Volunteer studies

Evidence for this human health linkage has been suggested from (a) epidemiologic studies of exposed human populations, (b) human volunteer studies, and (c) animal experiments 14). Air pollution levels measured in southwestern Ontario, for instance, have been compared with hospital... 

The critical dose of microorganisms which will irritiate an infection is largely uirknown and varies not only between species but also within a speeies. Animal and human volunteer studies have indicated that the infecting dose m be reduced significantly in the presence of trauma or foreign bodies or if aecompanied by a dmg having a local vasoconstrictive action. 

NoV can spread directly from person to person due to their low infectious dose. Human volunteer studies have estimated that a single infectious NoV particle could cause illness in a susceptible individual (Teunis et ah, 2008). 

There are situations where close-up observations of the volunteer study participant may not be warranted. For example, during a study to determine exposure to pesticides of a group of custom applicators using biological monitoring, observing the workers may not be acceptable in order to make sure that the exposure levels are not biased by any control of the study by the investigator. 

Phase 1 trials are the first in man studies of a new drug in humans. These studies are usually carried out on small samples of subjects. The idea here is to determine the safety of the drug in a small and usually healthy volunteer study population. 

The relationship between exposure and internal dose is known only for a few pyrethroids. Human volunteer studies have shown that, after a single oral administration, pyrethroids and the respective metabolites are excreted in urine within 24 hr and do not accumulate in the body. In field workers exposed to cypermetrin through the dermal route, urine excretion of the intact compound and its metabolites peaked 36 hr after exposure had ceased (WHO, 1989). 

Grattan T, Hickman R, Darby-Dowman A, Hayward M, Boyce M, Warrington S. A five way crossover human volunteer study to compare the pharmacokinetics of paracetamol following oral administration of two commercially available paracetamol tablets and three development tablets containing paracetamol in combination with sodium bicarbonate or calcium carbonate. Eur J Pharm Biopharm 2000 49 225-229. 

The Annex, where physicians had offices and conducted volunteer studies, also had very little visible security. One could often enter it freely through unlocked doors. I remember coming in at night and feeling a spooky Twilight Zone sensation, when walking alone through its deserted halls. 

And expand it did, as the Wolff Committee report evolved into more concrete plans. Major General William Creasy played the role of fundraiser, mesmerizing Congress into believing that war without death might be more than a chemical pipedream. With funds and the go-ahead, volunteer studies began to proliferate. 

The majority of healthy volunteer studies are conducted by contract research organisations (CROs), which recruit subjects from the general public by advertising and word of mouth. The composition of the volunteer database depends to some extent on the location, some being comprised mainly of students or the local residential population, others, particularly in large cities, having a preponderance of backpackers and temporary workers. The source of volunteers does have implications for safety, motivation and withdrawal rates. The more itinerant volunteers may not be available for follow-up and little may be known about their medical background. While the professional volunteer is wholly inappropriate, a stable population of volunteers who understand what is involved... 

Procedures for recruitment of volunteers vary slightly between organisations conducting healthy volunteer studies, but the checklist of procedures provided in Box 4.7 is generic. 

The requirements of GCP, as described in the ICH guidelines, are presented in Chapter 7 and will not be discussed further here. However, it is emphasised that the standards required of large clinical trials in patients apply equally to small clinical pharmacological studies in healthy subjects. Studies should be conducted in accordance with SOPs. Many SOPs will resemble those pertaining to later phase clinical trials, but some will be specific to healthy volunteer studies. Details of procedures not covered by SOPs should be specified in the protocol. Studies must be monitored by the sponsor or a representative the monitor should not be one of the investigators so that monitoring visits and assessments can maintain objectivity. 

The word "tolerability" is perhaps a little clumsy but it describes accurately what is assessed, namely how well the drug is tolerated by those to whom it is administered. This last qualification is necessary because there are many instances in which a drug is better tolerated or less well tolerated by young healthy volunteers than by patients. For example, anxiolytics and tricyclic antidepressants are usually far better tolerated by patients with depression than by healthy volunteers. However, healthy volunteer studies generally provide useful information about tolerability even if it may under- or overestimate tolerability in patients. Many adverse reactions wiU be directly related to the known pharmacological activity of the drug and are therefore predictable. 

Qrme M, Harry J, Routledge P, et al. Healthy volunteer studies in Great Britain the results of a survey into 12 months activity in this field. Br J Clin Pharmacol 1989 27 125-33. 

By contrast, in the population approach, the raw data set that is analysed consists of concentration-time points (and other necessary data such as demographic information) taken from a large number (up to hundreds to thousands) of patients in Phase 11 and/or Phase 111 trials. The number of plasma samples per subject may be sparse but it is possible to estimate the individual pharmacokinetic characteristics of each subject and hence a measure of the mean parameters and their variability can be assessed. Relationships can be sought between patient characteristics (demographics, chnical status) and pharmacokinetic values is found, its consequence may be examined by looking for altered efficacy or safety which may not be possible in a traditional volunteer study. This might lead to demonstration of a therapeutic concentration range. 

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... 

The pharmaceutical industry presents many new challenges to such a person which include the interface with pharmacy and pharmacology, toxicological research, human volunteer studies, clinical trials and post-marketing surveillance to name just a few. Product safety is a factor which impacts on all of those endeavours and the pharmaceutical physician will be expected to work and provide advice within that framework. It will be clear to anyone that evidence of lack of safety in a medical product is not good news for the company concerned and that some level of protective action will often be required which in extreme circumstances may involve product withdrawal. It is, therefore, essential that the pharmaceutical physician should be absolutely clear what constitutes lack of safety in relation to the intended use of the product. 

In view of the regulatory delay that was caused by the need to apply for a CTC, a Statutory Order (SI 1974/498) was made during 1974, to provide an exemption from the need to hold a CTC in such cases, subject to certain conditions. This order applied to trials conducted by doctors and dentists on their own responsibility (DDX). The basis of the clinical trial exemption (CTX) scheme, introduced in 1981, to include studies initiated by the pharmaceutical industry, was that together with a detailed clinical trial protocol and summaries of chemical, pharmaceutical, pharmacological, pharmacokinetic, toxicological and human volunteer studies, a clinical trial in patients may proceed without the need for the additional details normally required for a CTC or Product Licence application. This exemption scheme was based on the requirements that ... 

In the United Kingdom, healthy volunteer studies were subject to self-regulation by the pharmaceutical industry and consequently only the clinical trials in patients had to be covered by a CTC. However, as stated earlier, clinical trials in the UK are now regulated under EU Clinical Trials Directive (2001/20/EEC) fully implemented in the UK. 

The evaluation of the contribution on relative efficacy by cathartic agents to the overall management of oral drug overdoses is often difflcult because of limitations of human volunteer studies that do not simulate clinical conditions, because of multiple therapies employed, because the dosage for cathartics used were not comparable, and because the expected theoretical effects were not observed. 

In a volunteer study in wound care create a wound on each forearm and use dressing of type A on the right forearm and dressing of type B on the left forearm... 

A number of SSRIs and SNRIs were tested for their effects on cognitive function in repeated-dose studies in healthy, non-depressed volunteers. Studies with SSRIs before 1999 have been reviewed by Lane and O Hanlon (1999) and some more recent reports deal with nefazodone. paroxetine and sertraline (Furlan et al., 2001 Schmitt et al., 2001 van Laar et al.. 2002). However, considering the populations studied in these trials (non-depressed subjects), the duration of drug administration (1 2 weeks) and the mostly low drug doses used, the relevance of these studies for a clinical situation may be questioned. 

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