Anda di halaman 1dari 6

LEGEND: Evidence Appraisal of a Single Study

Intervention
Randomized Controlled Trial (RCT) or Controlled Clinical Trial (CCT)
Project/Topic of your Clinical Question: Long-term effects of vitamin E and selenium on risk of prostate cancer in relatively healthy men.

Reviewer: Claudia Konstand Today’s Date: March 7, 2018 Final Evidence Level: 2a
Article Title: Vitamin E and the Risk of Prostate Cancer: The Selenium and Vitamin E Cancer Prevention Trial (SELECT)

Year: First Author: Journal: Journal of the American Medical


2011 Eric A. Klein, MD Association (JAMA)

Do the study aim/purpose/objectives and inclusion/exclusion criteria assist in answering your clinical question?
x Yes No Unknown
• Study Aim/Purpose/Objectives: To determine the long-term effect of vitamin E and selenium on risk of prostate
cancer in relatively healthy men.
• Inclusion Criteria: Healthy men at average risk of prostate cancer based on baseline prostate-specific antigen (PSA) of ≤ 4ng/mL and
normal digital rectal examination (DRE) commencing at age 50 years for black men or at age 55 years for all others.
• Exclusion Criteria: Men under age 50 years (if African American) or 55 years (all others); those with history of prostate cancer; no current use of anticoagulant therapy
other than ≤ 175 mg/day of acetasalicylic acid or ≤ 81 mg/day of acetasalicylic acid with clopidogrel bisulfate; no history of hemorrhagic stroke, and
normal blood pressure were also required because of anti-platelet effects of vitamin E and related findings of the ATBC Study (info gathered from
2009 SELECT paper)

Is a RCT or CCT congruent with the author’s study aim/purpose/objectives above? x Yes No Unknown

Comments: The participants were randomly assigned to four groups: selenium with matching placebo, vitamin E
with matching placebo, both agents, or placebo. The participants were tracked over time to
monitor the incidence of prostate cancer.

When reading the bolded questions, consider the bulleted questions to help answer the main question.
If you are uncertain of your skills in evidence evaluation, please consult a local evidence expert for assistance:
CCHMC Evidence Experts: http://groups/ce/NewEBC/EBDMHelp.htm
Unfamiliar terms can be found in the LEGEND Glossary: http://groups/ce/NewEBC/EBCFiles/GLOSSARY-EBDM.pdf

VALIDITY: ARE THE RESULTS OF THE RCT OR CCT VALID OR CREDIBLE?


1. Were patients randomly assigned to treatment and control groups? x Yes No Unknown
Note: If the study was not randomized, it should be assigned a level for a CCT.

Comments: The participants were randomly assigned to four groups: selenium with matching placebo, vitamin E with matching placebo, both agents, or
placebo. Participants were randomized in a randomized block scheme, where the block was the study site. This insured a balance of the four
treatment groups within each study site (info gathered from 2009 SELECT paper.)
2. Was that randomization conducted appropriately? x Yes No Unknown
• Was the randomization concealed from those responsible for recruiting
subjects?

32,400 men were randomized to selenium, vitamin E, selenium plus vitamin E, and placebo in a double-blinded fashion. Participants were
recruited and followed in community practices, local hospitals and HMOs, and tertiary cancer centers in the US, Canada, and Puerto Rico.
Comments:
• Were patients, parents, clinicians, and analysts masked to which treatment was
being received? Yes; double-blinding; see above.
3. Were the groups similar at the start of the trial, with respect to known
prognostic factors (i.e., demographic and clinical variables)? x Yes No Unknown

Comments: Based on inclusion/exclusion criteria, all men were similar (all participants at average risk of prostate
cancer, no history of prostate cancer).
Copyright © 2006-2012 Cincinnati Children's Hospital Medical Center; all rights reserved. April 9, 2012
CCHMC Evidence Collaboration: James M. Anderson Center for Health Systems Excellence | Center for Professional Excellence | Edward L. Pratt Research Library
Evidence-Based Decision Making – www.cincinnatichildrens.org/evidence Page 1 of 4
LEGEND: Evidence Appraisal of a Single Study
Intervention
Randomized Controlled Trial (RCT) or Controlled Clinical Trial (CCT)

4. Aside from the experimental treatment, were the groups treated equally? x Yes No Unknown

Comments: Monitored every 6 months with an annual physical examination including blood pressure, weight, and smoking status; participants who
developed prostate cancer during the study were monitored annually thereafter. Participants were recommended to undergo PSA and DRE
testing and prostate biopsy based on the standard of care in their community and in accordance with the participant's preference. To facilitate
adherence, a multivitamin containing no selenium or vitamin E was offered.

