The NIH defines a clinical trial as a prospective biomedical or behavioral research study of human subjects that is designed to answer specific questions about biomedical or behavioral interventions (drugs, nutritional supplements, surgical intervention, or devices). Clinical trials are used to determine whether new biomedical or behavioral interventions are safe, efficacious, and effective. Behavioral clinical trials involving an intervention to modify behavior (diet, physical activity, cognitive therapy, etc.) fit this definition of a clinical trial.

An overview of clinical trials

NIH defines clinical research as: (1) Patient-oriented research. Research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. Patient-oriented research includes: (a) mechanisms of human disease, (b) therapeutic interventions, (c) clinical trials, or (d) development of new technologies. (2) Epidemiologic and behavioral studies. (3) Outcomes research and health.

The birth of the new technologies marks the peak of drug discovery. In our modern society, with rapidly growing technology, we are now able to push research to a level never seen in the past centuries. Hence, biotechnology has given us more tools to understand the insights of the human body and its mechanisms. Everyday, new discoveries bring us closer to a longer and healthier life by giving us the aid to fight diseases, but also to prevent them.

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Human Fetal Lung Fibroblast Cells (MRC-5 Line). These cells were taken using a confocal microscopy . Confocal microscopy allow us to look at specific part of the cells at a high resolution.

In the old days, discovery of drugs often happened by fluke. A good example is the extraordinary discovery of the penicillin by Alexandre Fleming in 1928. A spore from a rare plant (Penicillium) from a mycology lab one floor below drifted in his lab, on a bacterial culture dish, leading to one of the greatest drug discoveries. Nonetheless, if we always had to wait for that type of fortune to happen, discoveries would be extremely rare. Nowadays, new successful drug discoveries depend less on luck and more on the combination of modern benchwork and great science. This is made possible by our more in-depth understanding of the human body and biology combined with more sophisticated tools. In spite of the skyrocketing number of drug discoveries, steps between drug discoveries and their marketing on our drugstore shelves are numerous and often laborious.

Clinical Trial Definition

In search of a new medicine

Clinical trials  (also known as clinical research trials or clinical research studies) study the impact of a drug that is intended to be use in humans on human subjects. Clinical research trials, are part of an important process allowing the collection of data about safety and efficacy before new drugs (including new devices) can be marketed. They are also intended to detect or verify the clinical, pharmacological or pharmacodynamic effect of the drug, identify any adverse event relative to the drug and allow to research other important elements in the comprehension of the drug, such as its distribution and excretion. Clinical research trials can only take place after adequate information have been collected on the product: thorough and promising non-clinical research findings have had to be made first. Consequently, Health Authorities has to approve of them, in the granted country, before any studies on human subjects can start to take place.

Clinical research trials are strictly regulated in every country and follow what are called Good Clinical Practices (GCP), provided by the International Conference on Harmonisation (ICH). GCPs are intended to define a standard in clinical trials across the world and are especially important in the fact that their guidelines include the protection of human rights as a subject in clinical trial, therefore allowing any volunteer that passes the inclusion criteria to join a trial and more importantly, to remove their consent at any given time. They also ensure proper habits and safe practices among the professionals of the industry. Hence, clinical research trials are subjected to international regulations, to regulations specific to each country in which the investigation is conducted, but can also be subjected to regulations specific to a state/province and even to the institution where the study is taking place (ex: hospital).

The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) is a unique project that brings together the regulatory authorities of Europe, Japan and the United States and experts from the pharmaceutical industry in the three regions to discuss scientific and technical aspects of product registration.

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Clinical research trials follow very strict protocols, designed by experts in the domain, and all study investigators must adhere and comply to the given protocol. Any deviations needs to be recorded and authorized by the sponsors.

There are 4 possible phases in clinical trials, which indicate the stage of the product development and each phase can include very distinct elements. Depending on the type of products as well as the stage of the product development, healthy volunteers(controls) or patients can be enrolled. The number of enrolled patients can be increased if and as more positive safety data are collected. The overall number of enrolled volunteers and patients varies for each clinical trial which size also also varies. A trial can be as small as one center in one country or as large as a multicentres trial in multiple countries.

The number of steps between drug discovery and its approval by Health authority for its marketing are fastidious and lengthy. However each step is essential and ensure both efficacy and safety of any new drug. And it is through these trials that investigational drugs, devices and diagnostics may show their benefits.

References:
(1) U.S. Food and Drug Administration (FDA)
(2) Health Canada
(3) Mickey C. Smith (1996), Pharmaceutical Marketing in the 21st century, The Harworth Press

Clinical trial
Clinical trials evaluate the effectiveness and safety of investigational drugs or medical devices by monitoring their effects and efficacy on large groups of people.

Clinical trial centre
Centre or clinic where a clinical trial is taking place.

DNA (deoxyribonucleic acid)
DNA is the hereditary material in humans and almost all other organisms. The most important role of DNA is to store information on a long term basis. DNA can be compared to a set of blueprints, a recipe or a code, because it contains a set of directions that are needed to build components of the cell. While some parts of the DNA carry the genes, our genetic information, other parts DNA serve to regulate the use of the genetic information.

Drugs
In clinical trials and pharmaceutics, the term drug is synonymous with investigational (medicinal)
product, medicinal product, medicine and pharmaceutical product (including vaccines and other biological products).

Drug affinity
The drug affinity measures the ability of the drug to bind to its molecular target.

Drug efficacy
The drug efficacy refers to the ability of a drug-receptor complex to produce a functional response. A drug with high efficacy is also called agonist, in opposition to an antagonist, that has little or no effect.

Drug safety
Drug safety has to be assessed before a drug can be marketed. Drug safety combines the results of animal testing and clinical trials, to evaluate its side effects.
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Drug response
Drug response includes the processes of drug absorption and disposition (e.g.,
pharmacokinetics, (PK), and drug effects (e.g. pharmacodynamics (PD), drug
efficacy and adverse event of drugs).

Ethics
Ethics are the standards that determine the conduct of a person or the members of a profession .

Genomic biomarker
A genomic biomarker is a measurable change in DNA and/or RNA characteristic that suggest a normal biologic processes, a pathogenic (infective) processes, or a response to some form of therapy such as drug interventions is taking place. Genetic biomarkers can include, but are not limited to: expression/function/regulation of a gene, DNA modifications, DNA rearrangements, RNA expression levels, RNA processing.

Good clinical practice (GCP)
GCP is an international quality standard that can be used by governments to regulate any research involving human subjects.

Pharmacokinetics (PK)
PK are the study of processes by which a drug is absorbed, distributed, metabolized, and eliminated by the body.

Pharmacodynamics (PD)
PD are the study of biochemical and physiological effects of drugs on the body and the mechanisms of drug action and the relationship between drug concentration and effect.

Pharmacogenomics (PGx)
PGx is the study of variations of DNA and RNA characteristics and are related to drug responses. PGx are applicable to activities such as drug discovery, drug development, and clinical practice.

Pharmacogenetics (PGt)
PGt is a subset of pharmacogenomics (PGx) and is specific to the study of variations in DNA sequence as related to drug response. PGt are applicable to activities such as drug discovery, drug development, and clinical practice.

Placebo
In a clinical trial setting, a placebo is an inactive substitution given to a subject to compare its effects with those of a real drug. It is suspected that placebo often offer psychological benefits when subjects believe that they are receiving a real treatment.

RNA (ribonucleic acid)
RNA are intermediates between DNA and the cells’ components. They allow the genetic information found in DNA to be built into proteins.

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