Risks and Benefits Tradeoffs

Medical Progress Requires Calculated Risks

Medical progress is based on research, which, in part, depends on experimentation involving people and hazards. Treatments that show acceptable safety profiles and the most promise in laboratory animals are moved into clinical trials involving human volunteers to see if they should be approved for wider use in the general population.

More than three million people annually participate in some 80,000 clinical trials to assess the safety and efficacy of new drugs, treatments, and medical devices. While every effort is made to control risks to clinical trial participants, the experimental nature of these studies makes it impossible to eliminate all risks. Although "new" may imply "better," it is not known whether the potential medical treatment offers benefit to patients until clinical research on that treatment is complete.

“There is no such thing as a 100% safe drug, and as new drugs become more powerful and target more serious illnesses – risks will likely grow, but so will the potential benefits to patients suffering with life-threatening and debilitating diseases. There are no mathematical formulas for making such determinations; decisions are made according to the best judgments of the FDA and the drug sponsors. To date, patients have had only limited involvement in the decision making process, but change may be in the wind.”^[1] The Parkinson’s Pipeline Project is helping to initiate that change.

While clinical trials offer no guarantees, they offer hope when standard treatments fail, or don’t exist.^[1]

Educating patients about necessary risks and building trust between patients and researchers is key to increasing patient participation in research.

Risks and benefits vary with trial type, phase

The risks and benefits of participating in a clinical trial vary from study to study, depending on the type of trial, the procedures and treatments/medicines involved, and the clinical phase of testing. (See Facts About Clinical Trials). Conducted in a progression of phases, each designed to answer new questions and build knowledge about the treatment being studied. Hence, participants in phase 1 trials assume the greatest the risk, and those in phase IV the least.

“Two-thirds (66%) of Americans believe clinical research studies are safe for those who participate,” according to a nationwide survey by The Center for Information and Study on Clinical Research Participation (CISCRP) and Opinion Dynamics Corporation (ODC).^[2] Of the 1,000 adults surveyed in December 2004, “more than half (57%) would have greater trust in clinical research information if the results were made available on a public website or registry.” ^[2]

“As the debate continues about how drug companies and the federal government can best balance the risks and rewards of clinical research while maintaining the public's trust and safety, we will continue to track how this affects their trust and safety, and their perception of clinical research,” said Richard Greif, ODC Project Director.^[3]

FDA: Managing risks of clinical trials

Medical ethics dictate that, “Researchers must never subject research participants to more risk than necessary, be prepared to stop research if it is causing harm, and never put participants at a level of risk disproportionate to the anticipated benefits.”^[3]  A Risk assessment activities identify and characterize the nature, frequency, and severity of risks associated with investigational drug/treatment as it moves through the pipeline. As part of the process, the FDA recommends:

• Carrying out long-term, controlled safety studies including participants of diverse populations.

• Studying the effects of differing doses.

• Watching for potential interactions with other drugs and dietary supplements, product-demographic relationships (e.g. gender, age, and race), and product-disease interactions.

• Following participants to the formal end of the study or beyond to ascertain late safety effects, especially in cases where the drug has a very long half-life, is deposited in an organ such as bone or brain, or has the potential for causing irreversible effects, such as cancer. Follow-up should extend to participants off therapy who drop out of the trial or who finish the study early due to meeting a primary outcome of interest.

• Determining why participants withdraw from studies, and closely following those experiencing serious or significant safety issues until these are permanently resolved.

• Assessing adverse effects involving non-motor complications (e.g. cognitive function, motor skills, sexual function, and mood) often not detected or readily reported by participants, and underestimated or entirely missed by routine adverse event monitoring and safety assessments.

• Seeking input from consumers, pharmacists, physicians, and third party payers. Thus far, FDA consultation with consumers has been limited to patient advisors or sponsors involved with the agency’s special programs for cancer and AIDS. The FDA recently approved the Pipeline Project’s proposal to expand the agency’s Patient Consultant Program to include Parkinson’s disease, paving the way for the Pipeline Project to^[5]

:

• Review study protocol with a patient perspective.

• Evaluate informed consent forms and process.

• Guide participants through the informed consent process.

• Promote good communication between participants and researchers.

• See that participants receive reports of overall study results.

• Ensure protection of participants’ privacy throughout all phases of research.

• Provide patient advocates in clinical settings to make patients feel more comfortable.

Securing approval for public use of new treatment

After the first three clinical trial phases have been completed, the sponsor or researcher applies to the FDA for permission to make the experimental treatment available to the public. The FDA assembles a panel of experts to review the research data. Based on this, the panel will:

• Recommend that the experimental treatment be approved for marketing as it was submitted,

• Require specific changes be made before marketing the experimental treatment, or

• Not approve the experimental treatment due to major problems.

Although not required to do what the expert panel suggests, the FDA usually follows its recommendation.

Clinical trials not subject to FDA regulation are monitored by the sponsoring institution, such as a hospital. (See "Institutional Review Boards")

Sources

1. Benefits vs. Risks: Who Decides?  FDA Consumer magazine, September-October 2003 Issue

2. The Center for Information and Study on Clinical Research Participation (CISCRP) Results of the New National Survey of Public Perception conducted in December 2004

3. National Survey Shows that two-thirds of Americans Think that Clinical Research Studies are Safe ; CISCRP press release 12/23/04

4. Activa Therapy New Hope for Parkinson’s Program Clinical Trials — The Pursuit of Science [12/09; item no longer online]

5. FDA Guidance for Industry – PreMarketing Risk Assessment  

6. National Coalition for PKU & Allied Disorders, Human Subjects Research Protection [12/09; item no longer online]

7. Inside Clinical Trials: Testing Medical Products in People, By Carol Rados
   FDA Consumer magazine September-October 2003 Issue