Thousands of years ago, ancient peoples attributed pain to spirits and treated it with mysticism and incantations. Over the centuries, science has provided us with a remarkable ability to understand and control pain with medications, surgery, and other alternative and complementary treatments. Today, scientists understand a great deal about the causes and mechanisms of pain, and research has produced dramatic improvements in the diagnosis and treatment of a number of painful disorders. For people who fight every day against the limitations imposed by pain, the work of National Institutes of Health. National Institute of Neurological Disorders and Stroke (NINDS)-supported scientists holds the promise of an even greater understanding of pain in the coming years. Their research offers a powerful weapon in the battle to prolong and improve the lives of people with pain: hope.i National Institutes of Health. National Institute of Neurological Disorders and Stroke. “Pain: Hope Through Research.” http://www.ninds.nih.gov/disorders/chronic_pain/de
tail_chronic_pain.htm#175133084. Accessed May 30, 2012.

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A clinical trial (also called clinical research) is a research study in human volunteers to answer specific health 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 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.

Who Can Participate in Clinical Trials?

All clinical trials have guidelines about who can participate. Inclusion/exclusion criteria are the medical or social standards determining whether a person may or may not be allowed to enter a clinical trial. These criteria are based on such factors as age, gender, the type and stage of a disease, previous treatment history, and other medical conditions. It is important to note that inclusion and exclusion criteria are not used to reject people personally, but rather to identify appropriate participants and keep them safe. Inclusion/exclusion criteria, which will vary by study, are an important principle of medical research that helps to produce reliable results. The factors that allow someone to participate in a clinical trial are called “inclusion criteria” and those that disallow someone from participating are called “exclusion criteria.”

Before joining a clinical trial, a participant must qualify for the study. Some research studies seek participants with illnesses or conditions to be studied in the clinical trial, while others need healthy participants. The inclusion/exclusion criteria help ensure that researchers will be able to answer the questions they plan to study.

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People participate in clinical research for a variety of reasons. People who volunteer for phase II and phase III trials can gain access to promising drugs long before these compounds are approved for the marketplace. (See information on the different phases of clinical trials below.) They typically will get excellent care from the physicians during the course of the study. This care also may be free.

The patient’s rights and safety are protected in two important ways. First, any physician awarded a research grant by a pharmaceutical company or the National Institutes of Health (NIH) must obtain approval to conduct the study from an Institutional Review Board (IRB). The review board, which is usually composed of physicians and lay people, is charged with examining the study’s protocol to ensure that the patient’s rights are protected, and that the study does not present an undue or unnecessary risk to the patient. Second, anyone participating in a clinical trial in the United States is required to sign an “informed consent” form. This form details the nature of the study, the risks involved, and what may happen to a patient in the study. The informed consent tells patients that they have a right to leave the study at any time.

Patients considering participating in clinical research should talk about it with their health care professionals and medical caregivers. They also should seek to understand the credentials and experience of the individuals and the facility involved in conducting the study.iiCenterWatch.“Volunteering for a Clinical Trial,” http://www.centerwatch.com/clinical-trials/volunte
ering.aspx, Accessed May 30, 2012.

Other questions to ask include:

• How long will the trial last?

• Where is the trial being conducted?

• What treatments will be used and how?

• What is the main purpose of the trial?

• How will patient safety be monitored?

• Are there any risks involved?

• What are the possible benefits?

• What are the alternative treatments besides the one being tested in the trial?

• Who is sponsoring the trial?

• Do I have to pay for any part of the trial?

• What happens if I am harmed by the trial?

• Can I opt to remain on this treatment, even after termination of the trial?

More information can be found at CenterWatch – Volunteering for a Clinical Trial.

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The clinical trial team includes doctors and nurses, and may also include social workers, pharmacists, and other health care professionals. They check the health of the participant at the beginning of the trial, give specific instructions for participating in the trial, monitor the participant carefully during the trial, and stay in touch after the trial is completed. The clinical trial process depends on the kind of trial being conducted. Different types of clinical trials include:iiiClinical Trials.Gov. http://clinicaltrials.gov/ct2/info/understand#type
s, Accessed May 30, 2012

• Treatment trials test experimental treatments, new combinations of medications, or new approaches to surgery or radiation therapy.

• Prevention trials look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include medicines, vaccines, vitamins, minerals, or lifestyle changes.

• Diagnostic trials are conducted to find better tests or procedures for diagnosing a particular disease or condition.

• Screening trials test the best way to detect certain diseases or health conditions.

• Quality of Life trials (or Supportive Care trials) explore ways to improve comfort and the quality of life for individuals with a chronic illness.

A video outlining the steps of a clinical trial and drug discovery process can be viewed here.

What are the Phases of Clinical Trials?

