5. 構成,RCTでも雑誌に依存
5
Ann Intern Med[1]
• ⽅法の概要 (Design Overview)
• セッティングと調査参加者
(Setting and Participants)
• 無作為化と介⼊ (Randomization
and Interventions)
• アウトカムと追跡 (Outcomes and
Follow-up)
• 統計解析 (Statistical Analysis)
• 資⾦源の役割 (Role of Funding
Source)
JAMA[2]
• 研究法 (Study Design)
• 調査参加者 (Participants)
• 無作為化と割り付け
(Randomization and Allocation)
• 介⼊ (Intervention)
• アウトカム (Study Outcome)
• 統計 (Statistics)
[1] Pianko S et al: Ann Intern Med. 2015 Dec 1;163(11):809-17.
[2] Faisy C et al: JAMA. 2016 Feb 2;315(5):480-8.
6. 時制,基本は過去形,受動態
試験デザイン
» This phase 2, multicenter, randomized, open-label study was
conducted from June 2013 (when the first patient was
enrolled) to August 2014 (when the last patient completed
follow-up).[1]
調査対象
» Patients older than 18 years with a history of COPD according
to the American Thoracic Society criteria <中略> were
enrolled if they required invasive ventilation via an
intubation or tracheotomy tube and were evaluated within 24
hours after its onset.[2]
6
[1] Pianko S et al: Ann Intern Med. 2015 Dec 1;163(11):809-17.
[2] Faisy C et al: JAMA. 2016 Feb 2;315(5):480-8.
7. 時制,現在形は限定的に
7
研究計画書
» The trial protocol and statistical analysis plan are available in
Supplement 1.[1]
流れ図
» The study schematic is shown in Figure 1.[2]
既存の尺度
» The GAD Scale 7 Item is a self-reported measure of DSM-IV
symptoms of GAD[generalized anxiety disorder]. <中略> It
has good internal consistency (α = 0.89-0.92) and test-retest
reliability (intraclass correlation coefficient = 0.83).[3]
[1] Chawes BL et al: JAMA. 2016 Jan 26;315(4):353-61.
[2] Marr KA et al: Ann Intern Med. 2015 Jan 20;162(2):81-9.
[3] Brenes GA et al: JAMA Psychiatry. 2015 Oct;72(10):1012-20.
8. 可読性のため,1⽂に2アクション
1⽂1アクション
» A first postal invitation to participate in the survey was sent
to 26 practices in South Yorkshire.
» A total of five practices indicated their willingness to
participate.
1⽂2アクション
» Following a first postal invitation to participate sent to 26
practices in South Yorkshire, five responded positively.
8Wallwork A: English for Writing Research Papers. Springer. 2011
9. 単語数の削減法,①前提知識を除外
混合モデルの利点
» For the primary and secondary analyses, we fit linear mixed
models by using an intention-to-treat approach (ref). <中略>
A benefit of using a mixed-model framework for longitudinal
analysis is that all available data are used.[1]
混合モデルの利点は⾃明
» A mixed linear model (MLM) analysis of covariance was
used to model scores at each measurement occasion with
subject treated as a random effect, and the interaction
between measurement occasion and treatment group in
order to test the central hypothesis of differential treatment
response (compared with pre-treatment) between treatment
modalities.[2]
9
[1] Allen KD et al: Ann Intern Med. 2010 Nov 2;153(9):570-9.
[2] Spence J et al: J Affect Disord. 2014 Jun;162:73-80.
10. 単語数の削減法,②詳細を引⽤
研究計画書
» Details of the study protocol have been reported elsewhere
(ref).[1]
割り付け法 (最⼩化法)
» Randomization was stratified by week of gestation, trial site,
and inherited thrombophilia using the minimization method
described by Pocock and Simon (ref).[2]
介⼊法
» The development process and content of the iDecide program
have been described in detail elsewhere (ref).[3]
10
[1] Yancy WS Jr et al: Ann Intern Med. 2015 Jun 16;162(12):805-14.
