Meta analysis and systematic review

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# Meta analysis and systematic review
## ピロリ菌セミナー
### 王　超辰 | Chaochen Wang
### 2019-02-18 pm

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# 目標 objectives

- 系統的レビューの概念を理解する Understand basic ideas of systematic review.

- 臨床疑問を定式化するアプローチを習得する Learn how to formulate an appropriate review question.

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# 系統的レビューとは？ What is a systematic review?

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## 系統的 [Systematic](https://eow.alc.co.jp/search?q=systematic)

〔方法や実行が〕体系立てられた、組織的な、手順どおりの

- The manager told his staff to work in a more systematic way. : 支配人はスタッフにもっと系統立った方法で働くように言った。

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## レビュー [Review](https://eow.alc.co.jp/search?q=review)

〔本，作品・公演などを〕批評［論評］する，批判的に吟味する．

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.center[![tired](pic/tired.gif)]

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# Why do we need systematic review?

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# >1000 new articles/day

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# Most research publshed in medical journal is

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# too poorly done (全然だめ)

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# or

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# insufficiently relevant (不十分)

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# 専門家の意見って何か問題があるの？ What's the problem with "expert opinion"?

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## Nobel prize winning biochemist [**Linus Pauling**](https://ja.wikipedia.org/wiki/%E3%83%A9%E3%82%A4%E3%83%8A%E3%82%B9%E3%83%BB%E3%83%9D%E3%83%BC%E3%83%AA%E3%83%B3%E3%82%B0) used selective quotes from the medical literature to [**"prove"**](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC431183/?tool=pmcentrez) his theory that

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# Vitamin C helps you live longer and feel better

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### 後に，[**系統的レビュー**](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2540847/pdf/bmj00457-0043.pdf)が報告され， 数多くの臨床試験のレポートの中に， ビタミンCが風邪を予防できると書いてある 論文はわずか**2件**

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### 残りの59件の文献によると，**ビタミンCの風邪予防効果はほぼプラセボと変わらない．**

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### 専門家は残念ながら

- 矛盾している意見が多い **conflicting** recommendations

- アドバイスは時代より遅れている their advice frequently **lags behind**

- 最も優れたエビデンスと一致しない場合が多いだろう **inconsistent** with the best available evidence.

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## 系統的レビューで行うこと

ある臨床疑問に対して，**今まで**わかる**すべての証拠**を

- 見つける locate

- 評価する evaluate

- 統合する synthesize

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## 系統的レビューの特徴

- 文献を探す戦略/手順は**系統的，包括的** **systematic and comprehensive** (in its identification of literature)

- 答えたい臨床疑問，使う文献資料，及び評価する・統合する手法は**明確でかつはっきりしたもの** explicit in objectives, materials, and methods.

- **再現**できる **reproducible**

- バイアスを**最小限**にする **minimize bias**

- **信頼できる**結論・エビデンスを提供する provide **reliable** evidence/conclusions

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## どんな人でも，ステップをフォローすれば同じところまで行ける

### Follow the steps, everyone can have the same results.

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![dog stairs](./pic/dog-stairs.gif)

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# The Cochrane Collaboration

### [www.cochrane.org](https://www.cochrane.org/)

![cochrane](./pic/cochrane.png)

???
International non-profit organisation that prepares, maintains, and disseminates systematic up-to-date reviews of health care interventions.

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## [Archibald Cochrane (1909–1988): the father of evidence-based medicine](https://academic.oup.com/icvts/article/18/1/121/674823)

.center[![Archie Cochrane](./pic/ArchieCochrane.png)]

> “It is surely a great criticism of our profession that we have not organised a **critical summary, by speciality and subspeciality**, adapted **periodically**, of all randomised controlled trials”.

> -- (Cochrane 1979)

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# 臨床疑問の定式化 Ask an answerable question

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## To assess the effects of 
## [**XX Intervention or comparison**]
## for 
## [**XX health problem**] 
## in 
## [**XX types of people**]

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### 比較試験 -- **PICO** controlled trials

1. The **P**opulation/**P**articipant Who are the relevant patients?

22. The **I**ntervention What is the exposure that you are interested in (drug, food, surgery, chemical)?

3. The **C**omparator or **C**ontrol What is the control or althernative exposure that you want to compare with the one you are interested in?

