Paul Engstrom

Asking the right questions about a clinical trial sheds light on whether it is the most appropriate one for a particular patient and what will be expected of participants. This helps avoid surprises in the future, such as out-of-pocket treatment costs and unanticipated impacts on daily life.

Ideally, patients learn everything they need to know about a study upfront, as part of informed consent. “But as a practical matter,” says Richard Schilsky, MD, section chief of hematology/oncology at The University of Chicago Medicine, “sometimes the details don’t become obvious until after the patient chooses to participate. Then it’s, ‘Oh, my God. I didn’t know I would have to do that!’”

In fact, studies have shown that many participants don’t always understand the setup of clinical trials, the risks and benefits associated with the trial or the purpose of the trial. The National Cancer Institute and the American Society of Clinical Oncology suggest asking key questions, such as: 

 think the experimental treatment will work?

 of the trial participants receive a placebo rather than active treatment?

 scans and other procedures participants can expect to undergo? Which ones are experimental (specific to the trial) and which are part of normal care?

> What are the short- and long-term benefits

 and the short- and long-term risks of the treatment?

 if any, will the insurance provider or the participant have to pay?  

 and how often will participants have to visit it? 

It’s OK to contact the research team directly; a phone number should be listed in the clinical trial summary. Ask to speak with the trial, referral or research coordinator, or with the protocol assistant. Research coordinators, who are typically nurses, determine whether willing patients meet the study’s eligibility criteria, make sure the study protocol is followed for each patient and often serve as the link between participants and their physicians.

Articles

Questions to Ask About a Clinical Trial

After receiving a cancer diagnosis, some patients want to consider every option before deciding on treatment. Rather than waiting to enroll in a clinical trial as a last resort, they may be willing to explore the possibility upfront, seeking trials that include standard treatment in addition to the experimental approach. But identifying and ultimately participating in a study can be a challenge. Beyond learning the potential risks and benefits, patients should also understand the barriers around becoming involved.

Patients may be reluctant to participate in trials for a variety of reasons—they feel they don’t know enough, they might not meet strict eligibility requirements or they worry about how to cover the costs. Yet, as strange as it may seem, physicians are often a roadblock between patients and  trials. According to a 2010 report by the Institute of Medicine, primary care doctors might not mention cancer trials as a possibility because, as generalists, they often are unfamiliar with them&mdash;understandable, considering the National Institutes of Health track more than 122,000 clinical trials in 179 countries.

Oncologists might not mention them either—or may even discourage participation&mdash;if they object to less traditional treatments or worry about the additional time, cost and paperwork burdens they would bear on behalf of patients who enroll, a legitimate concern in this age of financially squeezed healthcare. A survey published in 2011 in the 

 found that 44 percent of 213 trial-eligible cancer patients did not recall discussing trials with their doctor.

If a patient’s oncologist doesn’t mention trials or balks at the subject, the patient should get a second opinion, says Richard Schilsky, MD, section chief of hematology/oncology at The University of Chicago Medicine, noting that an oncologist once advised one of his own family members not to become a “guinea pig.”

“Second opinions are worthwhile. Patients deserve to hear different points of view and have as much information as possible,” Schilsky says. “We know that patients have strong emotional attachments to their physicians; sometimes it’s a doctor they’ve been with for a long time. But at the end of the day, patients must do what hopefully will be best for them.”

Even if the patient’s oncologist is cooperative, finding an appropriate trial—much less one within a reasonable geographic distance&mdash;can be daunting, given every patient’s unique medical history, disease variables, demographic characteristics, eligibility criteria and the vast array of trials. David Spigel, MD, a clinical oncologist and director for the Lung Cancer Research Program at the Sarah Cannon Research Institute in Nashville, Tenn., encourages his patients to explore clinical trials databases on their own first. Later, during his free time, he digs through and narrows their findings to one or more studies he believes are most applicable&mdash;in effect, working as a translator, navigator and advocate for the patient.

“It helps me find a way to help,” Spigel says. “That makes things easier for everybody.”

