Epidemiologie

          Intervenční studie – Mendelian randomisation – systematické přehledy literatury

                                              Cvičení


Příklad 1


Effects of Long-term Vitamin E Supplementation on Cardiovascular Events and Cancer: A Randomized
Controlled Trial

The HOPE and HOPE-TOO Trial Investigators

JAMA. 2005;293(11):1338-1347. doi:10.1001/jama.293.11.1338


Context Experimental and epidemiological data suggest that vitamin E supplementation may prevent
cancer and cardiovascular events. Clinical trials have generally failed to confirm benefits,
possibly due to their relatively short duration.

Objective To evaluate whether long-term supplementation with vitamin E decreases the risk of
cancer, cancer death, and major cardiovascular events.

Design, Setting, and Patients A randomized, double-blind, placebo-controlled international trial
(the initial Heart Outcomes Prevention Evaluation [HOPE] trial conducted between December 21, 1993,
and April 15, 1999) of patients at least 55 years old with vascular disease or diabetes mellitus
was extended (HOPE–The Ongoing Outcomes [HOPE-TOO]) between April 16, 1999, and May 26, 2003. Of
the initial 267 HOPE centers that had enrolled 9541 patients, 174 centers participated in the
HOPE-TOO trial. Of 7030 patients enrolled at these centers, 916 were deceased at the beginning of
the extension, 1382 refused participation, 3994 continued to take the study intervention, and 738
agreed to passive follow-up. Median duration of follow-up was 7.0 years.

Intervention Daily dose of natural source vitamin E (400 IU) or matching placebo.

Main Outcome Measures Primary outcomes included cancer incidence, cancer deaths, and major
cardiovascular events (myocardial infarction, stroke, and cardiovascular death). Secondary outcomes
included heart failure, unstable angina, and revascularizations.



Figure 1





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Otázky:

1.       Popište stručně cíle této studie

2.       Co byla expozice?

3.       Co byla hlavní závislá proměnná?

4.       Jaká byla studovaná populace a kritéria pro vstup participantů do studie?

5.       Jaká byla účast pozvaných?

6.       Co soudíte o velikosti této studie?

7.       Jaké jsou rozdíly v úbytku participantů mezi oběma větvemi studie (Figure 1)?

8.       Table 4: Bez počítání – co soudíte o vlivu suplementace vitamínem 4 na riziko KVO?

9.       Spočítejte relativní rizika pro major vascular events in the primary analysis (Table 4)

10.   Myslíte, že tato relativní rizika jsou statisticky významná?




Příklad 2

Figure 2. Meta-analysis of 7 randomized trials involving 81,788 patients comparing the risk of
cardiovascular death among those randomized to placebo or vitamin E (Breslow-Day test, p = 0.73).
ATBC = Alpha-Tocopherol, Beta-Carotene Cancer Prevention trial; CHAOS = Cambridge Heart Antioxidant
Study; CI = confidence interval; GISSI = Gruppo Italiano per lo Studio della Sopravvivenza
nell'Infarto; HOPE = Heart Outcomes Prevention Evaluation; HPS = Heart Protection Study; PPP =
Primary Prevention Project.


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Figure 3. Meta-analysis of 8 randomized trials involving 138,113 patients comparing the risk of
cardiovascular death among those randomized to placebo or β-carotene (Breslow-Day test, p = 0.12).

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Figure 4. Meta-analysis of 7 antioxidant trials (N = 3,130) studying atherosclerotic disease
progression using imaging techniques. ASAP = Antioxidant Supplementation in Atherosclerosis
Prevention; HATS = HDL Atherosclerosis Treatment Study; SECURE = Study to Evaluate Carotid
Ultrasound Changes in Patients Treated with Ramipril and Vitamin E; SU.VI.MAX = The Supplémentation
en Vitamines et Minéraux Antioxydants; VEAPS = Vitamin E Atherosclerosis Prevention Study; WAVE =
Women's Angiographic Vitamin and Estrogen.


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Otázky:


1.       O jaký typ studií se jedná?

2.       Popište výsledky v grafech 2-4

3.       Jaký je vliv suplementace vitamíny na riziko KVO?

Příklad 3


Otázky:

1.Jaké jsou principy Mendelovské randomizace?

1.Dovedete si představit Mendelovskou randomizaci na vztah antioxidačních vitamínů a rizika KVO?
Jak by taková studie asi vypadala?

3.Jaké informace/data by byly k takové studii potřeba?

4.Podívejte se na obrázek níže (týká se beta-karotenu a diabetu). Dokázali byste tento graf
interpretovat?  (z Perry et al., 2009)


Figure 1