Copyright © 2006-2012 Cincinnati Children's Hospital Medical Center; all rights reserved. April 9, 2012
CCHMC Evidence Collaboration: James M. Anderson Center for Health Systems Excellence | Center for Professional Excellence | Edward L. Pratt Research Library
Evidence-Based Decision Making – www.cincinnatichildrens.org/evidence Page 2 of 4
LEGEND: Evidence Appraisal of a Single Study
Intervention
Randomized Controlled Trial (RCT) or Controlled Clinical Trial (CCT)
5. Were all patients who entered the trial accounted for at its conclusion? x Yes No Unknown
• Was there a low rate of attrition? - yes (~10%)
Note: If greater than 20% lost to follow up, bias may be of greater concern.

Comments: All participants accounted for in Figure 1 for both original and updated analyses

6. Were patients accounted for (and analyzed) in the groups to which they were
randomized (i.e., intention-to-treat analysis)? Yes No x Unknown

Comments: Not addressed; authors accounted for a constant 10% drop-in rate, defined as
participants on placebo who are taking active supplementation off-study (described in 2009 SELECT
paper methods)
7. Was the study process long enough to fully study effects of the intervention? x Yes No Unknown

Comments: Study began in 2001 and continued until 2011; mean follow-up for the original 2009 study was 5.5
years; the 2011 study added 54,464 additional person-years of follow-up since the primary report,
an increase of 23%.
8. Were instruments used to measure the outcomes valid and reliable? x Yes No Unknown

Comments: Main outcome measure of prostate cancer incidence determined by routine clinical management and
confirmed by central pathology review

9. Was there freedom from conflict of interest? Yes No x Unknown


• Sponsor/Funding Agency or Investigators
Comments: Funding and potential conflicts of interests: National Cancer Institute, Merck, Wyeth/Pfizer, AstraZeneca,
Abbott, GlaxoSmithKline, Janssen, Amgen, Novartis, Firmagon, Cancer Prevention Pharmaceuticals, Public Health Service
Coorperative Agreement
RELIABILITY: ARE THESE VALID STUDY RESULTS IMPORTANT?
10. Did the study have a sufficiently large sample size? x Yes No Unknown
• Was there a power analysis?
With a sample size of 32,400 men, using a 1-sided alpha-level of .005 (equivalent to a 2-sided alpha level of 0.01), there was 96% power to detect a 25%
reduction in prostate cancer for either of the single agents (versus placebo), 89% power to detect a 25% reduction for the combination (versus an active
single agent) and greater than 99% power to detect a 44% reduction of the combination (versus placebo).
• Did the sample size achieve or exceed that resulting from the power analysis? yes
• Did each subgroup also have sufficient sample size (e.g., at least 6 to 12 participants)? yes
Comments:
11. What were the main results of the RCT or CCT?

This report includes 54 464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the pla-cebo
(referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-
1.36, P=.008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P=.18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22,
P=.46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the
combination. Table 1 lists the baseline participant characteristics; Table 2: Diagnostic Testing results; Table 3: Number and Risk of Prostate Cancers; Figure 2: Cumulative Incidence of Prostate Cancer; Table: Clinical
and Pathological Characteristics of Incident Prostate Cancers; Table 5: Secondary End points

• What was the effect size? (How large was the treatment effect?) Not listed by the authors
What were the measures of statistical uncertainty (e.g., precision)? 95-99% CIs,
(Were the
Copyright © 2006-2012 resultsChildren's
Cincinnati presented with Medical
Hospital Confidence Intervals
Center; orreserved.
all rights Standard Deviations?)
April 9, 2012
CCHMC Evidence Collaboration: James M. Anderson Center for Health Systems Excellence | Center for Professional Excellence | Edward L. Pratt Research Library
Evidence-Based Decision Making – www.cincinnatichildrens.org/evidence Page 3 of 4
LEGEND: Evidence Appraisal of a Single Study
Intervention
Randomized Controlled Trial (RCT) or Controlled Clinical Trial (CCT)
12. Were the results statistically significant? x Yes No Unknown

Comments: Yes; p value for vitamin E group was statistically significant at p=0.008; after adjusting for the marginal effects of
vitamin E and selenium, the interaction between vitamin E and selenium was statistically significant (p=0.02)

Copyright © 2006-2012 Cincinnati Children's Hospital Medical Center; all rights reserved. April 9, 2012
CCHMC Evidence Collaboration: James M. Anderson Center for Health Systems Excellence | Center for Professional Excellence | Edward L. Pratt Research Library
Evidence-Based Decision Making – www.cincinnatichildrens.org/evidence Page 4 of 4
LEGEND: Evidence Appraisal of a Single Study
Intervention
Randomized Controlled Trial (RCT) or Controlled Clinical Trial (CCT)
13. Were the results clinically significant? x Yes No Unknown
• If potential confounders were identified, were they discussed in relationship
to the results?

Comments: The unadjusted absolute increase in risk of cases of prostate cancer per 1000 person-years compared with placebo was 1.6 for vitamin E, 0.8
for selenium, and 0.4 for the combination. Potential confounders were not identified in this paper.

