JAMIE TROIL GOLDFARB was no stranger to clinical trials from a professional standpoint, having worked for a company that recruited patients for trials. When she was diagnosed with cancer at age 30, however, the Takoma Park, Maryland, resident found herself on a road that would ultimately lead to her participation in clinical trials as a patient. Clinical trials are research studies that assign treatments to patients to test whether they’re safe and effective.
Goldfarb was diagnosed with stage II melanoma in December 2007 after a birthmark was removed from her left thigh and biopsied. In December 2009, a deep-tissue mass was discovered at the site of the mole and removed, leading to a stage III diagnosis. A sentinel lymph node biopsy and a PET scan after surgery showed no signs of disease, so there was little else to do but continue to watch for recurrence. Then, in January 2011, a PET scan revealed Goldfarb had metastases in her liver and pancreas, meaning that she had stage IV melanoma. Shortly after that, she was accepted into an adoptive cell therapy clinical trial at the National Cancer Institute (NCI) in Bethesda, Maryland. Adoptive cell therapy involves growing T cells in a laboratory and introducing them into the patient’s body to bolster the immune system. The treatment worked: By October 2013, she showed no evidence of disease, and follow-up scans since then have shown the same result.
“Without having that prior knowledge about what clinical trials were, about what they represented—especially for people with cancer—and how to access and understand them, it would have been a whole different journey, for sure,” says Goldfarb of her experiences. “People don’t know how to find clinical trials, and they also don’t know to question their doctor. If your doctor recommends a certain treatment pathway, it’s not your first inclination, if you’ve just been diagnosed with a potentially fatal illness, to question your doctor’s treatment plan right from the start. If you don’t know about clinical trials, or you know that clinical trials exist but you don’t know how to find out about them, it’s not your first instinct to question your doctor and push back on what their recommendation is.”
Less than 5 percent of adult cancer patients in the U.S. participate in clinical trials. Recent efforts to improve that number have integrated new ideas and tools into the traditional research process in order to bring patients and trials together, help patients participate in trials more easily and enable researchers to share data collected from trials more widely.
Finding Trials
Goldfarb’s experience working with clinical trials before her diagnosis meant she was well aware that taking part in a study could make a difference in the outcome of her treatment. Her son was only 11 weeks old when she received her stage IV diagnosis. “I would have been willing to travel anywhere [to take part in a trial] because it was a life or death situation,” she explains. “I needed to be sure that whatever treatment I was going to undergo, it was for the long term, so that I could be with my baby for years and years and years.”
Goldfarb took a proactive approach to researching her options and found a promising trial by seeking advice from a range of melanoma experts. A knowledgeable family friend suggested oncologists she could contact, and she learned about trials online.
Before the internet was widely used, patients typically relied on oncologists to find clinical trial information for them, says Doug Peddicord, the executive director of the Association of Clinical Research Organizations, based in Washington, D.C. Today, searchable databases that isolate key variables, such as cancer type, stage and treatment, can help patients and researchers find one another. “Now, those ‘needles’ are much more searchable within the ‘haystack,’” Peddicord says, referring to the patients who meet a particular trial’s eligibility criteria.
Researchers can find potential participants by searching huge datasets sourced from health care systems. “While you can’t necessarily identify those people exactly, you can often identify, for instance, the physician or the practice at which they’re being seen,” says Peddicord. “And you can alert the physician or the practice to the notion that they have some number of patients that meet the criteria.”
For their part, patients can look at online databases to see if any trials are a match for them. “The internet has made it easier for potential participants to learn about clinical trials,” says Rebecca Williams, the acting director of ClinicalTrials.gov, a database of private and government-funded clinical trials. “However, with more information, it also creates challenges for potential participants in understanding whether a clinical trial is appropriate for their circumstances and, if so, which types of trials would be an appropriate choice.”
An alternative to ClinicalTrials.gov is the search engine offered by the NCI, which features only NCI-funded trials and spotlights key information from the patient perspective. Eligibility criteria are prioritized over other information, and one-on-one assistance is offered via web chat, phone and email.
Advocates and advocacy groups also use the internet to share news of promising trials. Some do so via social media sites like Twitter and Facebook. These groups often have a large number of followers affected by a particular type of cancer, making it easier to ensure that people who might be eligible are aware of the trial. Other groups host their own disease-specific trial finders, like the curated search tool provided by the Fight Colorectal Cancer advocacy group. The NCI offers an open version of the framework that powers its search engine to any groups that are looking to build a searchable trials tool.
Efforts to modernize clinical trials are needed to measure treatment effectiveness in all patients.
Clinical trials could become more inclusive by making it easier for prospective participants to find out about trials they are eligible for and reducing the geographic barriers to taking part in them.
