National Cancer Institute
U.S. National Institutes of Health | www.cancer.gov

NCI Home
Cancer Topics
Clinical Trials
Cancer Statistics
Research & Funding
News
About NCI
Cancer Clinical Trials: The In-Depth Program



Preface






Introduction






The Clinical Trial Process






Clinical Trial Design & Interpretation of Results






Advancing Cancer Care Through Clinical Trials






Participant Protection in Clinical Trials






Barriers to Clinical Trial Participation






Conducting, Referring to, and Locating






Case Study






Glossary






Bibliography



Page Options
Print This Page
Print This Document
View Entire Document
E-Mail This Document
View/Print PDF
Quick Links
Director's Corner

Dictionary of Cancer Terms

NCI Drug Dictionary

Funding Opportunities

NCI Publications

Advisory Boards and Groups

Science Serving People

Español
NCI Highlights
Virtual and Standard Colonoscopy Both Accurate

Denosumab May Help Prevent Bone Loss

Past Highlights
7. Case Study

The Clinical Case
Finding a Clinical Trial
Sample Points to Discuss with the Patient Considering a Clinical Trial
Conclusion

The Clinical Case

Mr. Joe Smith, a 59-year-old African American male, presents to his primary care physician, Dr. Bob Brown, in rural Wisconsin. He has been complaining of difficulty with initiating urination and frequency. He presents clinically with an abnormal rectal exam and an elevated prostate-specific antigen (PSA) of 8 ng/ml (normal in a 59-year-old Black male is less than 4 ng/ml). Mr. Smith's mass is biopsied and the results reveal a prostatic tumor. The nearest comprehensive cancer center is 100 miles away, and Mr. Smith wants to be treated by Dr. Brown. He says he wants to stay close to his home and family, and does not want to be cared for by "those big city doctors."

Mr. Smith decides to undergo a radical prostatectomy at his community hospital. Surgery reveals a 1.5 cm tumor with clear margins, negative pelvic node involvement, and unilateral seminal vesicle involvement, which puts Mr. Smith at high risk for eventual tumor spread. To complete his clinical staging, a bone scan and CT scan are completed. Mr. Smith's tumor is formally staged. At his 3-month followup visit, post-operatively, his PSA is 0.2 (undetectable).

Dr. Brown closely follows Mr. Smith. Three years after his surgery his PSA has slowly risen to 11, but his bone scan and CT scans remain negative. Dr. Brown informs Mr. Smith that there are many clinical trials for men with prostate cancer at all stages. He explains that these trials are being conducted to try to find the best methods for cancer prevention, early detection, and treatment. At this point in his disease, Mr. Smith does not wish to consider a clinical trial, so he continues to receive standard care. Dr. Brown recommends starting standard treatment with hormone therapy injections monthly. The patient's PSA drops to less than 0.2 again.

Two years later, the PSA begins to rise to 15 and a bone scan now shows abnormal uptake in multiple ribs and the thoracic spine. Mr. Smith is started on an anti-androgen drug and his PSA drops to 10 at his 3-month followup visit. One year later his PSA has risen to 40, and he now says he has mild rib pain. Dr. Brown explains to Mr. Smith that he needs to consult with an oncologist from the cancer center, Dr. Mary Jones, and that Mr. Smith may need to see her. Mr. Smith somewhat reluctantly agrees to see Dr. Jones. Dr. Jones recommends exploring available clinical trials because Mr. Smith is young, is in good health with mild symptoms, and has a tumor that now appears to be progressing.

Finding a Clinical Trial

How can Dr. Brown or Dr. Jones find an appropriate clinical trial for Mr. Smith?

Dr. Jones decides to check NCI's PDQ system, because her center has no active trials for prostate cancer. The PDQ system will allow her to see current active clinical trials and their eligibility criteria. (More information on PDQ.)

Dr. Jones uses the NCI PDQ system to assess what, if any, clinical trials are available for Mr. Smith. Using the Internet, she accesses the site as follows:

  • Enters the clinical trials section of Cancer.gov

  • Selects "Finding Clinical Trials"

  • Selects PDQ Search Form

  • Enters the relevant data; hits search (appropriate studies will be retrieved)

  • Reviews the trials

If a physician does not have Internet access, how can he or she find a trial?

