Clinical research standards

Food and Drug Administration. 1975. New drugs for investigational use adoption of informational clinical research standards acceptance of foreign data . Federal Register 40(69) 16052-16057. 

Statisticians in the Pharmaceutical Industry (PSI), at http //www.psiweb.org. They have published the excellent Guidelines for Standard Operating Procedures for Good Statistical Practice in Clinical Research, at http //psiweb.org/pdf/gsop.pdf. 

The motility of the small bowel has been studied in great detail in experimental, physiological and clinical research [21, 71, 106, 107,109], and the patterns are well defined in man [21, 23, 110], Although a standard test of intestinal motor activity with regard to the efficiency of mechanical luminal clearance is not yet established for clinical use, means to evaluate this function have been proposed. 

Recall that liability for malpractice requires proof that the defendant-physician violated not the jury s standards, but the standards of fellow practitioners when prescribing DES. The allocation of the liability risks in the DES cases between manufacturer and physician is only illustrative rather than prescriptive of the form of allocation that will occur for the products of pharmacogenomics. The main thrust of the DES cases is to illustrate that the standard of care for physicians undergoes a major shift when physicians are operating on the frontiers of medical practice or engaged in clinical research. This allows for the manufacturer s responsibility to be derivative of the physician s duty to deal "fairly" with patients with regard to the risks. 

Sponsor companies use quality assurance units independent of the clinical research group to audit medical operations. Their role is to ensure that regulatory standards and company policies and procedures for clinical research are being followed in all countries where research is being conducted. 

There are of course practical considerations in clinical research. We may find patient recruitment difficult in single centre studies and this is one of the major drivers to multicentre and multinational trials. Alternatively, we may need to relax the inclusion/exclusion criteria or lengthen the recruitment period. Unfortunately, while each of these may indeed increase the supply of patients they may also lead to increased variability that in turn will require more patients. A second issue is the size of the CRD which, if it is too small, will require a large number of patients. In such circumstances we may need to consider the use of surrogate endpoints (Section S.3.3.2). Finally, the standard deviation may be large and this can have a considerable impact on the sample size - for example, a doubling of the standard deviation leads to a four times increase in the... 

The mission of clinical research is to provide scientifically appropriate and accurate information about new treatments in patients, keeping the safety of the patient as absolute priority referring to the law of Hippocrates Nil nocere (Not to harm). An additional ethical aspect of clinical research is the demand of high scientific standards. Therefore ... at the start of the trial, there must be a state of clinical equipoise regarding the merits of the regimens to be tested, and the trial must be designed in such a way as to make it reasonable to expect that, if it is successfully conducted, clinical equipoise will be disturbed (Freedman, 1987). 

While it s true that clinical trials offer no guarantees, when standard treatments fail, or none exist, clinical research trials sometimes can offer hope. People can reduce the confusion and uncertainty that often comes with deciding whether or not to participate in a clinical trial by obtaining all the information available on various Web sites, through phone calls, within FDA, HHS, and NIH offices, and from patient advocacy organizations. 

In Part V, we examine research and ethics. Increasingly, clinical research is undertaken in multi-center studies involving numerous countries and jurisdictions. Argentinian bioethicist Florencia Luna, a past president of the International Association of Bioethics, introduces one of the major issues debated in recent years in international research ethics in this context, namely the question of what constitutes appropriate standards of care for participating patients. The line taken by the U.S. National Institutes of Health and many American bioethicists has been that it is acceptable for developed world sponsors of such trials to provide less than the best proven therapeutic means of treatment to the trial participants. Developed world-based bioethicists do not always agree and Luna explains why. 

The requirements outlined in the CFR are legally enforceable by the U.S. FDA. In addition to the above-mentioned documents, the FDA has guidance documents that are not legal requirements but do provide direction on acceptable standards for clinical research. They are as follows ... 

All IRBs are ultimately responsible for the unbiased determination of whether a proposal for clinical research is acceptable in terms of the standards of professional practice, the institution or individual undertaking the research, and the patient population. Therefore, proposals considered for approval at convened meetings must receive approval by the majority of the members present at that meeting. 

Centralizing clinical research operations Standardizing contracts and operating procedures Training and accrediting staff... 

Over time, the teams expanded to as many as 50 people, with members from basic and clinical research, toxicology, marketing, regulatory affairs, and quality standards and maybe some lawyers. The entire team for one major drug. 

Official standards are absolutely necessary to ensure the quality, reliability, and homogeneity of herbal products for consumers. Standardized products are paramount to those in healthcare planning to conduct clinical research with these products. Independent laboratories and university-affiliated research reports have documented the considerable variation that exists in terms of quality and reliability in these products. Abroad, the ESCOP, composed of manufacturers of herbal medicines and herbal associations, is working with European research groups to develop quality-control standards for the production of natural products. This committee is developing monographs for incorporation into such references as the British Herbal Pharmacopoeia and the British Herbal Compendium. 

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