10. 研究疑問の定式化の事例
10
P : 12~18歳の慢性疲労症候群の患者を対象に,
I : インターネット⽀援型認知⾏動療法を受けた⼈は,
C : 通常の理学療法⼠による介⼊を受けた⼈と⽐べて,
O : 過去12⽇間における授業の完全出席率が⾼いか
T : 治療開始6か⽉時点
Nijhof SL et al: Lancet. 2012 Apr 14;379(9824):1412-8.
21. 標題から研究疑問の定式化
A Home-Based Intervention to Reduce Depressive Symptoms and Improve
Quality of Life in Older African Americans: A Randomized Trial
24
P : ⾼齢者のアフリカ系アメリカ⼈
I : ⾃宅における介⼊
C : ︖
O : うつ病の重症度と⽣活の質 (主要評価項⽬が2つ︖)
T : ︖
Gitlin LN et al: Ann Intern Med. 2013 Aug 20;159(4):243-52
22. 要旨から患者-介⼊-⽐較対象の精緻化
Patients: African Americans aged 55 years or older with depressive
symptoms.
Intervention: A multicomponent, home-based intervention delivered by
social workers or a wait-list control group that received the intervention at
4 months.
25
旧 新
P : ⾼齢者のアフリカ系ア
メリカ⼈
55歳以上のうつ症状を有するアフ
リカ系アメリカ⼈
I : ⾃宅における介⼊
ソーシャルワーカーによる⾃宅に
おける複合的介⼊
C : ︖ 4か⽉間の治療待機群
Gitlin LN et al: Ann Intern Med. 2013 Aug 20;159(4):243-52
23. 要旨からアウトカム-時間の精緻化
Measurements: Self-reported depression severity at 4 months (primary
outcome) and depression knowledge, quality of life, behavioral activation,
anxiety, function, and remission at 4 and 8 months.
26
旧 新
O : うつ病の重症度と⽣活
の質 (主要評価項⽬が2
つ︖)
⾃⼰記⼊式のうつ病の重症度
T : ︖ 4か⽉時点
Gitlin LN et al: Ann Intern Med. 2013 Aug 20;159(4):243-52
24. ⽅法からアウトカムの精緻化
Outcomes and Follow-up
The primary outcome was severity of depressive symptoms assessed with
the PHQ-9, a brief, psychometrically valid, 9-item self-report measure.
Higher scores indicated greater severity (Cronbach 0.769 for sample).
27
旧 新
O : ⾃⼰記⼊式のうつ病の
重症度
⾃⼰記⼊式尺度PHQ-9のうつ病の
重症度
Gitlin LN et al: Ann Intern Med. 2013 Aug 20;159(4):243-52
25. ⽅法からアウトカムの精緻化
Statistical Analysis
The primary treatment effect was the between group difference in change
from baseline to 4 months, estimated using the ESTIMATE statement in
SAS.
28
旧 新
O : ⾃⼰記⼊式尺度PHQ-9
のうつ病の重症度
⾃⼰記⼊式尺度PHQ-9のうつ病の
重症度 (4か⽉時点と基準時の変化
量の群間差)
Gitlin LN et al: Ann Intern Med. 2013 Aug 20;159(4):243-52
26. 研究疑問のまとめ
29
P : 55歳以上のうつ症状を有するアフリカ系アメリカ⼈
I : ソーシャルワーカーによる⾃宅における複合的介⼊
C : 4か⽉間の治療待機群
O : ⾃⼰記⼊式尺度PHQ-9のうつ病の重症度 (4か⽉時点
と基準時の変化量の群間差)
T : 4か⽉時点
Gitlin LN et al: Ann Intern Med. 2013 Aug 20;159(4):243-52
27. 図表 and/or 要旨 and/or 結果から
主要評価項⽬の群間差を把握
30
治療群は6.9点改善
(4か⽉時点と基準時の変化量)
対照群は3.8点改善
(4か⽉時点と基準時の変化量)
変化量の群間差は有意に
治療群が3.0点改善
Gitlin LN et al: Ann Intern Med. 2013 Aug 20;159(4):243-52
28. 考察の最後 and/or 要旨から
結論の⼀⽂と研究疑問との整合性の把握
研究疑問の整合性
✅ ⽣活の質は,主要評価項⽬ではない
✅ 主要評価項⽬は変化量の群間差なので,パーセンテージを暗
⽰する「⼤部分」の表現は不思議
31Gitlin LN et al: Ann Intern Med. 2013 Aug 20;159(4):243-52
結論
ソーシャルワーカーによる⾃宅における介⼊は,⼤部分のアフ
リカ系アメリカ⼈において,うつ病の重症度を下げ,⽣活の質
を改善できるだろう
Conclusion: A home-based intervention delivered by social workers could
reduce depressive symptoms and enhance quality of life in most older African
Americans.
