SELECT CONTINUES!ACKNOWLEDGEMENTS

SUPPORT: SELECT is supported in part by grants 5-U10-CA-37429 and P30-CA015704 from the National Cancer Institute, Division of Cancer Prevention, National Institutes of Health, Department of Health and Human Services; the Office of Research on Minority Health, Department of Health and Human Services; and supported in part by the National Center for Complementary and Alternative Medicine.

TRIAL REGISTRATION: clinicaltrials.govidentifier: NCT00006392

Notifying Study Participants of Increased Prostate Cancer Risk Due to Vitamin EAnderson K1, Hartline J1, Marrah D1, Harris-Talley J1, Goodman P1, Klein E2

1SWOG Statistical Center, 2Cleveland Clinic Lerner College of Medicine

SELECT, the SELenium andvitamin E Cancer prevention Trial, funded by the National Cancer Inst itute and conducted by SWOG, was designed to see if one or both of these dietary supplements could prevent prostate cancer. SELECT opened in 2001 in over 400 study sites in the U.S., including Puerto Rico, and Canada and ended recruitment in 2004 with 35,533 participants. In 2008, we reported that neither studysupplement prevented prostate cancer. The results also showed a non-statistically significant increase in prostate cancer risk for those men taking vitamin E alone. Participants were told what Study Supplements they were taking and to stop taking their Study Supplements. Starting in 2009 the study transitioned to annual follow-up by mail, known as Centralized Follow-Up (CFU). When the new study results were released in October 2011, 17,583 of the original 35,533 participants were on CFU.

May 2011The Data and Safety Monitoring Committee reviewed analyses showing that participants who took the study supplements of vitamin E (400 IU per day) and a placebo for selenium had a statistically significant (p=.008) 17% higher risk of prostate cancer than those who took two placebos. They recommended these results be made public.

May – September 2011Study investigators and statisticians prepared a manuscript. Study leadership including the National Cancer Institute, SWOG and SELECT Coordinating Center staff prepared Questions and Answers (http://www.cancer.gov/newscenter/qa/2008/selectqa) and a national press release, and drafted a letter for study participants. The participant letter was reviewed and edited by the SELECT Participant Advisory Board.

October 7, 2011Letters, including a reminder of what Study Supplements they had taken, were mailed to 17,583 participants on CFU.

October 12, 2011 - Vitamin E and the Risk of Prostate Cancer: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was published in JAMA 2011; 306(14) 1549-1556. With the publication of the article, JAMA also issued a video release on the findings featuring Eric Klein, M.D., lead author, which over the next few days was shown via a multitude of news outlets to a “Total Verified Nielsen Audience” just shy of 250 million viewers.

Excerpt from article: “The unadjusted absolute increase in risk compared with placebo for vitamin E was 1.6 prostate cases per 1,000 person years. That means that over the course of one year, for every 10,000 older men who take vitamin E supplements in the dose and formulation used in SELECT, 16 additional prostate cancer cases could be expected to be diagnosed.”

Given that reliable estimates of supplement use suggest the number of older men taking 400IU or more of vitamin E is well into the millions, the SELECT results imply that thousands of prostate cancer cases a year in the United States could be prevented if vitamin E supplementation in this formulation and dose were discontinued among older men.

October 5, 2011A confidential email was sent to 391 Study Site Investigators and Head CRAs to notify them of the pending release of the information to the public. For those participants whodid not transition to CFU a letter was provided at a secure website. Site staff had the option to distribute this letter to their former SELECT participants.

October 11, 2011A national press release was prepared by NCI and the SELECT public website was updated with the recent study results.

T i m e l i n e o f E v e n t s S o c i a l M e d i aMonitoring Period: October 11 – October 14, 2011

During this time, there were 5,980 social media postings (not including mainstream news) on the topic of prostate cancer and Vitamin E. A majority of posts on this topic were via Twitter (77.6%)(Figure below).•The posts primarily recounted highlights from the

study and were quite neutral.•The negative post criticized the study for jumping

to the conclusion that their results indicate Vitamin E can cause prostate cancer; this (as well as other alleged errors in the study’s design) was a common theme in the negative comments.•On the neutral posts, there were also several

comments accusing the study of “fear mongering” on behalf of “Big Pharma.”

* This letter was also available in general Spanish.

Scientific Context: Our updated results were released just after two other related news reports. One report was the release of the recommendations by the US Preventive Services Task Force which stated that Prostate-Specific Antigen (PSA) screening results in small or no reductions in prostate cancer-specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary. The other report was the results of the Iowa Women’s Health Study which assessed the use of vitamin and mineral supplements in relation to total mortality in over 38,722 older women based on self-report. They concluded that several commonly used dietary vitamin and mineral supplements may be associated with increased total mortality risk.

As of January 31, 2012:

•Coordinating Center staff have responded to over 300 emails, letters, and phone calls regarding the study results.

•43 of 430 study sites have notified the Coordinating Center that they were sending a letter to their participants who did not transition to CFU.

•No participants on CFU have reported withdrawing due to the recent study results.

•37 former participants joined CFU as a result of hearing about these results. Most of these participants said they didn’t realize SELECT was continuing and others stated they wanted to get any further results directly from the Coordinating Center.

•Most of the participants who contacted the SELECT Coordinating Center wanted to confirm what Study Supplements they were taking or to ask questions about multivitamin use.

C o m m e n t s f r o m P a r t i c i p a n t s :

Will you pay for the treatment of my prostate cancer?

Could the Study Supplements have caused my other health problems?

They should have been looking at natural vitamin E.

I wouldn’t have followed through with my prostate exams and had my prostate cancer caught early if I wasn’t doing this study.

I have been doing this study for years, so why stop now!

If continuing to provide my health information will help someone in the future, then I want to do all I can.