[2] Schleussner E et al: Ann Intern Med. 2015 May 5;162(9):601-9.
[3] Heisler M et al: Ann Intern Med. 2014 Nov 18;161(10 Suppl):S13-22.
11. 単語数の削減法,③図表付録を参照
適格基準
» Full eligibility criteria are listed in the study protocol
(Supplement, available at www.annals.org).[1]
統計モデルの変数
» A separate model was estimated for each of the 8 outcome
factors, listed in Table 3.[2]
» The propensity score was estimated with logistic regression,
with all variables listed in tables 1 and 2 and additionally, all
estimable two way interactions between demographic and
healthcare use variables, included as predictors.[3]
11
[1] Pianko S et al: Ann Intern Med. 2015 Dec 1;163(11):809-17
[2] Bergström J et al: BMC Psychiatry. 2010 Jul 2;10:54.
[3] Svanström H et al: BMJ. 2012 Nov 8;345:e7176.
12. 表現法,⽅法選択の意図・合理性
to
» Univariate and multivariate Cox proportional hazards regression
analyses of baseline patient characteristics were done to identify
independent predictors of death by treatment group (Supplement
2).[1]
» To validate this assumption of independence, a sensitivity analysis
was performed with successive increasing interval requirements
between cases of CDI [Clostridium Difficile Infection].[2]
chosen
» These protocols were chosen because they are widely used and
were either developed for delivery in a group format or have been
previously utilized in trials of group anxiety treatment.[3]
12
[1] Marr KA et al: Ann Intern Med. 2015 Jan 20;162(2):81-9.
[2] Nylund CM et al: J Pediatr. 2014 Nov;165(5):979-84.
[3] Norton PJ, Barrera TL: Depress Anxiety. 2012 Oct;29(10):874-82.
13. 表現法,⽅法によって〜できる
allow/enable/permit + someone to do
» This model enabled us to adjust variance estimates for the
correlation of multiple blood glucose measurements on the
same individual over time.[1]
allow/enable/permit + 名詞
» This approach allowed comparison of the incidence of
adverse events during periods of use of clopidogrel plus PPI
[proton pump inhibitor] vs use of clopidogrel without PPI.[2]
13
[1] Kennedy L et al: Diabetes Care. 2006 Jan;29(1):1-8.
[2] Ho PM et al: JAMA. 2009 Mar 4;301(9):937-44.
14. 表現法,⽅法選択の結果
thereby/thus + –ing
» The primary end point was a composite outcome consisting
of CMV [cytomegalovirus] disease, invasive bacterial or
fungal infections, or death (whichever occurred first), thereby
assessing the net effect of the strategy, including
consequences of neutropenia (ref).[1]
» With this technique, each admission in which acidsuppressive
medication was ordered was matched to the admission with
the closest propensity score in which acidsuppressive
medication was not ordered, thus addressing confounding
by indication.[2]
14
[1] Boeckh M et al: Ann Intern Med. 2015 Jan 6;162(1):1-10.
[2] Herzig SJ et al: JAMA. 2009 May 27;301(20):2120-8
15. 発表構成
⽅法 (Chapter 15)
結果 (Chapter 16)
考察 (Chapter 17)
結論 (Chapter 18)
15Wallwork A: English for Writing Research Papers. Springer. 2011
18. 構成事例,①Study Population
» The study flow diagram is shown in Figure 1. Table 1 shows
balanced clinical characteristics between the study groups.
18Boeckh M et al: Ann Intern Med. 2015 Jan 6;162(1):1-10.
19. 構成事例,②Primary End Point
» There were no statistically significant differences between
the groups for the composite end point (death or CMV
disease or other serious invasive infections by 270 days after
HCT) or its individual components (Figure 2 and Tables 1
and 2).
19Boeckh M et al: Ann Intern Med. 2015 Jan 6;162(1):1-10.