46. 有意な結果の信頼区間の解釈
51
0
C is better E is better
「統計的に有意」
と判断する限界値
「臨床的に有意」
と判断する限界値
決定的に差が認められる
結果は決定的ではなく
追試が必要
Guyatt et al: Users’ guide to the medical literature (3rd ed). JAMAevidence. 2015.
48. 有意でない結果の信頼区間の解釈
53
0
C is better E is better
「統計的に有意」
と判断する限界値
「臨床的に有意」
と判断する限界値
決定的に差が
認められない
結果は決定的ではなく
追試が必要
Guyatt et al: Users’ guide to the medical literature (3rd ed). JAMAevidence. 2015.
72. 乱数⽣成の評価基準例
‘High risk’ of bias
介⼊の利⽤可能性により割り付け (allocated by availability of the
intervention)
患者の好みにより割り付け (allocation by preference of the participants)
‘Low risk’ of bias
コンピュータによる乱数⽣成 (using a computer random number generator)
最⼩化法の使⽤ (using minimization methods)
‘Unclear risk’ of bias
無作為に割り付け
(patients were randomly allocated)
78Chapter 8: Assessing risk of bias in included studies (http://www.cochrane.org/handbook)
73. 乱数⽣成の評価事例
研究 評価 判断根拠の記述
Hayward
2000[1]
High ”Twelve subjects were recruited for each randomisation,
with 6 subjects randomly assigned to the CBGT-C
condition and 6 to an untreated condition. After 2
treatment groups were completed, a third set of 11
subjects were included in the untreated condition“
Simon 1998[2] Low “Patients were randomly assigned using computer
generated random numbers.”
79
[1] James AC et al: Cochrane Database Syst Rev. 2015 Feb 18;2:CD004690
[2] Nieuwenhuijsen K et al: Cochrane Database Syst Rev. 2014 Dec 3;12:CD006237.
74. 割り付けの隠蔽化の評価基準例
80
‘High risk’ of bias
封印されていない封筒の利⽤ (assignment envelopes were used without
appropriate safeguards)
公開された割り付け予定乱数の利⽤ (using an open random allocation
schedule)
‘Low risk’ of bias
中央登録⽅式の利⽤ (using a method of central allocation)
不透明の封印された連続番号の封筒の利⽤ (using a method of
sequentially numbered, opaque, sealed envelopes)
‘Unclear risk’ of bias
無作為に割り付け
(patients were randomly allocated)
Chapter 8: Assessing risk of bias in included studies (http://www.cochrane.org/handbook)
75. 割り付けの隠蔽化の評価事例
研究 評価 判断根拠の記述
Donnan
1990[1]
High “Each patient received an envelope at the end of the
consultation with their general practitioner, which at
random contained either the self-help materials and a
questionnaire or the questionnaire alone. The envelopes
were similar but those containing the self-help material
were heavier.”
Hollinghurst
2010[2]
Low “Randomization was by means of a computer-generated
code, implemented by an individual who was not involved
in the recruitment process, and communicated to the
participant within 48 h of the baseline interview.” “The
allocation was concealed in advance from participants,
researchers involved in recruitment, and therapists.”
81
[1] Mayo-Wilson E et al: Cochrane Database Syst Rev. 2013 Sep 9;9:CD005330.
[2] Nieuwenhuijsen K et al: Cochrane Database Syst Rev. 2014 Dec 3;12:CD006237.
76. 治療者と患者の盲検化の評価基準例
82
‘High risk’ of bias
治療者と患者の盲検化を試みたが,失敗している可能性がある (blinding
of key study participants and personnel attempted, but likely that the
blinding could have been broken)
‘Low risk’ of bias
治療者と患者の盲検化は確実である (blinding of participants and key
study personnel ensured)
‘Unclear risk’ of bias
判断するための⼗分な記載がない
Chapter 8: Assessing risk of bias in included studies (http://www.cochrane.org/handbook)
77. 治療者と患者の盲検化の評価事例
研究 評価 判断根拠の記述
Hees 2013 High “Due to the nature of the intervention, neither patients
nor therapists could be blinded to the patient’s allocation
status.” Both treatments cannot be considered equally
desirable for patients, so risk of performance bias high
Burnand 2002 Low No blinding but risk of performance bias low as both
treatments can be considered equally desirable for
patients “Both treatments involved the same
clomipramine protocol and intensive nursing in a
specialized milieu. In addition, the amount of structured
psychodynamic psychotherapy provided during combined
treatment was comparable to the amount of supportive
care provided during treatment with clomipramine alone.”
83Nieuwenhuijsen K et al: Cochrane Database Syst Rev. 2014 Dec 3;12:CD006237.
