Hennekens C H, Buring J E
Department of Medicine Harvard Medical School, Boston, Massachusetts 02215-1204.
Cancer. 1994 Nov 1;74(9 Suppl):2625-9. doi: 10.1002/1097-0142(19941101)74:9+<2625::aid-cncr2820741807>3.0.co;2-o.
Observational studies and randomized trials provide relevant and complementary information to a totality of evidence on which to base rational clinical decision making for patients and overall health policy for the general population. Observational studies are particularly useful for detecting moderate to large effects. The 15- to 20-fold greater risk of lung cancer among long term cigarette smokers was established by case-control and prospective cohort studies. The approximate 80% increased risk of coronary heart disease associated with current smoking also has been reliably demonstrated in observational studies. However, as the relative risk gets smaller, there is increasing concern that unmeasured or unknown confounding variables may account for all or part of any observed association. For these reasons, reliable inferences about interventions likely to confer small to moderate benefits will emerge only from randomized trials of sufficient sample size and duration of treatment and follow-up. Dietary variables have been postulated to account for as much as 35% of all human cancers. However, the hypothesized benefit of any specific dietary constituent, such as the antioxidant beta-carotene, is likely to be modest in size, on the order of a 20-30% reduction in risk. Therefore, although a large number of observational studies have demonstrated that individuals with higher dietary intakes or blood levels of beta-carotene have lower risks of cancer, only randomized trials can address this hypothesis definitively. Such trials, however, must be of sufficient duration to allow for the development of an anticancer effect. This may mean a decade or more based on the analogy with smoking cessation and decreased risks of lung cancer. Several ongoing large-scale trials are testing beta-carotene and other promising cancer chemoprevention agents, and their results will provide clear evidence on the balance of benefits and risks of these interventions.
观察性研究和随机试验为形成合理的临床决策以治疗患者以及制定总体人群的整体健康政策提供了相关且互补的证据。观察性研究对于发现中度至重度影响尤为有用。长期吸烟者患肺癌的风险高出15至20倍，这是通过病例对照研究和前瞻性队列研究确定的。当前吸烟与冠心病风险增加约80%的关联也在观察性研究中得到了可靠证实。然而，随着相对风险变小，人们越来越担心未测量或未知的混杂变量可能解释了任何观察到的关联的全部或部分。出于这些原因，只有通过样本量足够大、治疗和随访时间足够长的随机试验，才能得出关于可能带来小到中度益处的干预措施的可靠推断。据推测，饮食变量在所有人类癌症中所占比例高达35%。然而，任何特定饮食成分（如抗氧化剂β-胡萝卜素）的假定益处可能规模不大，风险降低幅度约为20-30%。因此，尽管大量观察性研究表明，饮食中β-胡萝卜素摄入量较高或血液中β-胡萝卜素水平较高的个体患癌症的风险较低，但只有随机试验才能明确验证这一假设。然而，此类试验必须持续足够长的时间以产生抗癌效果。根据戒烟与肺癌风险降低的类比，这可能意味着十年或更长时间。几项正在进行的大规模试验正在测试β-胡萝卜素和其他有前景的癌症化学预防剂，其结果将为这些干预措施的利弊平衡提供明确证据。
