Selection of subjects

In designing and conducting pharmacogenetics studies, researchers must take care in the selection of subject populations. In culling a set of persons which best represents the diversity of an area of the genome, the researcher must consider several questions ... 

Selection of subjects is based on scientific objectives and not on whether the subject is privileged or vulnerable, or because of convenience (Exhibit 6.2). Inclusion and exclusion criteria are well thought out and designed solely to satisfy the scientific basis being put forward. There must be documented evidence to support the choice of selection criteria. 

Epidemiologists need to work diligently to weed out possible bias, in the selection of subjects for study and in the collection of data on exposure to possible causative factors. If, in a given study, an association is found, but bias is identified and cannot be accounted for, it may be that causal inferences can simply never be drawn. 

How about diversity Have we built in a non-discriminatory policy for the selection of subjects Will we include women in the experimental cohort and, for that matter, can we afford to exclude older subjects who are otherwise in good physical health and want to participate After all, they might be the ones most likely to benefit from our drug. 

In selection of subjects, ethical considerations are dominant and limit the deliberate exposure of minors or of others who are unable legally to be volunteer subjects. 

Statistical analysis used and selection of subjects to be included... 

Stage 1 Selection of subjects to be harmonised and nomination of a coordinating pharmacopoeia for each subject... 

Selection of subject matter for the book was, of course, a most difficult task. It is noted that at one time a desk of one of the authors was loaded with three thousand journal papers on the subject ( ). Simply listing the papers relevant to the field in a legible font size would make a book at least half the width of that which you are holding. Ultimately though decisions have to be made regarding... 

Selection of subjects commensurate with the purpose of the study. 

A similar comment holds with regard to selection of subjects. Clinical studies already referred to indicate that those subjects who are more stable and productive beforehand tend to "benefit considerably from the psychedelic experience along the lines of self-actualization, richer creative experience, and enhancement of special abilities and aptitudes" (Savage et al., 1966). Subjects for this pilot study were deliberately selected to be persons with known reputations as creative individuals. In general, we would expect the outcomes of this kind of research to be more fruitful with gifted rather than "merely normal" subjects. 

The method of selection of subjects provides adequate assurance that they have the disease or condition being studied, or evidence of susceptibility and exposure to the condition against which prophylaxis is directed. 

The main theme of the book is the molecular approach to industrial catalysis. The integrated way in which the subject matter has been treated involves many disciplines as a consequence, the writing of the book has been entrusted to a number of authors. The editors envisaged a careful planning and harmonization of the contents of the chapters. The latter is important, because a rigorous selection of subject matter is necessary in order to keep the size of the book within the limits of a practicable textbook. 

During the past thirty years a tremendous volume of literature has dealt with all aspects of solid proplnts. A comprehensive review of all this literature is quite beyond the scope of this Encyclopedia. Indeed an all-inclusive discussion of SP would require an entire Encyclopedia wholly devoted to solid proplnts. The im-practicality of a comprehensive review is not the only reason for limiting the scope of the present article. Solid proplnt literature suffers more than usually from repetition and poor quality. Thus even in a comprehensive review, considerable selectivity of subject matte is imperative. Furthermore, as shown below, certain aspects of SP, in particular cannon propints, have already been treated iri previous Encyclopedia volumes... 

Another uncontrolled trial of a 6-day desensitization procedure in 33 cases has been reported (159). The protocol started with a dose of 0.2 mg rising to 800 mg over 6 days and 32 of the subjects successfully completed the course. In addition, 12 of 14 cases were successfully re-challenged with co-trimoxazole. However, this study lacked a clear description of follow-up or the reasons for the selection of subjects for desensitization or re-chal-lenge, and cannot be used as a basis for recommending this desensitization technique. 

See if selection of subjects is equitable and informed consent is sought and documented in accordance with federal regulations. 

Several mistakes of inference should be avoided by those attempting to assign cause-and-effect relationships. For example, although anecdotes and case reports can suggest testable hypotheses, they should not, by themselves, provide a basis for causal inference, especially in the absence of unbiased selection of subjects, examination of patients for other explanations of the adverse event, and measurement of the frequency of the same adverse event in appropriate control patients. 

As an innovation, this year s Report combines the usual section on Properties and Reactions with the subject of Partial Synthesis into a single chapter. In earlier volumes, selection of subject matter for two separate chapters has perforce been somewhat arbitrary, and has not infrequently resulted in some duplication of material, where authors chose to emphasize different facets of the same piece of work. The present chapter retains the classification of Properties and Reactions used in previous volumes, but groups into additional sections the work which was concerned in particular with aspects of synthesis. 

In the ideal study, the results of aU patients tested with the test under evaluation are contrasted with the results of a single reference standard. If fewer than all patients are verified with the reference standard, then partial verification exists, and verification bias may occur if the selection of subjects for reference testing is not purely random. For example, if selection is associated with the outcome of the index test, or the strength of prior suspicion, or both, then verification bias is certain. In a typical case, some patients with negative test results (test-negatives) are not verified by the reference standard if this involves a costly or invasive procedure, and these patients are not included in the analysis. This may result in an underestimation of the number of false-negative results. 

Selection of subjects - maximizing the signal-to-noise ratio... 

In summary, the selection of subjects to be enrolled in the trial using a list of entrance criteria is an important tool that helps to sharpen the signal-to-noise ratio, thus making the study more powerful. It also helps in understanding the extent to which the study conclusions can be generalized to a broader population of patients than those studied under the clinical trial s artificial conditions. 

The Belmont report describes the basic ethical principles that underlie research involving human subjects respect for persons, beneficence, and justice. The report discusses application of informed consent, assessment of ri.sks and benefits, and selection of subjects. Its regulations require that IRBs have not fewer than five members who have the capability to judge research proposals in terms of community attitudes. Therefore, IRBs must include people whose primary concerns lie in the areas of legal, professional, and community acceptance rather than in the overall scientific design. 

Thus, selection of subjects has the potential to be an ethical dilemma. The Belmont Commission s interpretation of the requirement of justice is seen in the following statement ... 

Statistical analysis used and selection of subjects to be included Timing of any interim analysis Reason for sample size Power of clinical study... 

---