Stopping the active intervention: CARET

Our plain-English summary of Stopping the active intervention: CARET, by D.J. Bowen, M. Thornquist, K. Anderson, et al (Controlled Clinical Trials, 2003).

The study

• Authors: D.J. Bowen, M. Thornquist, K. Anderson, M. Barnett, C. Powell, G. Goodman, G. Omenn, Carotene and Retinol Efficacy Trial
• Journal: Controlled Clinical Trials
• Published: 2003;24(1):39-50
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The Carotene and Retinol Efficacy Trial (CARET) was a large, multicenter randomized chemoprevention trial designed to test a combined lung cancer prevention agent in heavy smokers and workers exposed to asbestos. In January 1996, the CARET Steering Committee decided to stop the intervention due to an adverse effect. This paper describes the decision process used to apply the stopping rules and the activities engaged in by CARET participants and staff to implement the decision. The most important activity was to draft and mail a letter to the participants informing them of the disappointing CARET results and asking them to stop taking the study vitamins and to return any unused study vitamins. The steering committee, with the support of the National Cancer Institute, planned to follow participants for disease endpoints and smoking behavior for 5 years. These activities led to smooth closure of active intervention and maintained high retention rates during the transition.

In plain English

This article described how the Carotene and Retinol Efficacy Trial (CARET) stopped its active intervention early. CARET, a randomized trial in six U.S. cities, tested a daily combination of beta-carotene and retinyl palmitate against placebo for preventing lung cancer in heavy smokers and in men with a recent smoking history and substantial occupational exposure to asbestos. The main outcome results were published elsewhere. At a September 1995 interim analysis, the overall, unweighted relative risk was 1.24 for lung cancer, counting confirmed cases plus those pending review (p-value 0.053), and 1.18 for death from any cause (p-value 0.014). After the trial's monitoring committee deadlocked, a National Cancer Institute ad hoc committee recommended stopping, and the steering committee voted unanimously to end the intervention about 21 months early. The article described letters, press conferences, staff support and transition visits. Within 6 weeks of the announcement, 82% of the 22,607 bottles dispensed had been returned. As of the later transition visits, only 2% of participants refused further follow-up. The authors concluded that a well-coordinated study could respond to a crisis in a very short time.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Descriptive report of the decision process and procedures used to stop the active intervention of a multicenter randomized chemoprevention trial (CARET). It is not a report of the trial's main outcome analysis.
• Who was studied: CARET participants in six U.S. cities. One group was women and men aged 50–69 who were current smokers or had recently quit, with at least 20 pack-years of smoking. The other was men aged 45–69 with a recent cigarette smoking history and substantial occupational asbestos exposure. There were over 17,000 living participants when the intervention stopped in January 1996.
• Exposure: Randomization to beta-carotene and retinyl palmitate combined in a single daily dose, or to placebo. Asbestos exposure was an entry criterion for one participant group. Doses are not given in this article.
• Main results:
  • At the September 1995 interim analysis, the overall, unweighted estimated relative risk of lung cancer (confirmed cases plus those pending review) was 1.24, with a p-value of 0.053. The primary weighted analysis of confirmed lung cancers only also gave a p-value of 0.053.
  • At the same interim analysis, the overall, unweighted estimated relative risk for all-cause mortality was 1.18, with a p-value of 0.014.
  • The safety and endpoints monitoring committee deadlocked over whether to continue. An NCI ad hoc committee then recommended stopping.
  • On January 11, 1996, the steering committee voted unanimously to end the intervention about 21 months early.
  • Results reported to the NEJM, with follow-up through December 15, 1995, gave an unweighted relative risk of 1.28 (95% CI 1.04–1.57) for lung cancer.
  • Results reported to the NEJM gave an unweighted relative risk of 1.17 (95% CI 1.03–1.33) for all-cause mortality.
  • As of 6 weeks after the announcement, 82% of the 22,607 bottles dispensed had been returned. Active and placebo participants returned their bottles at the same rate.
  • Study centers received only 50–60 calls in the first week, and only a few callers were angry.
  • Only 2% of participants refused further follow-up as of the transition visit. All transition visits were completed by February 1997.
• The authors' conclusion: The authors concluded that a well-coordinated study with existing documentation, communication channels and lines of decision making can respond to a crisis in a very short time.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer.

Related studies

• Mailing strategies and costs of recruiting heavy smokers in CARET, a large chemoprevention trial — B. Valanis, J. Blank, et al. (1998)
• Research cost analyses to aid in decision making in the conduct of a large prevention trial, CARET. Carotene and Retinol Efficacy Trial — M.D. Thornquist, N. Urban, et al. (1993)
• Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial — G.S. Omenn, G.E. Goodman, et al. (1996)
• Beta carotene fails to prevent cancer in two major studies; CARET intervention stopped — K. Smigel (1996)
• CARET, the beta-carotene and retinol efficacy trial to prevent lung cancer in asbestos-exposed workers and in smokers — G.S. Omenn, G. Goodman, et al. (1991)
• Recruitment for the beta-carotene and retinol efficacy trial (CARET) to prevent lung cancer in smokers and asbestos-exposed workers — G.S. Omenn, G. Goodman, et al. (1992)

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