Académique Documents
Professionnel Documents
Culture Documents
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)
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
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
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.
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 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 +
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