Clinical Trials for a New Drug Discovery

Written by on August 1, 2017 in Features, Slide - No comments
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Clinical trials are research studies that test how well new medical approaches work in people. Each study answers scientific questions and tries to find better ways to prevent, screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to a treatment that is already available.

Every clinical trial has a protocol, or action plan, for conducting the trial. The plan describes what will be done in the study, how it will be conducted, and why each part of the study is necessary. Each study has its own rules about who can take part. Some studies need volunteers with a certain disease. Some need healthy people. Others want just men or just women.

An Institutional Review Board (IRB) reviews, monitors, and approves many clinical trials. It is an independent committee of physicians, statisticians, and members of the community. Its role is to

  • Make sure that the study is ethical
  • Protect the rights and welfare of the participants
  • Make sure that the risks are reasonable when compared to the potential benefits

In the United States, a clinical trial must have an IRB if it is studying a drug, biological product, or medical device that the Food and Drug Administration (FDA) regulates, or it is funded or carried out by the federal government.

Preclinical Testing

New drugs begin in the laboratory with scientists, including chemists and pharmacologists, who identify cellular and genetic factors that play a role in specific diseases. They search for chemical and biological substances that target these biological markers and are likely to have drug-like effects. Out of every 5,000 new compounds identified during the discovery process, only five are considered safe for testing in human volunteers after preclinical evaluations. After three to six years of further clinical testing in patients, only one of these compounds is ultimately approved as a marketed drug for treatment. The following sequence of research activities begins the process that results in development of new medicines:

  • Target Identification. Drugs usually act on either cellular or genetic chemicals in the body, known as targets, which are believed to be associated with disease. Scientists use a variety of techniques to identify and isolate individual targets to learn more about their functions and how they influence disease. Compounds are then identified that have various interactions with the drug targets that might be helpful in treatment of a specific disease.
  • Target Prioritization/Validation. To select targets most likely to be useful in the development of new treatments for disease, researchers analyze and compare each drug target to others based on their association with a specific disease and their ability to regulate biological and chemical compounds in the body. Tests are conducted to confirm that interactions with the drug target are associated with a desired change in the behavior of diseased cells. Research scientists can then identify compounds that have an effect on the target selected.
  • Lead Identification. A lead compound or substance is one that is believed to have potential to treat disease. Laboratory scientists can compare known substances with new compounds to determine their likelihood of success. Leads are sometimes developed as collections, or libraries, of individual molecules that possess properties needed in a new drug. Testing is then done on each of these molecules to confirm its effect on the drug target.
  • Lead Optimization. Lead optimization compares the properties of various lead compounds and provides information to help biopharmaceutical companies select the compound or compounds with the greatest potential to be developed into safe and effective medicines. Often during this same stage of development, lead prioritization studies are conducted in living organisms (in vivo) and in cells in the test tube (in vitro) to compare various lead compounds and how they are metabolized and affect the body.
Three Phases of Clinical Trial

Most clinical research that involves the testing of a new treatment progresses in phases. This allows researchers to ask and answer questions in a way that yields reliable information about the treatment and protects the patients.

Clinical trials are usually classified into one of three phases:

  1. Phase I Trials are the first step in testing a new treatment in humans. In these studies, researchers may evaluate how a new drug should be given (by mouth, injected into the blood, or injected into the muscle), how often, and what dose is safe. A phase I trial usually enrolls only a small number of patients, sometimes as few as a dozen. About 70 percent of experimental drugs pass this initial phase of testing.
  2. Phase II Trials focus on evaluating how well the new treatment works. They also continue to test the safety of the treatment. This second phase of testing may last from several months to two years, and involves up to several hundred patients. About one-third of experimental drugs successfully complete both phase I and phase II studies.
  3. Phase III Trials compare the results of people taking the new treatment with results of people taking standard treatment. Investigators usually assign participants to the standard treatment group or the new treatment group at random (called randomization). Phase III trials often enroll large numbers of people and may be conducted at many doctors’ offices, clinics, and health centers nationwide.
The Length of Clinical Trials

Clinical trials can take several years to complete. Some possible reasons are:

  • For chronic conditions such as cancer, it takes months, if not years, to see if a cancer treatment has an effect on a patient.
  • For drugs that are not expected to have a strong effect (meaning a large number of patients must be recruited to observe ‘any’ effect), recruiting enough patients to test the drug’s effectiveness (i.e., getting statistical power) can take several years.
  • Only certain people who have the target disease condition are eligible to take part in each clinical trial. Researchers who treat these particular patients must participate in the trial. Then they must identify the desirable patients and obtain consent from them or their families to take part in the trial.

The biggest barrier to completing studies is the shortage of people who take part. All drug and many device trials target a subset of the population, meaning not everyone can participate. Some drug trials require patients to have unusual combinations of disease characteristics. It is a challenge to find the appropriate patients and obtain their consent, especially when they may receive no direct benefit (because they are not paid, the study drug is not yet proven to work, or the patient may receive a placebo). In the case of cancer patients, fewer than 5% of adults with cancer will participate in drug trials.

Source: https://medlineplus.gov/clinicaltrials.html

By Thomas Hibbard
Creative Director, Med Monthly

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