[Read "Recruiting for Clinical Trials Takes Center Stage"]

Although no centralized, searchable database with up-to-the-minute information exists, the most comprehensive one is 

 from the National Institutes of Health. Others include the National Cancer Institute’s (NCI) list; 

, developed by the Coalition of Cancer Cooperative Groups; proprietary databases at drug and biotechnology companies; and the International Federation of Pharmaceutical Manufacturers & Associations Clinical Trials Portal.

Databases can be difficult to navigate, even though most provide instructions. It helps if patients know all the details of their disease and any prior treatments before searching, so they can correctly refine the search parameters. The NCI also provides live help online and by phone (800-422-6237) if patients have search-related or other questions. Patients also can try a free clinical trials matching service, like those at the 

. However, it’s important to ask other such services if they charge a fee, where they get their clinical trials information, whether they keep personal information confidential or if they represent a drug brand or pharmaceutical company.

Jim Ferrell, 59, a retired police officer in Enumclaw, Wash., says he has enjoyed “an embarrassment of riches” since he received a diagnosis of stage 4 peripheral T-cell lymphoma, a rare disease, in 2008 and participated in a trial of the drug Istodax (romidepsin). To qualify for the trial, participants had to have undergone at least one prior therapy. Ferrell had received four cycles of a chemotherapy regimen, followed by four cycles of a different regimen. When an imaging test detected four cancerous nodes two months later, Ferrell and his doctor began exploring the clinical trial option.

I haven’t had a map, yet every turn I’ve taken has been the correct one, and every door I’ve reached has been unlocked.

Ferrell says Istodax has not only been highly effective against his disease, he also didn’t encounter any obstacles along the clinical trials path and remains lymphoma-free. Ferrell strongly encourages other cancer patients to take full advantage of databases and to enroll in a suitable trial, even if it means switching to a more supportive oncologist.

“I haven’t had a map,” he says, “yet every turn I’ve taken has been the correct one, and every door I’ve reached has been unlocked.”

Finding one or more trials for which a patient may be eligible is only half the battle. To determine whether a study is appropriate and the best choice, and to avoid any unwelcome surprises down the road, patients should gather as much information as possible by talking with their doctor and contacting the research team. Although studies have shown that cancer treatment expenses within and outside of clinical trials are about the same, insurance coverage varies: Patients could end up being billed for a study-related treatment, imaging test or doctor visit that falls outside the “routine care” definition. Physicians aren’t prepared to determine what a given insurer will or will not cover, says Howard Sandler, MD, chairman of radiation oncology at Cedars-Sinai Medical Center in Los Angeles. But oftentimes, he adds, patients can successfully appeal trial-related charges. The trial consent form should distinguish between standard and investigational procedures.

Beginning in 2014, a provision in the Patient Protection and Affordable Care Act (PPACA) requires individual and group health insurance plans implemented after 2013 to cover routine costs associated with approved clinical trials. Seventeen states and the District of Columbia have existing mandates that meet the PPACA provision: Alaska, Arizona, California, Colorado, Georgia, Indiana, Iowa, Kentucky, Maine, Massachusetts, Nevada, New Jersey, Ohio, Oregon, Tennessee, Texas and Vermont. 

Of course, if a study is located out of town, there are additional expenses—for transportation, accommodations, meals and the like&mdash;that insurance won’t cover. The American Cancer Society lists many outside sources of financial aid for these and other costs. (Visit 

.) Patients might also check the Marti Nelson Cancer Foundation for a list of cancer-specific patient-advocacy groups and foundations, to see if they offer assistance. (Visit 

 and click “Cancer Resources.”) Some entities, including the Lazarex Cancer Foundation (

), earmark funds specifically for clinical trial enrollees.

There’s always an element of chance when it comes to dealing with cancer. But overcoming the hurdles associated with identifying and participating in a clinical trial depends more on determination and information-gathering than luck.

Patients often find clinical trial restrictions make it difficult to participate.

Trials & Tribulations: Pursuing a Clinical Trial Requires Determination and Education

A warning for newly diagnosed cancer patients eager to explore their treatment options online: Snake oil salesmen are still very much alive—and thriving.

