two treatments).
 report any evidence of the benefits and harms of active interventions included in a
trial and should suggest a plausible explanation for how the interventions might work,
if this is not obvious
Item 2b. Specific objectives or hypotheses
“In the current study we tested the hypothesis that a policy of active management of
nulliparous labour would: 1. reduce the rate of caesarean section, 2. reduce the rate of
prolonged labour; 3. not influence maternal satisfaction with the birth experience.”
Item 3a. Description of trial design (such as parallel, factorial) including allocation
ratio
“This was a multicenter, stratified (6 to 11 years and 12 to 17 years of age, with
imbalanced randomisation [2:1]), double-blind, placebo-controlled, parallel-group
study conducted in the United States (41 sites).
Item 3b. Important changes to methods after trial commencement (such as eligibility
criteria), with reasons
“Patients were randomly assigned to one of six parallel groups, initially in 1:1:1:1:1:1
ratio, to receive either one of five otamixaban … regimens … or an active control of
unfractionated heparin … an independent Data Monitoring Committee reviewed
unblinded data for patient safety; no interim analyses for efficacy or futility were
done. During the trial, this committee recommended thatthe group receiving the
lowest dose of otamixaban (N·NSH mg/kg/h) be discontinued because of clinical
evidence of inadequate anticoagulation. The protocol was immediately amended in
accordance with that recommendation, and participants were subsequently randomly
 assigned in 2:2:2:2:1 ratio to the remaining otamixaban and control groups,
respectively
Item 4a. Eligibility criteria for participants
 “Eligible participants were all adults aged 18 or over with HIV who met the eligibility
criteria for ntiretroviral therapy according to the Malawian national HIV treatment
guidelines (WHO clinical stage III or IV or any WHO stage with a CDT count
<GHN/mmS) and who were starting treatment with a BMI <18.5. Exclusion criteria
were pregnancy and lactation or participation in another supplementary feeding
programme”
Item 4b. Settings and locations where the data were collected
“The study took place at the antiretroviral therapy clinic of Queen Elizabeth Central
Hospital in Blantyre, Malawi, from January 2006 to April 2007. Blantyre is the major
commercial city of Malawi, with a population of 1.000.000 and an estimated HIV
prevalence of 27% in adults in 2004.”
Item 5. The interventions for each group with sufficient details to allow replication,
including how and when they were actually administered
 describe each intervention thoroughly, including control interventions
 drug name, dose, method of administration (such as oral, intravenous), timing and
duration of administration, conditions under which interventions are withheld, and
titration regimen if applicable
Item 6a. Completely defined pre-specified primary and secondary outcome measures,
including how and when they were assessed
“The primary endpoint with respect to efficacy in psoriasis was the proportion of
patients achieving a 75% improvement in psoriasis activity from baseline to 12 weeks
as measured by the PASI [psoriasis area and severity index] Additional analyses were
done on the percentage change in PASI scores and improvement in target psoriasis
lesions.”
Item 6b. Any changes to trial outcomes after the trial commenced, with reasons
 Authors should report all major changes to the protocol, including unplanned changes
to eligibility criteria, interventions, examinations, data collection, methods of analysis,
and outcomes
Item 7a. How sample size was determined
 “To detect a reduction in PHS (postoperative hospital stay) of 3 days (SD 5 days),
which is in agreement with the study of Lobo et al with a two-sided 5% significance
level and a power of 80%, a sample size of 50 patients per group was necessary, given
an anticipated dropout rate of 10%. To recruit this number of patients a 12-month
inclusion period was anticipated.”
Item 7b. When applicable, explanation of any interim analyses and stopping
guidelines
“Two interim analyses were performed during the trial. The levels of significance
maintained an overall P value of 0.05 and were calculated according to the O’Brien-
Fleming stopping boundaries. This final analysis used a Z score of 1.985 with an
associated P value of 0.0471.”
