Clinical News Roundup: Scientists Hate NIH Definition of Clinical Trials

By Ed Miseta, Chief Editor, Clinical Leader

Science magazine reports some scientists hate the U.S. National Institutes of Health (NIH’s) new definition of a clinical trial. Nancy Kanwisher is one example. Kanwisher is a cognitive neuroscientist who often performs studies on college students, such as asking them to lie in an MRI machine and view a photo while she records their brain activity. Although the studies do not test a treatment, NIH could soon consider her work to be a clinical trial.

If that happens, the designation could impose a host of new requirements on studies that have already passed an ethics review. Those requirements could include following different standards for funding applications and reporting results on clinicaltrials.gov.

NIH officials say they simply want to ensure that all clinical trials—including those testing drugs, medical devices, and behavioral interventions—meet recently bolstered standards for rigor and transparency. But Kanwisher and others say that the agency’s widening definition of clinical trials could sweep up a broad array of basic science studies, resulting in wasted resources and public confusion.

Kanwisher believes a massive amount of dysfunction and paperwork will result from the decision, and could hobble basic research. To prevent that outcome, she and dozens of other researchers, along with several scientific societies, have flooded NIH with letters and emails expressing concern about the policy. The policy was announced in September 2016 but is now being implemented.

ClinicalTrials.gov Registration May Be Misleading

Companies are registering stem cell therapies on the ClinicalTrials.gov website but asking patients to pay for unapproved care, according to an analysis published in Regenerative Medicine.  The author says the companies are using a trusted government resource as a marketing tool.

Earlier this year an article in the New England Journal of Medicine article described three patients with age-related macular degeneration who lost vision after bilateral intravitreal injection of autologous adipose tissue-derived stem cells at a Florida clinic.  Two of the women came to the clinic after reading a description at ClinicalTrials.gov.

Registering a therapy on clinicaltrials.gov is possible because criteria are not terribly rigorous, according to the author of the new perspectives article. A listing must indicate whether there is an institutional review board, a "yes" or "no" response to indicate whether the treatment is U.S. Food and Drug Administration (FDA) regulated, and, if so, the investigational new drug (IND) or investigational device exemption (IDE) number. An observational study need not have an IND or an IDE.

Leigh Turner, PhD, associate professor at the Center for Bioethics at the University of Minnesota, Minneapolis, searched ClinicalTrials.gov for the terms "patient-sponsored," "patient-funded," and "self-funded." Turner found seven clinical trials, each enrolling more than 100 individuals. He identified 11 other registered clinical trials using a database of companies that provide direct-to-consumer stem cell–based treatments. One trial (listed by Cell Surgical Network) had an estimated enrollment of 3000.

Companies can use a ClinicalTrials.gov listing to attract non–science savvy, and often desperate, patients, Dr Turner says. He points to a news release from StemGenex, for example, that claims, "By providing access to registered clinical studies through the NIH, we are providing patients with the ability to choose a stem cell treatment center with the highest standard of care."

Dr Turner notes several harms of enrolling in an unregulated stem cell clinical trial, including the absence of adequate preclinical data to support use in medicine; likely use of an open-label, uncontrolled trial design, which is unlikely to provide useful research data; and request for payment, which can amplify a placebo effect. Moreover, the FDA must approve asking participants to pay for investigational or unapproved treatments, which it generally doesn't do.

Insurance Approval Rates For Trials Rose Under ACA

Approval rates for privately insured patients seeking to enroll in oncology clinical trials increased after the passage of the Affordable Care Act. This according to a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research. The study was conducted by David S. Hong, MD, deputy chair and associate professor in the Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston; and Kenneth L. Kehl, MD, a member of MD Anderson's Division of Cancer Medicine.

Previous studies explained that since 2000, publicly funded Medicare has covered the routine costs of clinical trial participation. Patients who were covered by private insurance often faced a patchwork of coverage options, with different insurers and different states determining whether participation in a clinical trial would be covered.

In 2010, the passage of the Patient Protection and Affordable Care Act (ACA) mandated that private insurers cover "standard of care" costs of clinical trial participation, effective Jan. 1, 2014. Hong, who oversees Phase 1 clinical trials at MD Anderson, said that after the ACA mandate took effect, he perceived that patients in his practice were experiencing fewer delays in being approved for clinical trials, and undertook the study to see whether his observation was true on a larger scale.

Hong and colleagues analyzed 2,404 referrals from the departmental database of the Clinical Center for Targeted Therapy at MD Anderson, comparing rates of insurance clearance and the time to clearance in three separate time periods: July 2012-June 2013; July 2013-December 2013; and January 2014-June 2015.

FDA Continues Push For More Hispanics In Trials

Hispanics comprise 17 percent of the population, yet make up only 8 percent of participants in clinical trials. That means Hispanics have less access to experimental cutting-edge treatments. It also means researchers have less data on how a drug works in that population, which is a problem since studies have shown different ethnic groups might respond differently to treatments.

“Studies should represent the demographics of the country,” said Dr. Jonca Bull, an assistant commissioner on minority health at the Food and Drug Administration. “We need to close that gap so we can better understand how a particular drug or therapy works in different communities.”

There are many reasons why Latinos do not enroll in these studies, including lack of information, disparities in access to health care, and not being fluent in English. Dr. Otis Brawley, chief medical officer with the American Cancer Society (ACS), said Latino families are open to participating in clinical trials, especially to help treat a sick son or daughter, but they need advice from a doctor to navigate the process.

Federal officials aim to augment these numbers. In March, the FDA launched a campaign to educate Hispanics about medical studies. As of July 5, there were 94,545 ongoing clinical trials in the United States, according to the NIH’s official website, clinicaltrials.gov. The primary physician usually helps a patient find a medical study, although the advent of the internet in recent decades has meant a growing number of patients discover trials themselves online.

Korean Clinical Trials Increase In 2017

Clinical trials carried out by South Korean pharmaceutical companies inched up in the first half of this year, while overall biomedical research and test numbers declined globally. According to the findings by the Korea National Enterprise for Clinical Trials, experiments and tests carried out locally made up 2.19 percent of the global total for the January-June period, compared with 2.08 percent a year earlier.

Meanwhile, the number of global clinical tests decreased 22.5 percent during the same period, mainly due to more than a 40 percent drop in tests by U.S. pharmaceutical firms.

"The global clinical trial industry is becoming more difficult to forecast due to changes in new drug developments and paradigm changes," said Ji Dong-yun, a KoNECT official, noting that local companies are keeping their competitiveness despite the changes.

Industry officials attributed the increase to robust research and development spending by local players in recent years. Four major South Korean pharmaceutical companies -- Hanmi Pharmaceutical Co., Green Cross Corp., Daewoong Pharma and Chong Kun Dang Pharmaceutical Corp. -- spent more than 100 billion won ($86.9 million) each on R&D for the first time in 2016. The latest move marks a significant change from 2014, when Hanmi Pharmaceutical was the only player that allocated more than 100 billion won to R&D.