Coffee enemas, special diets based on hair analysis, bioresonance therapy (electromagnetic waves used to diagnose and destroy a variety of diseases, including cancer), supplements derived from zeolite (a mineral that occurs naturally in volcanic rock and ash) and nutritional products, such as “cancer teas”—can all be found on the Internet. These and other so-called therapies beckon to cancer patients who, perhaps frantic for help and too easily swayed by false promises, may be tempted to forego professional advice and mainstream treatment, with possibly disastrous consequences.

Add to this quackery all of the misinformation, testimonials that don’t reflect the bigger picture, bias,conspiracy theories about standard cancer care, and conspiracy theories about standard cancer care, and uncertainty as to which legitimate therapies apply to whom exactly, and the online hunt for truth and clarity may seem like chasing a mirage.

[Learn how to judge the cancer information you find online]

“Even on reliable websites, statistics and medical information can be confusing and shocking,” say Susannah L. Rose, PhD, and Richard T. Hara, PhD, in their book 

100 Questions & Answers About Caring for Family or Friends With Cancer

. “Filter all information through your doctor to get the real story, clarify concerns and get the answers to all questions regarding treatment.”

The good news: There are tried-and-true criteria to help you gauge the reliability of Web content up front so you can bypass the fool’s gold and focus instead on the valuable nuggets. Developed by the National Cancer Institute, U.S. National Library of Medicine, Federal Trade Commission and other trustworthy sources, these criteria dig beneath the surface to establish, among other things, the sponsorship, origin, quality and currency of online information. In addition, a few authoritative websites debunk some specific products, claims, myths and hoaxes related to cancer, providing a fact-check service of sorts to dispel lingering doubts.

[Credible cancer websites to help fact-check what you find online]

Results from a 2005 survey illustrate why an ability to winnow out dubious content is so essential in the digital age. Nearly 50 percent of about 5,600 respondents in the Health Information National Trends Survey said the Internet was their most recent source of information about cancer, compared with nearly 24 percent who cited a healthcare provider as that source.

Yet healthcare providers are a key factor in this equation. A problem for many cancer patients, beyond the reliability of online information, is figuring out which research findings apply to their particular circumstances, says Paul Helft, MD, a gastrointestinal oncologist at the Indiana University Melvin and Bren Simon Cancer Center and director of the Charles Warren Fairbanks Center for Medical Ethics in Indianapolis. The challenge is greater for patients with rare cancer, because there are fewer studies and uniform treatments to read about.

Helft says that even if their online searches are productive, most of his patients still want something the Internet can’t offer: expert advice. “They don’t come in and say, ‘I think I’ve made up my mind what I’m going to do.’ They come in and say, ‘I have a better idea, a better understanding of what I’m supposed to do, but I want you to tell me what you think I should do.’”

Carol Haines is a big believer in such advice. In July 2011, Haines, a 38-year-old healthcare project manager in Pittsburgh, received a diagnosis of colon cancer. She had a tumor removed and underwent chemotherapy and radiation. The oncologist’s treatment plan guided her Internet searches so she could focus on the best, most reliable information and avoid the questionable content she encountered, such as pitches by drug companies, websites abroad, sites seeking donations and sites pushing herbal remedies and other alternative treatments.

In Haines’ view, a lot of testimonials in blogs and discussion groups about chemotherapy and radiation side effects are negatively skewed, perhaps because patients whose experiences were more positive have moved on with their lives and are too busy to post. “When I started reading about treatment,” she says, “I thought I would have to give up all my activities, to not work and just basically sit at home for the next six months. It turned out not to be that way at all.”

Most troubling for some professionals is the blatant quackery, online versions of which are more rampant than ever, largely unregulated and virtually unstoppable. Herbal remedies touted as cancer therapies are particularly disconcerting for Barrie Cassileth, PhD, because many consumers don’t realize that these may interfere with chemotherapy and prescription medications.