“An independent data and safety monitoring board periodically reviewed the efficacy
and safety data. Stopping rules were based on modified Haybittle-Peto boundaries of
4 SD in the first half of the study and 3 SD in the second half for efficacy data, and 3
SD in the first half of the study and 2 SD in the second half for safety data. Two
formal interim analyses of efficacy were performed when 50% and 75% of the
expected number of primary events had accrued; no correction of the reported P value
for these interim tests was performed.”
Item 8a. Method used to generate the random allocation sequence
“Independent pharmacists dispensed either active or placebo inhalers according to a
computer generated randomisation list.”
“For allocation of the participants, a computer-generated list of random numbers was
used.”
Item 8b. Type of randomisation; details of any restriction (such as blocking and block
size)
“Randomization sequence was created using Stata M.N (StataCorp, College Station,
TX) statistical software and was stratified by center with a 1:1 allocation using
random block sizes of 2, 4, and 6.”
“Participants were randomly assigned following simple randomization procedures
(computerized random numbers) to 1 of 2 treatment groups.”
Item 9. Mechanism used to implement the random allocation sequence (such as
sequentially numbered containers), describing any steps taken to conceal the
sequence until interventions were assigned
“The doxycycline and placebo were in capsule form and identical in appearance. They
were prepacked in bottles and consecutively numbered for each woman according to
the randomisation schedule. Each woman was assigned an order number and received
the capsules in the corresponding prepacked bottle.”
Item 10. Who generated the allocation sequence, who enrolled participants, and who
assigned participants to interventions
“Determination of whether a patient would be treated by streptomycin and bed-rest (S
case) or by bed-rest alone (C case) was made by reference to a statistical series based
on random sampling numbers drawn up for each sex at each centre by Professor
Bradford Hill; the details of the series were unknown to any of the investigators or to
the co-ordinator … After acceptance of a patient by the panel, and before admission
to the streptomycin centre, the appropriate numbered envelope was opened at the
central officer; the card inside told if the patient was to be an S or a C case, and this
information was then given to the medical officer of the centre.”
Item 11a. If done, who was blinded after assignment to interventions (for example,
participants, care providers, those assessing outcomes) and how
“Whereas patients and physicians allocated to the intervention group were aware of
the allocated arm, outcome assessors and data analysts were kept blinded to the
allocation.”
Item 11b. If relevant, description of the similarity of interventions
“Jamieson Laboratories Inc provided 500-mg immediate release niacin in a white,
oblong, bisect caplet. We independently confirmed caplet content using high
performance liquid chromatography… The placebo was matched to the study drug for
taste, color, and size, and contained microcrystalline cellulose, silicon dioxide,
dicalcium phosphate, magnesium stearate, and stearic acid.”
Item 12a. Statistical methods used to compare groups for primary and secondary
outcomes
“The primary endpoint was change in bodyweight during the 20 weeks of the study in
the intention-to treat population … Secondary efficacy endpoints included change in
waist circumference, systolic and diastolic blood pressure, prevalence of metabolic
syndrome … We used an analysis of covariance (ANCOVA) for the primary endpoint
and for secondary endpoints waist circumference, blood pressure, and patient-reported
outcome scores; this was supplemented by a repeated measures analysis. The
ANCOVA model included treatment, country, and sex as fixed effects, and
bodyweight at randomisation as covariate. We aimed to assess whether data provided
 evidence of superiority of each liraglutide dose to placebo (primary objective) and to
orlistat (secondary objective).”
Item 12b. Methods for additional analyses, such as subgroup analyses and adjusted
analyses
“Proportions of patients responding were compared between treatment groups with
the Mantel-Haenszel X2 test, adjusted for the stratification variable, methotrexate
use.”
Item 13. Participant flow (a diagram is strongly recommended)