20. 構成事例,③Secondary Efficacy End Points
» The cumulative incidence of initiation of preemptive
therapy (CMV DNA level >1000 copies/mL of plasma or
increasing CMV DNA levels of >5 times the baseline level),
any CMV DNA detection, and any PCR positivity and CMV
DNA level greater than 10 000 copies/mL are shown in
Tables 2 and 3 and Figure 3.
20Boeckh M et al: Ann Intern Med. 2015 Jan 6;162(1):1-10.
21. 構成事例,④Safety End Points
» The number of patients with adverse events (AEs) and
serious AEs (Appendix Table 2, available at www.annals.org)
did not differ.
21Boeckh M et al: Ann Intern Med. 2015 Jan 6;162(1):1-10.
23. 統合失調症に対する抗精神病薬の減薬法
23
P : 統合失調症における抗精神病薬の多剤使
⽤者
I : 減薬プログラム
C : 通常診療
O : 精神症状と⽣活の質
T : 介⼊終了12週時点
主要評価項⽬に差が認められない
(⾮劣性試験)
Yamanouchi, Y, Sukegawa, T, Inagaki, A et al: Int J Neuropsychopharmacol 2015; 18.
26. 基本は,過去形・⾮⼈称型,①量的変数
» The least squares mean change in bilateral endoscopic
nasal polyp score between baseline and week 16 was −0.3
(95% CI, −1.0 to 0.4) in the placebo plus mometasone furoate
nasal spray group and −1.9 (95% CI, −2.5 to −1.2) in the
dupilumab plus mometasone furoate nasal spray group (least
squares mean difference, −1.6 [95% CI, −2.4 to −0.7], P
< .001; Table 2 and Figure 2A).
26Bachert C et al: JAMA. 2016 Feb 2;315(5):469-79.
27. 基本は,過去形・⾮⼈称型,②量的変数
» Mean changes in physical function for the surgery and PT
groups were 22.4 (95% CI, 16.9 to 27.9) and 19.2 (CI, 13.6 to
24.8), respectively. The ITT analyses revealed no difference
between the surgery and PT groups at all points of follow-up
(P > 0.50), including the 2-year primary end point (adjusted
mean difference, 0.85 [CI, -7.9 to 9.6]) (Table 2 and Figure
2).[2]
27Delitto A et al: Ann Intern Med. 2015 Apr 7;162(7):465-73.
28. 基本は,過去形・⾮⼈称型,③質的変数
» In the primary analysis, mortality at 6 weeks in the mITT
population was 19.5% (26 of 135) for combination treatment
and 27.8% (39 of 142) for monotherapy (difference, -8.2
percentage points [95% CI,-19.0 to 1.5]; 2-sided P = 0.087).
28Marr KA et al: Ann Intern Med. 2015 Jan 20;162(2):81-9.
29. 基本は,過去形・⾮⼈称型,④質的変数
» The proportion of women who achieved 25-hydroxyvitamin
D levels higher than 30 ng/mL in the 4400-IU group (74.9%)
was greater than that in the 400-IU group (34.0%;
difference, 40.9%, 95% CI, 34.2%-47.5%; P < .001) (Table 3).
[2]
29Litonjua AA et al: JAMA. 2016 Jan 26;315(4):362-70.