Clinical trial information is always available through NCI's Cancer Information Service (CIS) at 1-800-4-CANCER (1-800-422-6237).

After reviewing available trials, Dr. Jones selects a phase 2 trial entitled: A Phase II Randomized Study of High-Dose Ketoconazole With or Without Alendronate Sodium in Patients With Androgen Independent Metastatic Adenocarcinoma of the Prostate (2001) to discuss with Dr. Brown and Mr. Smith.

Mr. Smith is clinically eligible for the study. Participants are randomized to one of two arms: 1) a single oral dose of ketoconazole on day 1, and then 3 times daily oral dose beginning on day 8, versus 2) a single oral dose of alendronate sodium on day 1 and a single oral dose of ketoconazole on day 3 and then daily alendronate sodium and 3 times daily ketoconazole beginning on day 8. Participants who experience a clinically complete remission (CR) receive treatment for an additional 60 days beyond CR. Mr. Smith would have to be willing to have followup visits at NIH in Bethesda, MD, every 2 months and be seen in the NIH Cancer Center every 2 weeks for evaluation of toxicity and drug tolerance.

Sample Points to Discuss with the Patient Considering a Clinical Trial: Randomization, Patient Protection/Myths, and Insurance

Randomization

As a health care professional it is often challenging to discuss the concept of randomization with patients. Patients can feel threatened knowing that neither they, nor their doctor, can choose what treatment they will get if they enter a randomized trial. They may feel that the arm of the study that is standard care or closest to standard care, is the best option. People may also be concerned that if they enter a randomized clinical trial they will not receive treatment; they may receive just a "sugar pill." How can they be sure?

Dr. Jones began her discussion of randomization with Mr. Smith, his wife, and their two grown sons by explaining that this study has an objective group of professionals who monitor the study called a data and safety monitoring board (DMSB). The DMSB evaluates the data from the clinical trial to interpret if the therapy or technique being studied appears to be better (more beneficial) or worse (more harmful) than standard therapy. A trial can be halted early to allow all participants access to a clearly more beneficial intervention, or to protect participants from harm.

Dr. Jones explained that there are three phases for clinical trials and that randomization is generally seen in phase 3 studies where researchers are unsure whether a new intervention is better than the currently accepted standard therapy for a specific cancer type. She discussed how patients entering a phase 3 trial (and, as in this case, some phase 2 trials) are randomly assigned to groups (called randomization) and that neither the patients nor their doctors choose which therapy or technique they will receive. This is done because if physicians determined which therapy participants would receive, there could be an unconscious bias in their assignments. They could tend to assign patients with a more hopeful prognosis to the experimental therapy group and make the new therapy seem more effective than it really is. Similarly, if patients were allowed to choose which therapy they would receive, the results could also be influenced. Patients with a less hopeful prognosis could tend to pick the experimental treatment, for example, which may lead that treatment to look less effective than it really is.

Myths

Mr. Smith and his family have many questions regarding what they have heard and read about clinical trials. How would you answer these questions?

1. How do I know I am really safe if I enter this trial? You and I both know there are bad feelings in our community about research.

Fact: Tragedies have occurred in the past related to clinical trials. The African American community most notably remembers the infamous Tuskegee syphilis study, which followed, but did not treat, African American men with syphilis. There are now strong safeguards in place to protect research participants from the notorious human rights abuses of the past which include:
  • Government oversight and regulations

  • Institutional review board (IRB) review and approval of a clinical trial before it begins and annually while it is in progress

  • An informed consent process which gives potential participants the information they need to decide about participation, including foreseeable risks and benefits

  • Data and safety monitoring boards which ensure minimization of risks, integrity of trial data, and oversight to end a trial early if clear benefit or harm arises from the intervention being studied (usually used in phase 3 studies)

2. Aren't these clinical trials only for dying cancer patients?

Fact: Clinical trials are not just for patients with the most advanced disease. In fact, many newly diagnosed cancer patients participate in clinical trials. If only the sickest patients participated in treatment trials, researchers would not know how to treat patients with earlier stages of cancer. Phase 3 treatment includes all stages of cancer, from the most advanced to the most localized. These trials enroll hundreds or thousands of patients. Phase 1 and 2 cancer clinical trials, which enroll fewer than 100 patients, seek people with few treatment options or people who have exhausted all the current treatment options, which is Mr. Smith's case.

