Selection of healthy volunteers for phase I studies

Abstract

Healthy volunteers selection is one of the foundations for phase I results. Safety for volunteers, quality of data and reliability for study results depend on healthy volunteers selection. The selection aim is not to choose normal subjects but to exclude every people with diseases or risk factors which could result in increased danger for themselves or confuse the interpretation of study results. The selection procedure needs to define a list of relevant disease to be excluded depending on phase I objectives (tolerability, pharmacokinetic, pharmacodynamic). The choice of diseases is based on frequency, potential risk for the subjects or for the study. The selection is mainly a clinical process but because of asymptomatic diseases a laboratory screening is necessary and useful. This laboratory screening requires that a basic common list of relevant tests be determined and an appropriate method of cut-off point determination based on an evaluation of the risk of disease. According to the drug or the objective of the study adaptation of the procedure must be carried out. The percentage of erroneous inclusion of subjects is the best validation criterion for selection. The use of such a selection methodology by the author's group in Lyon results in a 50% exclusion for 494 first seen subjects with only 1% erroneous inclusion and 6% exclusion for laboratory test anomalies.

Selecting healthy volunteers in specific populations: a retrospective analysis of clinical and laboratory screening

“…The originality of this study is to include five different sub‐populations of potentially healthy volunteers with different clinical characteristics, despite a subject sample smaller than that of the study by Singh and Williams and Sibille [6,7]. We show here that the abnormalities detected differ between the sub‐populations.…”

“…Volunteers who have been excluded for protocol‐specific medical causes could have been included in a study if the main criteria were respected. In our study, the rate of ineligibility for non‐specific medical causes (31.7%) is between that of Sibille (45%) [7] and that of Singh and Williams (10.9%) [6]. But the study by Sibille does not mention any telephone screening before the volunteer attends the Research Center.…”

“…As the prevalence of allergies is currently increasing in Europe [12,13], we believe that a thorough search for allergic history is a key point in the selection process of healthy volunteers. Similarly, neither Singh and Williams [6] nor Sibille [7] mentioned ineligibility causes resulting from an abnormal eating behaviour. Abnormal eating behaviour is rarely self‐considered as pathological but is increasingly frequent, particularly among young women, and may be associated with kidney, liver or cardiac complications [14–16].…”

Integrated analysis of toxicity data of two pharmaceutical immunosuppressants and two environmental pollutants with immunomodulating properties to improve the understanding of side effects—A toxicopathologist׳s view

“…Likewise, in human populations from different countries variability of laboratory values was observed (MiriDashe et al, 2014;Zeh et al, 2011). In studies in human volunteers, unwanted variations can be reduced by setting of appropriate selection criteria (Sibille, 1990;Sibille et al, 1999). Depending on the disease and parameters studied, interindividual variation in controls can be larger than in patients (Wagener et al, 2013).…”

Incidence and Predictors of Screen Failures Due to Positive Urine Tests for Alcohol, Drugs of Abuse, and Cotinine Among Normal Healthy Research Volunteers (NHRVs): Analysis of Data From 687 NHRVs Screened at a Large Clinical Pharmacology Unit in the United States

“…The criteria for qualification are designed to exclude NHRVs who have characteristics and preexisting conditions that may jeopardize their safety and the utility and adequacy of pharmacokinetic and pharmacodynamic data generated from their participation. 1,2 The major incentive for most NHRVs participating in nontherapeutic early-phase protocols has been shown repeatedly to be monetary, [3][4][5][6][7][8][9] and there is evidence that some of these NHRVs might misrepresent their medical histories to enroll in clinical trials that these participants would not qualify for otherwise. 8,[10][11][12][13] Bentley and Thaker 14 have demonstrated the propensity of NHRVs, when monetary incentives are used, to ''neglect'' to tell researchers about restricted activities they have engaged in either before or during a study, with higher payment levels leading to higher propensity to neglect to tell.…”