78. 評価者の盲検化の評価基準例
84
‘High risk’ of bias
評価者の盲検化を⾏っておらず,盲検化の有無が測定結果に影響する可能
性がある (no blinding of outcome assessment, and the outcome
measurement is likely to be influenced by lack of blinding)
‘Low risk’ of bias
評価者の盲検化を確かに⾏っている (blinding of outcome assessment
ensured, and unlikely that the blinding could have been broken)
‘Unclear risk’ of bias
判断するための⼗分な記載がない
Chapter 8: Assessing risk of bias in included studies (http://www.cochrane.org/handbook)
79. 評価者の盲検化の評価事例
研究 評価 判断根拠の記述
Burnand 2002 High “The individuals who rated the presence and severity of
major depression and HSRS scores at ten weeks were not
blinded to treatment assignment.”
Hollinghurst
2010
High The BDI is a self-report inventory. As participants were
aware of their intervention status, risk of bias high
Hees 2013 Low “Study assessment were conducted by a psychiatrist and a
researcher who where blind to group allocation.” As the
HRSD is a clinician-rated instrument, there is a low risk of
bias for the HRSD outcome
85Nieuwenhuijsen K et al: Cochrane Database Syst Rev. 2014 Dec 3;12:CD006237.
80. アウトカム測定の完全性の評価基準例
86
‘High risk’ of bias
⽋測の理由が,真のアウトカムの値と関連する (reason for missing
outcome data likely to be related to true outcome)
不適切な単⼀代⼊法を利⽤する (potentially inappropriate application of
simple imputation)
‘Low risk’ of bias
アウトカム測定に⽋測がない (no missing outcome data)
‘Unclear risk’ of bias
判断するための⼗分な記載がない
Chapter 8: Assessing risk of bias in included studies (http://www.cochrane.org/handbook)
82. 事前設定したアウトカム報告の評価基準例
88
‘High risk’ of bias
⼀つ以上の主要評価項⽬が事前に設定されていない (one or more
reported primary outcomes were not pre-specified)
‘Low risk’ of bias
研究計画書が⼊⼿可能であり,すべての評価項⽬は事前設定と⼀致してい
る (the study protocol is available and all of the pre-specified (primary and
secondary) have been reported in the pre-specified way)
‘Unclear risk’ of bias
判断するための⼗分な記載がない
Chapter 8: Assessing risk of bias in included studies (http://www.cochrane.org/handbook)
83. 事前設定したアウトカム報告の評価事例
研究 評価 判断根拠の記述
Noordik 2013 High Not all (secondary) outcomes measures announced in the
design paper were reported in the effect study, of which
the data on the HADS-depression subscale
Hees 2013 Low The study protocol is available and all of the study’s pre-
specified (primary and secondary) outcomes that are of
interest in the review have been reported in the pre-
specified way
89Nieuwenhuijsen K et al: Cochrane Database Syst Rev. 2014 Dec 3;12:CD006237.
90. 失敗した臨床試験,結論を粉飾,40~59%
97
[1] Boutron I et al: JAMA. 2010 May 26;303(20):2058-64
[2] Yavchitz A et al: PLoS Med. 2012;9(9):e1001308
[3] Lockyer S et al: Trials. 2013 Nov 6;14:371
[4] Patel SV et al: Dis Colon Rectum. 2013 Dec;56(12):1388-94
92. 粉飾事例,リサーチクエスチョン
99
P : 地域住⺠ (地⽅部/都市部)
I : 複合的⾃殺予防プログラム
C : 通常の⾃殺予防対策
O : ⾃殺死亡者数と⾃傷搬送者数の合計
T : 治療開始3.5年
Ono Y et al: PLoS One. 2013 Oct 9;8(10):e74902
95. 要旨の結論部を粉飾
主要評価項⽬の粉飾
複合的⾃殺予防プログラムは,都市部ではな
く地⽅部で実施できる。
Our findings suggest that this community-based multimodal intervention
for suicide prevention could be implemented in rural areas, but not in
highly populated areas.
副次評価項⽬ + サブグループの焦点化
地⽅部における介⼊の効果は,男性と⾼齢者
で⽰された。
The effectiveness of the intervention was shown for males and for the
elderly in rural areas.
102
[1] Ono Y et al: PLoS One. 2013 Oct 9;8(10):e74902
[2] 奥村: Monthly IHEP 301: 23-28, 2014
118. エビデンスの質の評価基準
128
研究法 エビンデンスの質
R C T → High
Moderate
R C T 以 外 → Low
Very low
降格基準
バイアスへのリスク
研究結果の不⼀致
外挿
広い信頼区間
出版バイアス
Guyatt G et al: J Clin Epidemiol. 2011 Apr;64(4):383-94.
昇格基準
⼤きな効果
⽤量反応性
交絡因⼦の調整
119. Take Home Messages
RCTの読解,臨床家に必須
研究疑問はPICO-Tに定式化
量的変数の評価,平均値差/標準化平均値差
質的変数の評価,リスク⽐/リスク差/オッズ⽐
RCTの質の評価,コクラン,バイアスへのリスク
粉飾に注意
PubMedで⽂献検索,⽂献⼊⼿は施設/個⼈
129