Item 13a. For each group, the numbers of participants who were randomly assigned,
received intended treatment, and were analysed for the primary outcome

Item 13b. For each group, losses and exclusions after randomisation, together with
reasons
“There was only one protocol deviation, in a woman in the study group. She had an
abnormal pelvic measurement and was scheduled for elective caesarean section.
However, the attending obstetrician judged a trial of labour acceptable; caesarean
section was done when there was no progress in the first stage of labour.”
Item 14a. Dates defining the periods of recruitment and follow-up
“Age-eligible participants were recruited …from February 1993 to September 1994
… Participants attended clinic visits at the time of randomisation (baseline) and at -
6month intervals for 3 years.”
Item 14b. Why the trial ended or was stopped
 disclose factors extrinsic to the trial that aFected the decision to stop the trial, and who
made the decision to stop the trial, including reporting the role the funding agency
played in the deliberations and in the decision to stop the trial
 Item 15. A table showing baseline demographic and clinical characteristics for each
group

Item 16. For each group, number of participants (denominator) included in each
analysis and whether the analysis was by original assigned groups
“One patient in the alendronate group was lost to follow up; thus data from 31
patients were available for the intention-to-treat analysis. Five patients were
considered protocol violators … consequently 26 patients remained for the
perprotocol analyses.”
Item 17a. For each primary and secondary outcome, results for each group, and the
estimated effect size and its precision (such as 95% confidence interval)

Item 17b. For binary outcomes, presentation of both absolute and relative effect sizes
is recommended

Item 18. Results of any other analyses performed, including subgroup analyses and
adjusted analyses, distinguishing prespecified
from exploratory
 Multiple analyses of the same data create a risk for false positive findings
 Authors should resist the temptation to perform many subgroup analyses
Item 19. All important harms or unintended effects in each group
CONSORT for harms
“The proportion of patients experiencing any adverse event was similar between the
rBPIG8 [recombinant bactericidal/permeability-increasing protein] and placebo
 groups: 168 (88.4%) of 190 and 180 (88.7%) of 203, respectively, and it was lower in
patients treated with rBPIG8 than in those treated with placebo for 88 of 8G body
systems … the proportion of patients experiencing a severe adverse event, as judged
by the investigators, was numerically lower in the rBPIG8 group than the placebo
group: ….. of GNS patients, respectively. There were only three serious adverse
events reported as drug-related and they all occurred in the placebo group.”
Item 20. Trial limitations, addressing sources of potential bias, imprecision, and, if
relevant, multiplicity of analyses
“The preponderance of male patients (85%) is a limitation of our study … We used
bare-metal stents, since drug-eluting stents were not available until late during
accrual. Although the latter factor may be perceived as a limitation, published data
indicate no benefit (either shortterm or long-term) with respect to death and
myocardial infarction in patients with stable coronary artery disease who receive
drug-eluting stents, as compared with those who receive bare-metal stents.”
Item 21. Generalisability (external validity, applicability) of the trial findings
“As the intervention was implemented for both sexes, all ages, all types of sports, and
at different levels of sports, the results indicate that the entire range of athletes, from
young elite to intermediate and recreational senior athletes, would benefit from using
the presented training programme for the prevention of recurrences of ankle sprain.
By including non-medically treated and medically treated athletes, we covered a
broad spectrum of injury severity. This suggests that the present training programme
can be implemented in the treatment of all athletes. Furthermore, as it is reasonable to
assume that ankle sprains not related to sports are comparable with those in sports, the
programme could benefit the general population.”
Item 22. Interpretation consistent with results, balancing benefits and harms, and
considering other relevant evidence
 “Studies published before 1990 suggested that prophylactic immunotherapy also
reduced nosocomial infections in very-low-birth-weight infants. However, these
studies enrolled small numbers of patients; employed varied designs, preparations,
and doses; and included diverse study populations. In this large multicenter,
randomised controlled trial, the repeated prophylactic administration of intravenous
immune globulin failed to reduce the incidence of nosocomial infections significantly
in premature infants weighing 501 to 1500 g at birth.”
Item 23. Registration number and name of trial registry
“The trial is registered at ClinicalTrials.gov, number NCT00244842.”
Item 24. Where the full trial protocol can be accessed, if available
“Full details of the trial protocol can be found in the Supplementary Appendix,
available with the full text of this article at www.nejm.org.”
Item 25. Sources of funding and other support (such as supply of drugs), role of
funders
“This study was funded by GlaxoSmithKline Pharmaceuticals. GlaxoSmithKline was
involved in the design and conduct of the study and provided logistical support during
the trial. Employees of the sponsor worked with the investigators to prepare the
statistical analysis plan, but the analyses were performed by the University of Utah.
The manuscript was prepared by Dr Shaddy and the steering committee members.
GlaxoSmithKline was permitted to review the manuscript and suggest changes, but
the final decision on content was exclusively retained by the authors.”