Clinical Research

‘…step out of the failing ‘regulatory driven’ approach and use a more ‘scientifically driven’ program…’
R. Colin Garner, CEO Xceleron

Clinical research is a systematic measure used to assess safety and efficacy of new medicines in human subjects. Such studies compare the new treatment under evaluation with a placebo or a previous standard treatment.

 Clinical research (e.g. for human testing or human experimentation) is carried out in publicly-funded hospitals or privately-owned contract research organizations under the supervision of a medical staff called investigators. The purpose is to assess a new drug or procedure that seems to be promising based on previous tests performed on several animal species (mostly rats, dogs and monkeys). However, successful results in animals never provide evidence that the same results will occur in the human species. In practice, 40% of new compounds entering clinical testing fail because of improper pharmacokinetics derived from animal studies.

There are different types of research on human subjects depending on the purpose of the investigation. There are treatment trials in which a new treatment is compared with current treatment or a placebo (i.e. a sugar pill with no therapeutic effect).

For example, in order to assess the safety and effectiveness of COX-2 inhibitors (VIOXX) one set of patients was given the drug while another set of randomly selected patients was given aspirin, which is effective to relieve pain in patients suffering from arthritis but causes serious side effects (e.g. bleeding ulcers). The hypothesis that COX-2 inhibitors could offer pain relief without the side effect of aspirin was thus evaluated.

Prevention trials seek whether a treatment or a change of lifestyle can prevent a disease. For example, researchers had found that administration of selenium over several years could reduce the rate of prostate cancer. Similarly, the Breast Cancer Prevention Trial (BCPT), which included women at increased risk for breast cancer, demonstrated the value of the drug tamoxifen in reducing the incidence of the disease in this population. These are typical examples of such prevention trials.

In addition, diagnosis trials enable doctors to evaluate quickly a diagnosis through the use of new screening tests. The benefits of this approach have been demonstrated with the use of magnetic resonance imaging to diagnose multiple sclerosis, and other neurological problems, as well as the use of screening tests to identify malign cells in cancer patients.

The duration of clinical trials can range from very short (a few weeks) to very long (a lifetime) in the case of chronic conditions. Often, patients are asked to fill questionnaires and surveys to measure the incidence of several factors on the onset, course, and term of the disease.

A clinical research has several phases. Phase I studies are performed in a small group of volunteers, who agreed to participate, to assess the safety of a new product, and to determine the dose range and any possible side effects. These studies are very closely monitored, for the new compound has never been tested in the human species. Up to this point, researchers have had to rely on animal data, which can be either confirmed, or more commonly, invalidated during Phase I clinical trial. Let’s keep in mind that 80% of clinical trials are uninformative and virtually all trials of a new drug are based on pre-clinical animal research.

Phase II studies involve from 100 to 300 volunteers over a longer period of time. In short, they are important to measure both safety and effectiveness.

Phase III studies require the participation of thousands of volunteers and may last for more than a year. The objective is to gather enough information that will serve to prove to the health authorities (Health Canada , FDA) that the benefits outweigh the risks and that further studies are necessary to examine more precisely the side effects and therapeutic value, compared to current therapy or placebo.

Finally, phase IV studies occur after the drug is on the market. The aim is surveillance; a drug may cause unpredicted side effects or have a dubious effectiveness that could not be observed in a rather small and restrictive sample of the population (i.e., white adult men). These studies also provide the opportunity to observe how the drug acts in a real-life environment where patients behave differently than in-bred, genetically identical rats or mouse, that live in an aseptic environment and artificial environment. As of today in the USA , legal drugs kill more people than illegal drugs and this phenomenon has become the third cause of mortality. Five major reasons are listed below:

1) Many unsafe and/or ineffective drugs are rubber-stamped by health authorities under corporate pressure

2) Multiple prescriptions are given to patients, especially the elderly, resulting in poor treatment compliance, drug-drug interactions and poisoning

3) Reliance on animal tests is pervasive to support human medicine

4) Poor clinical trials are conducted resulting in biased or counterfeit clinical data

5) Insufficient post-marketing surveillance of new drugs

The Ethics of Research on Human Subjects.

The Concept of Micro Dosing.