临床试验:规模越大越好?

Chronobiologia Pub Date : 1993-07-01
F Halberg, C Bingham, G Cornélissen
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引用次数: 0

摘要

时间生物学方法不仅仅是在确定药物有用后可能考虑的微调;一开始花费很少,一项0期时间生物学试验可能表明,如果在错误的时间给药,某种药物可能弊大于利。至少同样重要的是,时间生物学方法可以识别仅在适当时间起作用的药物的有效性。当不同的时间生物学时间导致相同药物每周总剂量相反的效果时,很明显时间不能与剂量分开。时间结构调整的给药模式可以使恶性生长的非期望刺激和生存时间的缩短与期望的生长抑制和生存时间的延长之间产生差异。香菇多糖的经验,即这种免疫调节药物可以刺激和抑制癌症的发展,可能适用于在生物反应调节剂的时代更多的治疗药物。特别重要的一点是,免疫刺激剂不应该在它可以成为免疫抑制剂的时候使用。在这种情况下,让许多人感到惊讶的是,时间生物学设计也具有成本效益。大多数学者认为,如果进行六次检查,费用将增加六倍,需要六倍的患者和六倍的工作量。我们相信,我们已经证明了相反的情况是正确的:如果是这样,那么关于时间生物计量学的利弊和忽视它的讨论就变成了一种道德问题。现状如图1-5所示。已给出的例子表明,某些效果只能在一定时间内以所使用的剂量获得。图8显示了通过根据非特异性标记节律定时治疗,预期抗癌效果加倍。认识到时间生物学设计的力量,以及在非侵入性确定的标记时间中发现的大振幅节律,是一个可以利用的挑战,特别是在癌症治疗中。标志物测定仍然很昂贵,但一旦支付了开发成本,建立了市场,并对社区进行了自助培训,现在大多数糖尿病患者为自己承担的责任也可以由癌症患者承担。(摘要删节为400字)
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Clinical trials: the larger the better?

A chronobiologic approach is much more than fine-tuning that may perhaps be considered after a drug has been identified as useful; at very little cost at first, a Phase 0 chronobiologic trial may show that there is danger that a given drug may do more harm than good when administered at the wrong time. At least equally important, the chronobiologic approach may recognize the usefulness of a drug that is active only at the proper time. When different chronobiologic timing results in opposite effects from the same total weekly dose of the same drug, it is clear that timing cannot be separated from dosing. The time structure-adjusted pattern of drug administration can make the difference between the undesired stimulation of a malignant growth and shortening of survival time and the desired growth inhibition and prolongation of survival. The experience with lentinan, namely that this immunomodulating drug can stimulate as well as inhibit the development of a cancer, may apply to many more therapeutic agents in a day and age of biologic response modifiers. It is a point of particular importance that an immunostimulator ought not be given at a time when it can be an immunosuppressor. What is surprising to many under these circumstances is that chronobiologic designs are also cost-effective. Most scholars believe that if a test is carried out at six times, it will cost six times more, will require six times more patients and six times more work. We believe we have shown that the reverse holds true: if so, the discussion of the pros and cons of chronobiometry and of neglect thereof becomes one of ethics. Figures 1-5 depict the status quo. Examples have been given to show that some effects can be obtained only at certain times with the dose used. Figure 8 reveals the doubling of the desired anticancer effect by timing treatment according to an unspecific marker rhythm. The recognition of the power of chronobiologic designs coupled to the discovery of large-amplitude rhythms in non-invasively determined marker chronomes is a challenge that can be exploited, particularly in the treatment of cancer. Marker determinations are still expensive, but once the cost of their development is paid, a market is established, and the community is trained in self-help, the responsibility now assumed by most diabetic patients for themselves can also be shouldered by cancer patients.(ABSTRACT TRUNCATED AT 400 WORDS)

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