30. 統計量,①パーセンテージ,標準偏差
パーセンテージの有効桁数
n ≥ 200 ➡ xx.x%
n < 200 ➡ xx%
標準偏差の表記
× mean ± SD
○ mean (SD)
30
Information for Authors : General statistical guidance
(http://annals.org/SS/AuthorInformationStatisticsOnly.aspx)
31. 統計量,②標準誤差,傾向
標準誤差より信頼区間
× standard errors
○ confidence intervals
傾向の含意 (trend)
× 有意傾向
○ 傾向性検定
31
Information for Authors : General statistical guidance
(http://annals.org/SS/AuthorInformationStatisticsOnly.aspx)
32. 発表構成
⽅法 (Chapter 15)
結果 (Chapter 16)
考察 (Chapter 17)
結論 (Chapter 18)
32Wallwork A: English for Writing Research Papers. Springer. 2011
33. 考察のチェックポイント
知識の差 (knowledge gap) が埋まったかを明瞭に
新規性と重要を説明
結果を解釈
バランス感覚のある議論に
推論と事実を明瞭に区分
本研究と先⾏研究の結果を明瞭に区分
都合の悪い先⾏研究も参照
33Wallwork A: English for Writing Research Papers. Springer. 2011
34. 構成
①主要な結果の要約
②先⾏研究との⽐較
③可能性のある説明
④本研究の限界 (と強み)
⑤臨床的・研究的⽰唆
34
[1] Moher D et al: BMJ. 2010 Mar 23;340:c869
[2] Vandenbroucke JP et al: PLoS Med. 2007 Oct 16;4(10):e297
35. 構成事例,①主要な結果の要約
» In this large cohort study of metabolically healthy Korean
adults, being overweight or obese was associated with
increased CKD [chronic kidney disease] risk compared with
being normal weight. The association between MHO
[metabolically healthy obese] and CKD was consistently
seen in all prespecified clinical subgroups, including
participants without low-grade inflammation or fatty liver.
35Chang Y et al: Ann Intern Med. 2016 Mar 1;164(5):305-12.
36. 構成事例,②先⾏研究との⽐較
» A previous study in a sample of Japanese men and
women found no association between MHO [metabolically
healthy obese] and CKD [chronic kidney disease] (ref), but
this study defined metabolically healthy participants as
those with fewer than 2 metabolic abnormalities. In
contrast, we defined metabolically healthy participants as
those without any abnormality, including no increase in
HOMA-IR [homeostasis model assessment of insulin
resistance] score.
36Chang Y et al: Ann Intern Med. 2016 Mar 1;164(5):305-12.
37. 構成事例,③可能性のある説明
» The mechanisms whereby obesity contributed to CKD
[chronic kidney disease] remain incompletely elucidated.
In our study, the association between MHO [metabolically
healthy obese] and CKD was evident even after adjustment
for metabolic components, <後略>. Potential mechanisms
directly linking obesity to kidney damage independent of
metabolic risk factors include hemodynamic changes,
oxidative stress, and hormonal effects (ref).
37Chang Y et al: Ann Intern Med. 2016 Mar 1;164(5):305-12.
38. 構成事例,④本研究の限界 (と強み)
限界
» Several limitations of our study need to be considered.
First, we used BMI [body mass index] as a marker of
obesity, but it is an imperfect measure of adiposity and
does not distinguish differences in adipose tissue
distribution.
強み
» Our study also had several strengths, including the large
sample size and the availability of detailed information
on multiple laboratory variables, which allowed us to study
many participants even after excluding those with metabolic
abnormalities or insulin resistance.
38Chang Y et al: Ann Intern Med. 2016 Mar 1;164(5):305-12.
39. 構成事例,⑤臨床的・研究的⽰唆
» In conclusion, being overweight or obese was associated with
increased CKD [chronic kidney disease] incidence in
metabolically healthy young and middle-aged participants.
These findings indicate that MHO [metabolically healthy
obese] is not a harmless condition and that the obese
phenotype, regardless of metabolic abnormalities, can
adversely affect renal function. Therefore, physicians
should address the increased CKD risk in MHO persons
and counsel them about healthy weight and lifestyle.
39Chang Y et al: Ann Intern Med. 2016 Mar 1;164(5):305-12.
40. 先⾏研究との⽐較,①新規系統的レビュー
» To scour the literature for similar trials and meta-
analyses, we searched PubMed and combined the terms
“heparin” with “recurrent (early) miscarriages(s)” in November
2014. We found 4 randomized, controlled trials similar to
ours, which were also included in a Cochrane analysis
(ref). Two trials showed the efficacy of LMWH [low-molecular-
weight heparin]. Each required at least 3 consecutive
miscarriages for eligibility. But the low miscarriage rate in 1
trial (ref), especially in the intervention group (5% [9 of 170
women]), seems questionable.