4. The **O**utcome What are the patient-relevant consequences of the exposure?

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## 急性心筋梗塞の患者において，アスピリンは生存率を上げるか？ Does aspirin improve survival after acute mycardial infarction?

???
この質問は答える質問だと思いますか？

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### (P)急性心筋梗塞の患者に， (I)毎日一回アスピリンを投与することは (C)毎日一回プラセボを投与すると比べ， (O)5年間の生存率は高くなるか？

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### 公衆衛生的な質問 -- **SPICE** questions about public health interventions

1. **S**etting: What is the context of the question? (e.g. European countries, low-middle income countries, Japan, etc.)

2. **P**erspective: Who are the (potential) users of the outcomes? (e.g. pregnant women, new-born babies, middle school students, etc.)

2. **I**ntervention: What is the intervention to them? (e.g. maternal handbook，screen and treatment of _H. pylori_, etc.)

2. **C**omparison What are the alternatives? (e.g. control groups without maternal handbook, or screen and treatment of _H. pylori_, etc.)

3. **E**valuation How to measure if the intervention is successful? (e.g. mortality rate of infants, vaccine rate of babies, gastric cancer in 10-20 years)

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## 若者での喫煙をどうすれば防げる？ What is the best strategy to prevent smoking in young people/adolescents?

???
この質問は答える質問だと思いますか？

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## Are mass media (or school-based or community-based) interventions effective in preventing smoking/lowering the prevalence of smokers in young people/adolescents in Japan?

???
Setting: in Japan

Perspective: young people

Intervention: mass media (or school-based or community-based) interventions

Comparison: without the interventions

Evaluation: smokers proportion

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### 関連する研究をすべて含む

- 疑問に解答可能なエビデンスをすべて網羅する検索法：

- 電子検索(PubMed, EMbase, Cochrane library)
	- 引用文献の検索(孫引き)
	- ハンドサーチ
	- 著者への問い合わせ

- 検索方法を明記すること

- 除外基準
	
	- 2人以上が独立に検索し，同じ論文・研究を特定できるまで示す 
	
- 出版バイアスの分析

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### 選んだ論文の批判的吟味する

- 検索で選んだ論文の質をチェックすべき
	- RCT(randomized controlled trial)のチェックポイントを使う
	
.center[![check](./pic/evaluation.png)]

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### 研究結果の一貫性があるか

- Forest plotを使うことが多い
	- 推定値が同じ方向にあるか
	- 95%信頼区間が重なるか
	
.center[![forest](./pic/forest.png)]

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### 出版バイアス

- 研究の規模（被験者数）と有効性（効果の大きさ）を使う
	- 規模の小さい研究では，偶然大きな有効性が出やすい
	
.center[![bias](./pic/bias.png)]

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### 臨床シナリオ

- あなたの父親が働く会社の健康保健組合では，40歳以上の家族なら無料で健康診断を受けられる．しかし，母親は健康診断は意味ないとしてずっと受けずにきた．

- しかし，最近芸能人やスポーツ選手でも立て続けに癌になったり，死亡したケースもあったので，心配になった母親は医学部で学ぶあなたに，健康診断を受けたほうがいいのかを尋ねた．

- あなたは，今日の実習を受けて，健康診断の有効性について系統的レビューの論文を探すことにした．

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### 臨床疑問を定式化

- これは健康診断の有効性についての疑問である．

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	- (P)健常成人が，

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	- (I)健康診断を受けると，

- (C)健康診断を受けない場合に比べて，

- (O)どれぐらい死亡率・罹患率が減るか？

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### エビデンスの検索

- 健康診断のキーワード: health check, medical examination, medical checkup

- 死亡・罹患率のキーワード：mortality, morbidity

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# AUTHORS' CONCLUSIONS:

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## Systematic offers of health checks are unlikely to be beneficial and may lead to unnecessary tests and treatments.

[**pdf for downloading the paper**](https://github.com/winterwang/seminar_2019_meta/raw/gh-pages/Krogsb-ll_et_al-2019-Cochrane_Database_of_Systematic_Reviews.pdf)

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# Questions?

![questions](./pic/questions.gif)