Research published in Cancer on March 18, 2014, stated that, with the possible exception of Native Americans and Alaska Natives, racial and ethnic minority groups were underrepresented in clinical trials relative to the proportion of the general population they account for.
“Having a representative population enrolled in clinical trials is essential to evaluate whether treatments are effective in all populations, or whether they might be more or less effective in certain populations,” says Grace Mishkin, a public health analyst for the National Cancer Institute’s Cancer Therapy Evaluation Program.
Participating in Trials
Goldfarb lived about eight miles from her trial site on the campus of the National Institutes of Health in Bethesda, Maryland, so she avoided some of the challenges faced by trial participants who don’t live near the trial location.
In the future, technology may be able to help cut down on travel requirements for patients who do live a long way from their trial site. For instance, an investigator could make contact with a trial participant via video call in lieu of an in-person visit. This provides the researcher with a better sense of the patient’s condition and general well-being than a phone call, while allowing the patient to remain at home. Routine data collection like blood tests could be carried out at a local medical facility, with the sample and its results being shared with the investigator either physically or digitally. Certain patient data could be collected on an ongoing basis using wearable technology—from something as simple as a step counter that measures daily physical activity to an electrocardiogram to evaluate damage to the heart caused by chemotherapy or radiation.
These methods for conducting clinical trials, sometimes referred to as “virtual” or “siteless” trials, are still taking shape as researchers learn more about what works and what doesn’t. Most current trials of this type focus on conditions that are not life-threatening, which reduces the risk of unintended consequences due to less face-to-face contact.
One issue with siteless trials that has already been identified is the challenge of providing remote oversight for participants. To address this issue, Center Point Clinical Services, a private company based in Fargo, North Dakota, that helps pharmaceutical companies carry out trials, is testing a technique that expands the role of the pharmacist. On behalf of the investigator, a pharmacist from the same geographic area as the trial participant works directly with the individual and with the participant’s regular pharmacist to monitor health and catch any unintended outcomes of the trial.
Sharing Data
In the past, data collected during clinical trials have been kept private for a variety of reasons. A pharmaceutical company might be more likely to publish clinical trial results that are positive rather than negative, or hold off on publishing successful outcomes lest they give competing companies a head start on creating a rival product. Others would prefer to avoid the risk of infringing upon patients’ privacy, rather than commit to sharing the data widely.
The Food and Drug Administration Amendments Act of 2007 introduced monetary penalties against anyone who fails to submit required clinical trial information. These rules aren’t always followed—results from the first trials subject to these penalties were due in January 2018. According to AllTrials, a project that promotes more open access to research, required information from nearly 700 trials has not yet been submitted by researchers since that deadline.
Various projects are underway to bring together the data that’s collected from clinical research. One such effort led by the nonprofit organization Vivli has developed a global data-sharing platform expressly intended to foster the reuse of clinical research data. The platform allows researchers to analyze anonymized data from different clinical trials that have already been completed.
“I think it’s a way to get as much value as you possibly can from clinical trial data,” says Vivli’s director of strategy and operations, Julie Wood. “Patients who are involved in a clinical trial are volunteering to take a risk on behalf of everyone to really drive science forward.” Wood believes there is a “moral obligation” to do as much as possible with the information collected during a trial.
Over 100 cancer studies have already been added to Vivli’s platform. Wood thinks trials that aren’t directly linked to cancer could also benefit from oncology research. Part of the appeal of having easy access to a wide range of prior research is the potential for unexpected discoveries that could occur when other work is cross-referenced, she says.
From the Food and Drug Administration’s attempts to compel investigators to share their results, to online platforms that make it easy to access this information, the groundwork is being laid to ensure that in the future, trial data isn’t hidden away.
In some cases, researchers have one eye on tomorrow even as they’re in the midst of a study. The National Clinical Trials Network (NCTN) Navigator program, launched by the NCI in April 2018, makes specimens from clinical trials dating back to the 1990s available internationally to researchers conducting studies. “In many cases, trials in the NCTN collect specimens to bank specifically so that they are available for future research that is unknown at the time of the trial,” says Grace Mishkin, a public health analyst for the NCI’s Cancer Therapy Evaluation Program. “Some research questions are developed early on, but often we don’t know what the best research would be until we have the trial results.”
It’s possible to preserve specimens long after a clinical trial has concluded and to archive huge amounts of data in digital form. Crucially, these resources can be tracked via online records so that scientists all over the world are able to use them. From the range of clinical trials available to patients to the clinical trial data available to researchers, new tools have made it possible to sift through huge amounts of information to find something that could be vitally important to a scientist’s work or to a patient’s health.
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