40Schleussner E et al: Ann Intern Med. 2015 May 5;162(9):601-9.
41. 先⾏研究との⽐較,②通常のレビュー
» We found no difference between CCTA [coronary computed
tomography angiography] and MPI [radionuclide stress
myocardial perfusion imaging] in cardiac catheterizations
within 1 year (15% versus 16%). This differs with research
derived from a retrospective review of Medicare claims
data (ref), a meta-analysis of randomized trials in low-risk
emergency department patients (ref) and a large
multicenter trial of outpatients (ref), all of which showed
increased catheterizations after CCTA.
41Levsky JM et al: Ann Intern Med. 2015 Aug 4;163(3):174-83.
42. 限界,①情報バイアス
» However, the lack of information on over-the-counter
NSAID use may have introduced a conservative
misclassification bias and attenuated the risk estimates.[1]
» First, the study database was limited to claims data to
assess fracture outcomes and may have misclassified
some fractures. However, we minimized the potential for
misclassification (information bias) by studying fractures at
the hip, humerus, and radius or ulna with validated fracture
codes (diagnostic and procedural codes) that have an
estimated sensitivity of at least 90% (ref). There is also no
reason to believe that differential misclassification of
fractures between treatment agents occurred.[2]
42
[1] Friis S et al: Ann Intern Med. 2015 Sep 1;163(5):347-55.
[2] Cadarette SM et al: Ann Intern Med. 2008 May 6;148(9):637-46.
43. 限界,②選択バイアス
» Another potential limitation is selection bias by incomplete
and potentially differential participation rates of eligible
case patients and control participants. <中略> Because
associations with colonoscopy were slightly stronger in older
patients and those with more advanced disease,
underrepresentation of these patients may have led to some
underestimation of overall risk reduction.[1]
» In addition, our results may be susceptible to response bias if
physicians with a greater interest or experience in cancer
survivorship were more likely to have responded to the
survey. However, there were no statistically significant
differences between respondents and nonrespondents in
terms of sex, age, and geographic location.[2]
43
[1] Brenner H et al: Ann Intern Med. 2011 Jan 4;154(1):22-30.
[2] Suh E et al: Ann Intern Med. 2014 Jan 7;160(1):11-7.
44. 限界,③交絡
» We detected a strong association between opioid dosage
after a nonfatal overdose and risk for repeated overdose;
however, we cannot conclude that the relationship is
causal. Claims data are limited in availability of
covariates, and unmeasured confounding is probably
substantial. Important contextual factors missing from
claims data include the medical and social circumstances
surrounding the overdose, quality and degree of counseling,
availability of substance abuse treatment, referral to specialist
care, and patients' desire to change.
44Larochelle MR et al: Ann Intern Med. 2016 Jan 5;164(1):1-9.
45. 限界,④不確実性
» The main limitation of the study is a reduced statistical
power to detect an effect on the primary end point of
persistent wheeze.[1]
» Fifth, nonsignificant trends associated with relatively wide
CIs do not necessarily indicate the true absence of
trends.[2]
45
[1] Chawes BL et al: JAMA. 2016 Jan 26;315(4):353-61.
[2] Silverberg MJ et al: Ann Intern Med. 2015 Oct 6;163(7):507-18.
46. 限界,⑤測定の信頼性・妥当性
» Second, results are dependent on EHR [electronic health
records] and billing data, which are imperfect for
performance measurement—although in the present
context they have demonstrated validity (ref).[1]
» Fifth, information on smoking, alcohol use, physical activity,
and medical history was obtained via a self-administered
structured questionnaire used in health checkup
programs in Korea as part of the National Health
Insurance Program, and measurement error in these
variables may have resulted in some degree of residual
confounding.[2]
46
[1] Meeker D et al: JAMA. 2016 Feb 9;315(6):562-70.
[2] Chang Y et al: Ann Intern Med. 2016 Mar 1;164(5):305-12.