14. Were adverse events assessed? Yes No x Unknown

Comments: No adverse effects of the 4 treatment types were reported; patient flow diagram (Figure 1) describes
deaths and losses to follow-up

APPLICABILITY: CAN I APPLY THESE VALID, IMPORTANT STUDY RESULTS TO TREATING MY PATIENTS?
15. Can the results be applied to my population of interest? Yes No x Unknown
• Is the treatment feasible in my care setting?
• Do the patient outcomes apply to my population or question of interest?
• Are the likely benefits worth the potential harm and costs?
• Were the patients in this study similar to my population of interest?
Comments:

16. Are my patient’s and family’s values and preferences satisfied by the treatment
and its consequences? Yes No x Unknown
Comments:

17. Would you include this study/article in development of a care recommendation? x Yes No Unknown
Comments:

_
ADDITIONAL COMMENTS OR CONCLUSIONS (“TAKE-HOME POINTS”):
Good quality RCT demonstrating that dietary
supplementation with vitamin E significantly increases the
risk of prostate cancer among healthy men

_
_
_

Copyright © 2006-2012 Cincinnati Children's Hospital Medical Center; all rights reserved. April 9, 2012
CCHMC Evidence Collaboration: James M. Anderson Center for Health Systems Excellence | Center for Professional Excellence | Edward L. Pratt Research Library
Evidence-Based Decision Making – www.cincinnatichildrens.org/evidence Page 5 of 4
LEGEND: Evidence Appraisal of a Single Study
Intervention
Randomized Controlled Trial (RCT) or Controlled Clinical Trial (CCT)

QUALITY LEVEL / EVIDENCE LEVEL


• Consider each “No” answer and the degree to which this limitation is a threat to the validity of the results, then check the
appropriate box to assign the level of quality for this study/article.
• Consider an “Unknown” answer to one or more questions as a similar limitation to answering “No,” if the information is not
available in the article
THE EVIDENCE LEVEL IS: x Good Quality RCT [2a]
Lesser Quality RCT [2b]
Good Quality CCT [3a]
Lesser Quality CCT [3b]
Not Valid, Reliable, or Applicable

Table of Evidence Levels


TYPE OF STUDY / STUDY DESIGN

Published Expert Opinion


(Before/After, Time Series)

Mixed Methods Study


Systematic Review

Quality Improvement

Published Abstracts
Qualitative Study

– Prospective
Meta–Analysis

Computer Simulation
– Retrospective

Cross – Sectional

Local Consensus
Case – Control

Economic Analysis
Descriptive Study

Decision Analysis

Case Reports
DOMAIN OF

N-of-1 Study
Longitudinal
Cohort

Epidemiology
CLINICAL

Bench Study
Case Series
Cohort

Guidelines
QUESTION

(PDSA)
RCT +

Intervention
2a
CCT +

Treatment, Therapy, 1a 3a 4a 3a 4a 4a 4a 4a 4a 4a 2/3/4 5a 5a 5a 5a 5a


5
Prevention, Harm, 1b 2b 3b 4b 3b 4b 4b 4b 4b 4b 4b a/b 5b 5b 5b 5b 5b
Quality Improvement
+
RCT = Randomized Controlled Trial; CCT = Controlled Clinical Trial

Development for this appraisal form is based on:


1. Guyatt, G.; Rennie, D.; Evidence-Based Medicine Working Group; and American Medical Association.: Users' guides to the medical literature: a manual for evidence-
based clinical practice. Users' guides to the medical literature: a manual for evidence-based clinical practice: "JAMA & archives journals." Chicago, IL, 2002
2. Melnyk, B. M. and E. Fineout-Overholt (2005). Evidence-based practice in nursing & healthcare: a guide to best practice. Philadelphia, Lippincott Williams & Wilkins.
3. Lohr, K. N. and T. S. Carey (1999). "Assessing "best evidence": issues in grading the quality of studies for systematic reviews." Joint Commission Journal on Quality
Improvement 25(9): 470-9.
4. Fineout-Overholt, E. and L. Johnston (2005). "Teaching EBP: asking searchable, answerable clinical questions." Worldviews Evid Based Nurs 2(3): 157-60.
5. Jerosch-Herold, C. (2005). "An evidence-based approach to choosing outcome measures: a checklist for the critical appraisal of validity, reliability and responsiveness
studies." British Journal of Occupational Therapy 68(8): 347-53.
6. Phillips, et al: Oxford Centre for Evidence-based Medicine Levels of Evidence, 2001. Last accessed Nov 14, 2007 from http://www.cebm.net/index.aspx?o=1025.
7. Fineout-Overholt and Johnston: Teaching EBP: asking searchable, answerable clinical questions. Worldviews Evid Based Nurs, 2(3): 157-60, 2005.

Copyright © 2006-2012 Cincinnati Children's Hospital Medical Center; all rights reserved. April 9, 2012
CCHMC Evidence Collaboration: James M. Anderson Center for Health Systems Excellence | Center for Professional Excellence | Edward L. Pratt Research Library
Evidence-Based Decision Making – www.cincinnatichildrens.org/evidence Page 6 of 4