“In fact, herbal remedies can be very dangerous, especially if someone is on medication of any kind because there are a lot of herb-drug interactions,” says Cassileth, founder and chief of the Integrative Medicine Service at Memorial Sloan-Kettering Cancer Center in New York City. Empirical evidence in the cancer center’s “

” database casts welcome light on more than 250 substances, techniques and products that allegedly cure cancer.

Still uncertain about that “miracle cure” you saw online? Many times, a simple test suffices: If it sounds too good to be true, it probably is.

Tips on finding credible cancer information on the Internet.

Finding Reliable Cancer Information Online

Mention “bank rescue” these days and most people cringe. But there’s another type of repository—human tissue banks for cancer research&mdash;that also need help and pose important implications if they can’t keep pace with scientific advances.

Studying stored tissues that have been offered for research by patients can provide answers to some of the most common questions asked by people who have cancer, such as, “Will this cancer come back?” and “How long do I have to live now that I have cancer?” and “What is the best drug to use in treating my cancer?”

New ideas and therapeutic strategies need to be validated, and often, that validation process depends on tissue and biorepository banks. Notable examples of successful efforts include the development of tests to determine a woman’s risk of recurrence after breast cancer surgery, the development of several new drugs that target specific cancer-causing genes and the ability to determine the chance of a patient’s tumor responding to a given therapy based on testing the tumor. 

The biobanking field, despite some progress in recent years, is still playing catch-up with genomic and proteomic studies in the lab. Armed with powerful, cutting-edge techniques in this age of “personalized medicine,” researchers can analyze the genes and proteins in banked specimens for biomarkers that may signal the development of cancer in individual cells, offer clues about response to treatment and lead to new cancer tests or therapies. However, proper statistical analyses require large numbers of cases.

The challenges for biobanking are daunting. A partial list includes inconsistent collection, processing and storage of tissue, which can alter its molecular composition and skew experimental outcomes; shortages of high-quality tissue; outdated preservation techniques; the high cost of and inadequate funding for repositories; patients’ lack of awareness about tissue donation; and, for competitive and other reasons, institutions’ hoarding specimens they might otherwise share with researchers elsewhere.

“The way we’re doing things is just inadequate—maybe worse than inadequate,” says Carolyn Compton, MD, PhD, director of the Office of Biorepositories and Biospecimen Research at the National Cancer Institute (NCI) in Bethesda, Md. 

Collectively, biobanks store tissue, such as tumor slices, blood, saliva, urine, DNA and other bodily materials in formalin-fixed, paraffin-embedded blocks or at very cold temperatures, or sometimes using both methods along with the related clinical, pathologic or molecular information. By law, medical facilities must retain tissue samples for a specified number of years (the number varies among states), which could prove useful if patients later seek a second opinion, their cancer recurs or a new genetic test becomes available. 

Separate from that process, fully informed patients may also consent to donate some of their leftover cancerous tissue—stripped of identifying information&mdash;for research at no cost to them, with the understanding that they will probably never personally benefit or even learn if scientists actually use it. However, the tissue needs to be linked to clinical information about the patient, such as the pathology of the tumor and long-term outcome&mdash;including if and when the tumor recurred or the patient died of the disease. Research questions related to that data could be asked years from now when new analytic technology develops.

Part of the difficulty in bringing more rhyme and reason to the biobanking industry is its scattershot nature, aside from the fact that there’s no oversight by any federal regulatory agencies. Biobanks vary widely. They may be public or commercial enterprises. They are spread out among universities and cancer centers, as well as different types and sizes of hospitals, pathology labs, drug companies and other facilities, sometimes in multiple places within a single institution. They might focus only on a certain type of cancer, as does a bank founded in 2005 by the Multiple Myeloma Research Consortium at a cost of between $2 million and $3 million. And they range from a small freezer tucked in the back corner of a lab to a multimillion-dollar operation with state-of-the-art equipment. Consider this: More than 300 million biospecimens are stored in public and private repositories throughout the U.S.

It’s a scenario that can send researchers hunting for just the right specimens. “Hodge-podge milieu” is how Deborah Collyar in Danville, Calif., describes it.