47. ⼀般化可能性
可能性
» Fourth, the inclusion of MSM [men who have sex with men]
from 4 sites across the United States allows our findings to
be generalizable to MSM in large cities across the United
States.[1]
限界
» Foremost, this was a single-center study, and institution-
specific factors may limit generalizability.[2]
47
[1] Falade-Nwulia O et al: Ann Intern Med. 2015 Nov 3;163(9):673-80.
[2] Levsky JM et al: Ann Intern Med. 2015 Aug 4;163(3):174-83.
48. 発表構成
⽅法 (Chapter 15)
結果 (Chapter 16)
考察 (Chapter 17)
結論 (Chapter 18)
48Wallwork A: English for Writing Research Papers. Springer. 2011
49. 結論のチェックポイント
⼗分に短く (< 200 words)
考察と独⽴していない場合,強調 (In conclusion)
⽅法の記述は1⾏,あるいはゼロ
他の節のコピペを回避
興味・関⼼の⾼い結論に
実現可能性のある臨床的・政策的⽰唆に
49Wallwork A: English for Writing Research Papers. Springer. 2011
51. 構成事例①
①最も重要な結果
» In conclusion, the use of an early invasive treatment
strategy among patients hospitalized with a first ACS
[acute coronary syndromes] was associated with a
decreased risk for short-term adverse cardiac events
compared with a conservative invasive approach.
⑥臨床的重要性
» Our findings confirm those of several randomized clinical
trials. Thus, health care providers are encouraged to
adhere to the time frames stated in international
guidelines and fast-track protocols.
51Hansen KW et al: Ann Intern Med. 2015 Nov 17;163(10):737-46.
52. 構成事例②
①最も重要な結果
» In this secondary analysis of ALLHAT, higher VVV [visit-to-visit
variability] of SBP [systolic blood pressure] and DBP [diastolic
blood pressure] were associated with an increased risk for CVD
[cardiovascular disease] and all-cause mortality.
②結果の重要性に関する最終判断
» The current study adds to the growing body of evidence on the
prognostic importance of VVV of BP as a CVD risk factor.
⑤今後の研究の課題
» Future studies are needed to identify the mechanisms
underlying the association between high VVV of BP and the risk
for CVD and mortality and to determine whether lowering VVV of
BP reduces this risk.
52Muntner P et al: Ann Intern Med. 2015 Sep 1;163(5):329-38.
53. 本⽂と要旨の結論部,①既読か初出か
本⽂の結論部,既読を想定
» In conclusion, the use of an early invasive treatment strategy
among patients hospitalized with a first ACS [acute coronary
syndromes] was associated with a decreased risk for short-term
adverse cardiac events compared with a conservative invasive
approach. Our findings confirm those of several randomized
clinical trials. Thus, health care providers are encouraged to adhere
to the time frames stated in international guidelines and fast-
track protocols.
要旨の結論部,初出を想定
» In this real-world cohort of patients with a first hospitalization for
an ACS [acute coronary syndromes], the use of an early invasive
treatment strategy was associated with a lower risk for cardiac
death and rehospitalization for MI [myocardial infarction]
compared with a conservative invasive approach.
53Hansen KW et al: Ann Intern Med. 2015 Nov 17;163(10):737-46.
54. 本⽂と要旨の結論部,②ほぼコピー
本⽂の結論部
» Among adults motivated to quit smoking, 12 weeks of open-label
treatment with nicotine patch, varenicline, or C-NRT produced no
significant differences in biochemically confirmed rates of smoking
abstinence at 26 or 52 weeks. The results raise questions about the
current relative effectiveness of intense smoking cessation
pharmacotherapies.
要旨の結論⽂
» Among adults motivated to quit smoking, 12 weeks of open-label
treatment with nicotine patch, varenicline, or C-NRT produced no
significant differences in biochemically confirmed rates of smoking
abstinence at 26 weeks. The results raise questions about the
relative effectiveness of intense smoking pharmacotherapies.
54Baker TB et al: JAMA. 2016 Jan 26;315(4):371-9.