Non-patient volunteers

The Association of the British Pharmaceutical Industry. Guidelines for the Facilities in Which Studies on Non-patient Volunteers are Conducted. London ABPl, 1989. 

Where Phase II, III and IV studies are conducted in a hospital or contract research environment, it is strongly advisable to inform the subject s general practitioner (GP) in writing of the nature of the study and to obtain the GP s agreement, preferably in writing. This is essential for Phase 1 studies in non-patient volunteers, and it is routine practice in all Phase 1 clinical pharmacology units. However, increasingly, particularly in mainland Europe, study subjects will be found not to have a personal physician or, if they have, that their last visit to the physician could be a considerable time ago. 

This section aims to provide sufficient information for the pharmaceutical physician to effectively prepare and support a clinical trial. However, clinical trials come in many forms and what is appropriate for a single-centre non-sponsored trial is totally inappropriate for a multicentre global study sponsored by a big pharmaceutical company or institution. Similarly, a Phase 1 non-patient volunteer study... 

ABPI. Medical experiments in non-patient volunteer studies. Available at http //www.abpi.org.uk. 

At the time of writing, the conduct of studies in non-patient volunteers in the UK is not regulated by the Medicines Act (1968). Similarly, studies in non-patient volunteers in the Netherlands, Belgium and some other European countries do not require regulatory approval. This situation is about to change, as the EU Directive issued in 2001 will require to be implemented in all European countries by 2004. All healthy volunteer studies will then require regulatory approval in addition to that of an ethics committee. The Directive, with which all member states must comply, makes no distinction between healthy volunteer studies and clinical trials in patients who may benefit from treatment. However, the precise details of documentation required for authorisation of healthy volunteer studies may vary from country to country it is possible that the application in the UK will be somewhat less detailed than the current Clinical Trials Exemption. 

Lacey JH, Mitchell-Heggs P, Montgomery D, et al. Guidelines for medical experiments on non-patient human volunteers over the age of 65 years. J Pharm Med 1991 1 281-8. The Association of the British Pharmaceutical Industry. Guidelines for the Eacilities in Which Studies on Non-Patient Volunteers are Conducted. London / BPI, 1989. 

Phase I. Clinical pharmacology in small numbers (tens) of healthy non-patient (or patient) volunteers to assess tolerability, preliminary safety, pharmacokinetics, and pharmacod)mam-ics where practicable [i.e. biological effect using surrogate endpoints (see Section 6.6.5.1) or, rarely, therapeutic effect]. 

The importance of adenosine deaminase in the duration and intensity of sleep in humans has been noted recently (Retey et al. 2005). Animal studies suggest that sleep needs are genetically controlled, and this also seems to apply in humans. Probably, a genetic variant of adenosine deaminase, which is associated with the reduced metabolism of adenosine to inosine, specifically enhances deep sleep and slow wave activity during sleep. Thus low activity of the catabolic enzyme for adenosine results in elevated adenosine, and deep sleep. In contrast, insomnia patients could have a distinct polymorphism of more active adenosine deaminase resulting in less adenosine accumulation, insomnia, and a low threshold for anxiety. This could also explain interindividual differences in anxiety symptoms after caffeine intake in healthy volunteers. This could affect the EEG during sleep and wakefulness in a non-state-specific manner. 

In this section, a brief summary of the nature, frequency, and consequences of adverse drug reactions (ADRs) in two clinical situations is presented. There are ADRs experienced by healthy volunteers and patients participating in clinical studies with potential new medicines and those experienced by patients who are prescribed licensed medicines. A review of these two situations points to areas of success with the current practices for non-clinical safety pharmacology testing but also identifies some areas where further research might lead to new or better safety pharmacology tests. Prior to reviewing the literature, some... 

P MRS in several human cancers, including non-Hodgkin s lymphoma (NHL), sarcomas of soft tissue and bone, breast cancer, and head and neck cancerInitially, they showed basic technique reproducibility in vitro and for quadriceps muscle in volunteers across participating institutions. Spectral quality and reproducibility varied among the different cancers. Later, they demonstrated that a reproducible measure of PME normalized to nucleoside-triphosphate resonances could be obtained for a select group of matched patients with NHL. ... 

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