Collyar, 53, who is president of PAIR: Patient Advocates In Research, a group that helps get results to patients more quickly, twice received diagnoses of breast cancer, in 1990 and 1995, and underwent surgery, chemotherapy and radiation. After the second recurrence, she decided to donate tissue blocks from both of her cancers to research, retrieving and carrying them herself from the Bay Area hospitals where she had received treatment to a breast cancer biorepository at the University of California, San Francisco. She had learned enough about cancer research by that point to understand the specimens’ potential value.

“I actually had to make that happen myself,” Collyar says. “Most people are not going to do that or know how to do that. I really didn’t know how either. I just kept asking questions.”

Michael Morse, MD, a clinician and associate professor of medicine at Duke Cancer Institute in Durham, N.C., who is studying vaccines that stimulate the immune system to attack cancer and who relies on dendritic cell specimens for his research, says patients rarely bring up the topic of tissue donation. When he broaches the subject, “most people are perfectly fine with that because they are not going to need another procedure done for it,” he says. “They also like the idea of helping future research.”

Although the gap between biobanking and advances in the lab may not be closing as quickly as some would like, there have been positive developments. For example, a fairly standard practice now in cancer-related clinical trials is to collect, store and study tissue from the participants, then maintain the specimens for future investigations by those researchers or by scientists elsewhere who demonstrate a need for them. Not having to gather and store tissue anew saves resources.

A recently completed study involving approximately 10,000 patients with newly diagnosed, early-stage estrogen- and progesterone-positive, node-negative breast cancer took that approach. The TAILORx (Trial Assigning IndividuaLized Options for Treatment [Rx]) study used the Oncotype DX Breast Cancer Assay to determine which participants would be more likely to benefit from chemotherapy, thus reducing such treatment in women who were not likely to benefit from it. The primary results will be available in 2015.

Those banked specimens “will allow us to address other clinically important questions—study other tests, other biomarkers&mdash;without having to repeat the entire trial,” says principal investigator Joseph Sparano, MD, an oncologist and professor at Albert Einstein College of Medicine and Einstein Cancer Center in New York.

Encouraging signs of progress at the national level include efforts to establish a central, public-private cancer tissue repository called the Cancer Human Bank (caHUB) and research on new ways to preserve tissue. The NCI offers best practices on the operational, technical, ethical, legal and other issues in biobanking while a research group has published guidelines to foster more thorough, accurate and standardized reporting in medical journals of how biospecimens have been handled so researchers are aware of circumstances that may negatively impact their own follow-up study results.

Original plans for the NCI-funded caHUB called for collection and storage of many high-quality tissue specimens and distribution to researchers beginning in 2015. However, the federal funding crunch has nixed that plan, at least for now. Instead, the NCI’s Office of Biorepositories and Biospecimen Research, where caHUB is based, will use $23.5 million in federal stimulus funds to expand research on standards for collecting, processing, storing and disseminating tissue specimens, says Jim Vaught, PhD, the office’s deputy director. 

“We still think the original caHUB central repository concept is very valuable and plan to come back to it if possible,” he says.

Could advances in the science of tissue preservation also help narrow the distance between cancer labs’ rapid headway at the microscopic level and biobanks’ tissue quality problems? Allison Hubel, PhD, associate professor of mechanical engineering and a cryopreservation expert at the University of Minnesota’s Masonic Cancer Center in Minneapolis, thinks so. She and her colleagues are developing microfluidic devices that can remove preservation solutions from cells without causing molecular damage, which reduces quality. In addition, they are investigating synthesized as well as naturally occurring compounds that might work better than current, less-than-ideal preservatives.

As Hubel notes, researchers depend on the generosity of today’s cancer patients for tissues that may yield dividends sometime in the future. The big question is whether biobanks can do their full part to help make those payoffs a reality.

Consider this: More than 300 million biospecimens are stored in public and private respositories throughout the U.S.

To benefit research, tissue repositories must be accountable.

Paul Engstrom

Questions to Ask About a Clinical Trial

Trials & Tribulations: Pursuing a Clinical Trial Requires Determination and Education

Finding Reliable Cancer Information Online

Why Banks Need Your Tissue for Research

Latest News