Clinical Trial Information

Clinical trials are organized research studies that test the effects of specific medical approaches in people. The trials help to determine better approaches for disease prevention, screening, diagnosis, and treatment. Clinical trials are conducted only after successful initial laboratory studies and animal studies are conducted. Trials are sponsored by a variety of individuals and organizations, including researchers and physicians, academic medical centers, pharmaceutical companies, and government agencies.

Participating in a clinical trial

Some people choose to join a clinical trial so they can play a more active role in their own health care and to help others by contributing to research. Sometimes participation in a study can require extra time and effort (eg, doctor visits or hospital stays). When considering the pros and cons of participating, it can be helpful to talk to your doctor, family, and friends.

All clinical trials have requirements for who can participate in the study (inclusion criteria) and who cannot (exclusion criteria). These criteria are based on factors such as age, gender, type and stage of disease, medical history, laboratory test results, and other factors. Depending on the stage of testing, some studies enroll patients with illnesses while other studies seek healthy individuals. Typically, studies of rare diseases enroll patients rather than healthy volunteers.

An overview of the 4 phases of clinical trials is provided below.
Overview of the phases of clinical trials
Phase I Phase II Phase III Phase IV
  • Initial stage for testing an experimental treatment in humans
  • Usually enrolls 20 to 80 healthy volunteers1; however, actual patients are often enrolled in trials of rare or chronic diseases (when other treatment options are not available)
  • Examines initial effects and safety
  • Evalates the safety of increasing doses
  • Assesses how the drug interacts with the body (pharmacokinetics and pharmacodynamics)
  • May provide preliminary evidence of effectiveness
  • Second stage for testing an experimental treatment in humans
  • Usually enrolls patients and in larger numbers than Phase I.1
  • Evaluates initial efficacy
  • Continues safety assessments from Phase I
  • Phase IIA studies dosing requirements; Phase IIB studies efficacy
  • Some trials combine Phases I and II
  • Third stage for testing an experimental treatment in humans
  • Randomized, controlled, multicenter trials* in larger numbers, sometimes more than a thousand patients.
  • Confirms the effectiveness of the product and general safety (versus a placebo or another treatment).
  • Two or more successful Phase III trials are typically required for regulatory approval of a treatment
  • Fourth stage of evaluation of drugs. Phase IV studies occur following the regulatory approval of the treatment.
  • Collects additional evidence on risks and benefits
* A randomized trial is one in which study participants are randomly assigned to different treatment groups. A controlled trial is one in which one group receives a "control" treatment—such as a placebo (an inactive substance) or another medicine or medical intervention—to allow comparison with the group receiving the test treatment under evaluation. A multicenter trial is one that is conducted at multiple study locations.
Reference
  1. ClinicalTrials.gov Web site. Understanding clinical trials. http://clinicaltrials.gov/ct2/info/understand. Accessed March 31, 2009.

Clinical trials for rare diseases

Clinical trials study important research questions, follow careful methods to ensure accurate results, and respect ethics that minimize risks to people. Whenever possible, clinical trials use standard trial designs and large sample sizes (numbers of study participants). This helps to ensure adequate statistical power for detecting treatment benefits and risks.

In clinical trials for rare diseases, however, the sample size is unavoidably small, requiring innovative approaches to optimizing the study design and data analysis. Here are some ways that clinical trials for rare diseases differ from clinical trials for other conditions.

  • Use of patients instead of healthy volunteers during Phase I. Phase I clinical trials for rare diseases often enroll patients with the targeted disease rather than healthy volunteers. Commonly, other treatment options are not available for patients with rare diseases.
  • Fewer patients. In all phases of clinical trials, the number of patients required for studying rare diseases is much lower than for other diseases. For example, whereas a Phase III study of a common disease such as diabetes may enroll thousands of patients, a late-phase study of a rare disease may include fewer than 100 patients. When study results are analyzed, the small sample size in rare-disease trials can make it challenging to prove true treatment effects. Study design and statistical methods used in larger clinical trials to ensure reliable results (for example, inclusion and exclusion criteria, randomization, and results analyses) may be less useful in small trials.
  • Statistical power and generalizablwww.nlm.nih.gov/medlineplus/tutorials/cancerclinicaltrials/htm/index.htme results. Typically, the statistical power of a study—and the reliability of the results—increases as the number of study participants increases. Also, well-conducted larger studies typically produce more generalizable results, meaning that the results would also be expected in similar patients who did not participate in the study. Small patient populations can present study design challenges for clinical trials of rare diseases.
  • Combined phases. In clinical trials for rare diseases, the phases are sometimes combined, such as Phase I/II or Phase II/III, in order to maintain enrollment of the relatively small number of patients and expedite progression of all phases of the study program. Historically, the approval time for orphan drugs (the only available drugs to treat rare diseases) has been considerably shorter than for other drugs. Many orphan products receive expedited review or accelerated approval because they are for a serious or life-threatening disease.1
  • Efficacy versus placebo within a specific time frame. Rare disease clinical trials must prove that the product is more efficacious than placebo within a specific time frame, which can sometimes be a challenge in a population with a rare genetic disease. As a result, study inclusion criteria may be strict in order to ensure the best chance for success.

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References
  1. US Food and Drug Administration Web site. OOPD Frequently Asked Questions. http://www.fda.gov/orphan/faq/index.htm. Accessed April 6, 2009.

Finding clinical trials on ClinicalTrials.gov

If you are interested in knowing about ongoing clinical trials, the website ClinicalTrials.gov provides regularly updated information about thousands of federally and privately supported clinical trials. You can find clinical trials for a wide range of diseases and conditions, including rare diseases. Each clinical trial listed on the website includes the following information:

  • Disease or condition and experimental treatments studied
  • Title, description, and design of study
  • Requirements for participation
  • Locations where the study is available
  • Contact information

To find clinical trials of interest to you, you can visit the ClinicalTrials.gov website at http://clinicaltrials.gov, or visit their helpful how-to page "Help for Searching ClinicalTrials.gov" at http://clinicaltrials.gov/ct2/help/help.