The development of a new drug is a long and complicated journey. The role of the doctors, nurses, and other support staff is a critical one. Most of the drugs in use today have, after their initial discovery, undergone a range of laboratory tests using cell cultures, isolated tissues, and animals. If a drug shows clinical potential, it may be used in humans only after successful completion of pre-clinical toxicity tests on different animal species. For the 50,000 or so substances which are synthesized in the laboratory, approximately five will reach the stage of full tests in humans-only one of these will actually be safe and effective enough to be marketed.
After much of the laboratory testing is completed, the first use of the drug in humans can take place. The tests on humans can generally be classified into four phases:
Phase Iare normally done in healthy volunteers, usually in special hospital units equipped for performing these trials. Studies on the drug’s absorption, distribution, metabolism, and excretion (pharmacokinetics) are done.
Phase IIare generally the first trials in patients, conducted to mainly give an idea of efficacy, to identify the optimal dose, and to provide the first indication on safety in patients. Up to a few hundred patients are involved in this phase.
Phase IIIare the main assessment of safety and efficacy of a drug. Many more patients are treated in phase III trials-up to several thousands.
Phase IVare those performed after obtaining a license to market the drug. Contrary to Phases II and III, problems associated with long term use of the drug or rare adverse events can be detected.
The basic principles of GCP (Good Clinical Practice) are first for the protection of the research patient or volunteer and second to collect data that can be replicated and is correct. One of the reasons that GCP was introduced and accepted was because of concern about drug safety. In particular there was public anxiety among regulators about the quality and reliability of the research data submitted to regulatory authorities. Fraudulent data could jeopardize patient safety or could cause rejection of an application for a new drug with potential for curing illness. Fraudulent data usually emphasized the efficacy and underplayed the toxicity of a drug.
Pharmaceutical companies around the world are engaged in more research now than ever in the history of medicine. It is through the research process that new treatments are discovered to treat illnesses. Without research, many diseases that have been controlled, or have been cured would still plague the world.
Various government agencies are charged with regulating medications, medical devices, and medical treatments. The primary goals of this regulation are to make sure that the medications available in the United States are both safe and effective in the treatment of particular illnesses. At times, research also looks into new uses for medications that are currently available by prescription, or investigate the possibility of medications being made available without prescription. Other areas of research include Pharmacoeconomics which is the science of looking at the cost of medications, and the worth of that expense to society.
Research is conducted in a number of different settings. Universities, government agencies, and research centers are a few of these research settings. The National Institutes of Health, the Food and Drug Administration (FDA), private foundations, and pharmaceutical companies, as well as other branches of industry and government may request or sponsor research.
All participants in clinical trials are volunteers. For some types of studies, participants for a study who are healthy, and not suffering from any current illness are recruited. These studies are largely for the purpose of investigating the metabolism of a drug. There is often no therapeutic benefit to those participants other than contributing to medical science, and on some occasions a payment for their time and assistance. For most studies, participants must be diagnosed with a specific illness or disease. A physician or other licensed professionals will take a detailed history, perform a physical examination, and review laboratory tests to make sure that the diagnosis is correct, and that no other illness will confound the results of the study, or endanger the patient’s health or safety. Volunteers come to the clinic from a variety of sources including physician and hospital referral, referral by previous study participants, and response to an advertisement or other public notices.
Before a medication or treatment can be used in a general medical practice, it has to be proven to be safe in a laboratory or research clinic setting. Before a volunteer begins participation in a research study, the potential risks and side effects of the experimental medication are explained to them in detail. The participant signs a consent form that reviews the study design, and the safety and efficacy profile of the medication being studied. The research itself is conducted under the supervision of a physician and their staff, and a medical monitor from the sponsoring agency, organization or from the pharmaceutical company.
All participants in a clinical research study have a medical chart at the Research Company. This includes the results of the initial history and physical examination, laboratory tests, cardiograms, and the results of any other medical procedures. Upon request, these records can be sent to your own physician for inclusion in your permanent record.
For each study, a copy of the experimental protocol, and complete information about the medication is reviewed by an independent investigational review board (IRB) or ethics committee. No volunteers can be entered into a research study before this committee has approved of the research protocol, the advertisements for the research, and the consent form that explains the research to the participant.
Payment for participation in clinical trials varies according to the research project, medication, disease under investigation, and “phase” in the development cycle of the study. Often the cost of transportation will be reimbursed. For phase I and early phase II studies, where there is no long-term therapeutic benefits to participants, often compensation is given for the time involved, and any discomfort caused by the experimental procedures.
For a medication to be shown effective, it has to be compared with an inactive substance or placebo medication. If it is no better than the placebo, the conclusion from the research is that it doesn’t work. In addition, experimental medications are often compared against a marketed compound. To be a useful medication, it should be as effective as medication currently on the market, and better than placebo. Interestingly, 30-40% of volunteers who take placebo medication get relief of their symptoms.
Because volunteers have been diagnosed with an illness or disease, at the end of their participation, follow-up medical care is often provided. This service includes follow up visits with the physician, or someone on their staff, and in some cases, medication for three months. We then refer patients back to their regular physicians, with recommendations for treatment.
Informed consent is the process designed to give volunteers the information that they need to decide about participating in a clinical study. This process allows the volunteer to ask questions and to exchange information freely with the clinical investigator. The clinical investigator is responsible for ensuring that informed consent is obtained from each research volunteer before that person participates in the research study.
The IRB is a group of healthcare professionals and non-scientific members which must review and approve a clinical study before it begins. The IRB carefully reviews study activities because its primary responsibility is to protect the safety and rights of study participants.