About Clinical Trials
Drug Evaluation Process
Vitamin Intake Recommendations

What is a clinical trial or clinically-based research?

A clinical trial (also called clinical research) is a research study in humans to answer specific questions. Carefully conducted clinical trials are the fastest and safest way to find treatments that work in people and ways to improve health. Interventional trials determine whether experimental treatments (medications, procedures, or behavioral interventions) or new ways of using known therapies are safe and effective under controlled environments. Observational trials address health issues in large groups of people or populations in natural settings. (These are often called epidemiologic studies.)

What are the benefits and risks of participating in a clinical trial?

Benefits. Clinical trials that are well-designed and well-executed are the best approach for eligible participants to:

• Play an active role in their own health care.
• Gain access to new research treatments before they are widely available.
• Obtain expert medical care at leading health care facilities during the trial.
• Help others by contributing to medical research.
  

Risks. There are risks to clinical trials and they vary with the specifics of the trial.

• There may be unpleasant, serious or even life-threatening side-effects to treatment.
• The treatment may not be effective for the individual participant.
• Participation in the study follows a specific protocol of visits, testing, or procedures that may require more time and attention than would a non-protocol treatment, including trips to the study site, more treatments, hospital stays or complex dosage requirements.
  What should people consider before participating in a trial?
• People should know as much as possible about the clinical trial and feel comfortable asking the members of the healthcare team questions about it, the care expected while in a trial, and the cost of the trial.

The Evaluation of Pharmacologic Therapy in Humans: A Brief Summary of the Drug Evaluation Process in the United States
—Janice B. Schwartz, M.D.

In the United States, approval of a new drug for clinical use follows a series of developmental and evaluative steps under an Investigational New Drug (IND) Application, which precedes submission of a New Drug Application (NDA) for marketing approval from the Food and Drug Administration (FDA). The process is divided into preclinical and three clinical, investigational phases followed by NDA review by the FDA.

Preclinical Studies

Preclinical studies are usually performed in animals to address biological activity, toxicity, and safety data, and collection of medication concentration and effect data to assist in developing initial human dosing regimens.

Clinical Studies

Phase I studies are performed in healthy volunteers and patients to define initial toxicity parameters, the tolerated dose range, how the medication appears and distributes through the body, how it is removed from the body, and the effects of the medication on humans. Special patient target populations may be evaluated, and different methods of drug formulation or delivery systems may be tested (usual, n = 20-80).

Phase II studies test clinical efficacy or therapeutic effectiveness, and are designed to provide dose/concentration versus response relationships in closely monitored patient groups of limited numbers (usual, n = 100-200). Results aid in the design of studies in phase III.

Phase III studies are patient studies that document clinical safety and efficacy, further refine the dose/concentration versus response relationships, and assess adverse drug reaction rates. Larger numbers of patients are usually studied in phase III (usual, n = a few hundred to thousands) than in phase II; however, phase II and phase III studies often go on simultaneously.

Phase IV trials are postmarketing approval surveillance trials, and are variable in design and objective.

From: Schwartz, JB. Pharmacy Focus. The evaluation of pharmacologic therapy in humans: a brief summary of the drug evaluation process and guidelines for clinical trials as they relate to women. J Gender-specific Medicine 2001; 4(4), 13-17

Vitamin Intake, Recommended Intake and Gender Differences
—Janice B. Schwartz, M.D.

Vitamins are essential to life. Diseases such as scurvy occur when vitamin C intake is inadequate; bone disease such as rickets or osteoporosis occur when vitamin D intake is inadequate; anemias occur when vitamin B levels are inadequate; deficiency of folic acid during pregnancy can lead to fetal neural tube defects; and bleeding disorders occur when vitamin K levels or intake are inadequate.

Recently, daily dietary vitamin supplementation has been promoted for contributing to good health as well as to prevent disease. Scientific evidence to support many of the purported health benefits for dietary vitamin supplementation of a balanced diet is limited or non-existent.

Not everyone needs or ingests the same amount of food or liquid intake every day. There is overwhelming information from scientific investigations and clinical experience that demonstrates the needs for different doses of therapeutic medications for people of different ages, sizes, race, sex, diseases, and those taking combinations of medicines and eating different diets. One would therefore expect both the daily vitamin intake from food, and the total daily vitamin requirements to differ between individuals.

Daily iron and folate intake should be higher in menstruating women than men of similar age, while lower total intake of vitamins A, B, E, K, and zinc are based on body size and usually lower in women compared to men. Adequate daily intake can be achieved through a balanced diet for most nutrients and vitamins. Exceptions are the need for the supplementation of most vitamins and folate in pregnant women, and for vitamin D and calcium in older individuals.

From Schwartz, JB. Pharmacy Focus. Vitamin Intake, recommended intake, and gender differences. J Gender-specific Medicine 2001; 4(1), 11-15.