Clinical trials are conducted in phases. The trials at each phase have a different purpose and help scientists answer different questions.iiiClinical Trials.Gov. http://clinicaltrials.gov/ct2/info/understand#type
s, Accessed May 30, 2012

• In Phase I trials, researchers test an experimental drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

• In Phase II trials, the experimental study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

• In Phase III trials, the experimental study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely.

• In Phase IV trials, post marketing studies delineate additional information including the drug’s risks, benefits, and optimal use.

Some clinical trials involve more tests and doctor visits than the participant would normally have for an illness or condition. For all types of trials, the participant works with a research team. Clinical trial participation is most successful when the protocol is carefully followed and there is frequent contact with the research staff. A protocol is a study plan on which all clinical trials are based. The plan is carefully designed to safeguard the health of the participants as well as answer specific research questions. A protocol describes what types of people may participate in the trial; the schedule of tests, procedures, medications, and dosages; and the length of the study. While in a clinical trial, participants following a protocol are seen regularly by the research staff to monitor their health and to determine the safety and effectiveness of their treatment.

What is Informed Consent?

Informed consent is the process of learning the key facts about a clinical trial before deciding whether or not to participate. It is also a continuing process throughout the study to provide information for participants. To help someone decide whether or not to participate, the doctors and nurses involved in the trial explain the details of the study. If the participant’s native language is not English, translation assistance can be provided. Then the research team provides an informed consent document that includes details about the study, such as its purpose, duration, required procedures, and key contacts. Risks and potential benefits are explained in the informed consent document. The participant then decides whether or not to sign the document. Informed consent is not a contract, and the participant may withdraw from the trial at any time.iiCenterWatch. “Volunteering for a Clinical Trial,” http://www.centerwatch.com/clinical-trials/volunte
ering.aspx, Accessed May 30, 2012.

More information about informed consent can be found at CenterWatch, Volunteering for a Clinical Trial.

Why is it Important to Participate in Clinical Trials?

To make better progress against a disease or illness, more patients must enroll in clinical trials. There’s an abundance of rationally designed promising new agents, which need to be tested as single agents, but also with existing protocols. However, the pool of patients considering clinical trials remains very low, therefore studies failing to reach enrollment goals are increasing as the number of promising agents increase.ivPatients Against Lymphoma, Patient Participation in Clinical Trials. http://www.lymphomation.org/clinical-trials-partic
ipation.htm. Accessed May 30, 2012.

One study of National Cancer Institute (NCI)-designated Comprehensive Cancer centers showed that nearly 60% of trials opened for 5 years had fewer than five patients enrolled at each site, and, for more than 20% of studies, not a single subject had been accrued. Looking at the bigger picture, of all NCI phase I, II, and III trials opened and closed between 2000 and 2007, only 50%–60% achieved minimal stated accrual goals. So, while perhaps only one in five cancer clinical trials is ever published, of those unpublished, a significant percentage probably died for lack of accrual.vCurt G. et al “One in Five Cancer Clinical Trials is Published: A Terrible Symptom – What’s the Diagnosis?” The Oncologist. 2008 Sept:13(9)923-924.  

Slow enrollment of patients delays the evaluation of drugs, contributes to costs, and raises the financial risks of developing new drugs – but most importantly, delays cost lives.

BenefitsiiiClinical Trials.Gov.http://clinicaltrials.gov/ct2/info/understand#type
s, Accessed May 30, 2012

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.

• There may be unpleasant, serious or even life-threatening side effects to experimental treatment.

• The experimental treatment may not be effective for the participant.

• The protocol may require more of their time and attention than would a non-protocol treatment, including trips to the study site, more treatments, hospital stays or complex dosage requirements.

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It is important to understand the reasons why so few adults participate in clinical trials. For example, the National Cancer Institute provides some reasons why adults do not participate in cancer trials.viNational Cancer Institute. “Cancer Clinical Trials: A Resource Guide for Outreach, Education, and Advocacy.” NIH Publication No. 02-5053.  September 2002. http://www.cancer.gov/clinicaltrials/education/out
reach-education-advocacy/ResourceGuide_Book_m.pdf  Accessed May 30, 2012.

Many people with cancer, or those at high risk for developing cancer, are:

• Unaware of the option of participating in clinical trials. Research has consistently shown that most people are not aware that clinical trials could be an option for cancer treatment or prevention.

• Unwilling to go against physician’s advice or direction. Research has shown if a person’s doctor does not recommend a trial as an option for cancer treatment or prevention, he or she is very unlikely to participate in one.

• Fearful, distrusting, or suspicious of research. For many people, the idea of being “randomized” to one treatment makes them feel they have less control over their care. Many are also fearful of being “experimented upon” and not receiving treatment for their cancer. Many people distrust those in the medical community, based on past negative experiences or the historical abuses of research participants.