3. Aren't people who join clinical trials just "guinea pigs" for research?

Fact: People who decide to take part in a clinical trial are called participants, and strict guidelines are in place to ensure that these volunteers are treated as such:
  • A participant has the right to withdraw from a trial at any time. The participant's decision does not jeopardize his or her future treatment and he or she may discuss further treatment options with the study physician or be referred back to a primary care provider for standard care.

  • Although people fear that trial participants are treated like guinea pigs, reports from actual trial participants disagree. According to a Harris Poll conducted in 2000, the vast majority of trial participants said their overall experience was positive. Ninety-seven percent said they were treated with dignity and respect and that the quality of care they received was "excellent" or "good." More than 80 percent said they did not receive more tests than they felt were necessary and 86 percent said their treatment was covered by insurance.

4. Mr. Smith's wife is very concerned that cancer patients who join clinical treatment trials get a sugar pill (placebo) instead of really being treated. Will my husband really get treatment?

Fact: In phase 3 cancer treatment trials, participants with cancer get either a new treatment or the best standard treatment. In phase 2 trials, like the one Mr. Smith is considering, different schedules and combinations of two drugs are being evaluated for their effectiveness. It is unethical to deprive any person with a serious illness or condition of the best available treatment. There would be no placebo involved in Mr. Smith's treatment.

5. His oldest son is wondering if only people who have cancer can participate in a clinical trial. Aren't my brother and I at higher risk now?

Fact: Treatment and diagnostic trials are designed for people who already have cancer; however, genetics, prevention, and screening trials are designed for persons at risk of developing cancer. This is relevant for Mr. Smith's sons who now have an increased risk for prostate cancer. Dr. Jones suggests that the sons make an appointment to discuss a cancer prevention clinical trial.

Insurance

Dr. Brown is wondering whether participating in this cancer clinical trial will cost Mr. Smith more than standard treatment. Will insurance cover the costs?

The costs of new treatments for different cancers vary. Some treatments under study cost no more than standard therapies. Others, such as bone marrow transplants, are very expensive. There are hundreds of insurance companies and managed care organizations in the United States and each has a different policy about covering clinical trial costs. In general, most companies have contract language that prohibits coverage for "experimental therapies." However, decisions are often made on a case-by-case basis, and costs for patient care in clinical trials are often covered.

The best way to evaluate each situation is to ask questions such as the following:

  • What will the total patient care costs be?

  • What parts of the treatment, if any, does the study provide free of charge?

  • What parts of treatment must be paid for by the participant or the participant's insurer?

  • What is the situation for people who have no health insurance?

  • Will total patient charges be higher for a clinical trial

    than for standard care?

  • How often have insurers reimbursed all costs of the new therapy?

  • Are there other resources or organizations that might help cover the fees or provide services, such as free transportation?

Another option is to discuss reimbursement issues with the insurance company ahead of time. The company is unlikely to promise coverage before the fact, but it may give information about general policies and trends. In considering costs of out-of-town treatment or follow-up care, patients should remember to include travel-related costs. The research team conducting the study will know how many times participants will need to visit, for how long, whether housing or stipends will be provided, and whether participants will be hospitalized during their stay.

Conclusion

After meeting with Dr. Jones and discussing their concerns, the Smith family met with Dr. Brown to discuss his view of the trial. Mr. Smith decided to enter the trial. After four months and his second evaluation, his PSA has decreased to 14 ng/ml, and he has no bone pain. He will continue for another cycle of therapy and be reevaluated in 2 months. After his initial apprehension eased and treatment began, Mr. Smith was able to verbalize satisfaction in both his decision to enter the trial and in the level of care and attention he received.

Back to Top

< Previous Section  |  Next Section >


A Service of the National Cancer Institute
Department of Health and Human Services National Institutes of Health USA.gov