• Unaware of clinical trials. The reality or the perception that there are no trials in their local community is a barrier for many people.

• Concerned about potential costs of trials. Some people who are insured fear that their insurance company won’t cover participation in a clinical trial. Those who do not have insurance may worry about costs that are not covered by the trial’s sponsor.

• Facing personal or practical obstacles. There are many costs, financial and otherwise, to participating in a clinical trial. Time and travel that are required to seek care at a distant trial site may be a concern for many people. The indirect costs of being away from work and family may also be a concern.

• Finally, some people may not wish to temporarily leave the care of their physician to participate in a trial.

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Fifteen to twenty years ago, research used to be limited primarily to white males, 30 to 40 years old. These days, virtually everyone – men, women, children, the elderly and minorities – has an opportunity to participate in clinical trials. This is largely a result of regulatory pressure from the Food and Drug Administration (FDA) to spread the benefits and burdens of research participation equitably. It has also become clear that drugs behave differently in people, depending on their gender, age and ethnic group. The National Institutes of Health – one of the government’s largest sponsors of clinical research – specifically requires that its clinical studies include women and minorities. The FDA, through regulation and regulatory guidelines, expects the same. There are, however, some specific barriers to consider for ethnically diverse populations:viNational Cancer Institute. “Cancer Clinical Trials: A Resource Guide for Outreach, Education, and Advocacy.” NIH Publication No. 02-5053.  September 2002. http://www.cancer.gov/clinicaltrials/education/out
reach-education-advocacy/ResourceGuide_Book_m.pdf  Accessed May 30, 2012.

There is long-standing fear, apprehension, and skepticism in minority populations about medical research due to real abuses that have happened in the past (e.g., the legacy of the Tuskegee syphilis study). Among these populations, there is often widespread fear and distrust of the medical care system as a result of discrimination, indifference, and disrespect. Some may feel that they do not want to give up their rights by participating in a trial, or lose their power by being “experimented upon.” Others may be skeptical about the quality of care that would be provided in a clinical trial. Some may find that trial recruitment strategies are not sensitive to their needs.

A patient care team may not mention clinical trials as an option. As noted above, many physicians do not refer their patients to clinical trials. However, some physicians may avoid suggesting a clinical trial to their minority patients, out of concern that patients would see him/her as insensitive. Moreover, some physicians may unwittingly discriminate against older patients, or those who are from certain ethnic or cultural backgrounds.

Many people may face additional problems accessing clinical trials. Depending on where they live or their access to transportation, people may have difficulty getting back and forth from a clinical trial site. Those with low income may find it difficult to take time off work or find appropriate childcare. Other barriers, such as a lack of health insurance or lack of general health care, clearly present difficulties in accessing trials.

Cultural or ethnic backgrounds may include values and beliefs that are very different from Western Medicine. Many people have cultural beliefs that Western medicine cannot address their health concerns. Different ethnic and cultural views of health and disease (e.g., fatalism, family decisions about treatment, use of traditional healers, prayer, herbal medicines, or use of complementary/alternative health practices) may make clinical trials a less attractive treatment option. For prevention trials, many may feel that the risk of a potential disease and its consequences may be less important than meeting daily needs.

Language and/or literacy barriers may make it difficult for some people to understand and consider participating in clinical trials. The complexity of forms, including informed consent documents, may also be a barrier to those considering participation in a clinical trial. Translation can also be difficult if the person translating information has not had specialized training.

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Health care professionals can provide a great service to their patients when discussing and considering participation in clinical trials. Potential candidates are encouraged to use the information they find on clinical trial sites in conjunction with information from their health care providers when evaluating the important decision to participate in medical research. The following websites provide more information about clinical trial participation and the status of pain-related studies.

• ClinicalTrials.gov is a registry and results database of federally and privately supported clinical trials conducted in the United States and around the world. ClinicalTrials.gov provides information about a trial’s purpose, who may participate, locations, and phone numbers for more details. ClinicalTrials.gov currently has more than 126,000 trials with locations in 179 countries, and lists information about more than 11,000 trials related to pain.

• CenterWatch lists more than 80,000 active clinical trials seeking study volunteers each month, involving new drugs and devices regulated by the FDA and the Department of Health and Human Services. There are currently more than 1,100 clinical trials underway for pain and pain-related conditions across the country. Listings are posted across a wide range of medical conditions and are searchable by therapeutic area, disease or geographic location.

• MedlinePlus is a web-based information service from the National Library of Medicine. Its “Health Topics” section has extensive information from NIH and other trusted sources on hundreds of diseases and conditions, including a link to clinical trials. It also includes an informative “Clinical Trials” health topic page, with material in Spanish, and an interactive tutorial on clinical trials.

• The National Heart, Lung and Blood Institute offers more information and videos about the importance of including children in clinical trials.

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