Clinical News Roundup: Should You Be Concerned About For-Profit Review Boards?

By Ed Miseta, Chief Editor, Clinical Leader

STATnews is reporting that when it comes to clinical trials, for-profit review boards are taking over hospitals. But should they be doing so, and should you be concerned?

Arthur Caplan heads the division of bioethics at Ney York University Medical Center and sits on the board of WIRB-Copernicus Group, the largest commercial institutional review board (IRB) in the country. For years he warned medical researchers about the risks of paying businesses to evaluate their clinical trials. He felt for-profit review boards were in it for the money, and were less concerned about protecting patients. But he now believes the shift to commercial IRBs is over, and the days of hospital or academic review boards are not coming back. Many drug companies now encourage researchers to use commercial boards, which are considered more efficient than non-profit boards.

In June 2016, the National Institutes of Health (NIH) announced that US-funded trials carried out at multiple research centers must begin using a single IRB, with few exemptions. Since few universities or hospitals have the capacity to review study protocols and track adverse events for far-flung institutions, the rule is expected to be a windfall for commercial IRBs.

But there is also a downside to using them. The FDA reports that between 2008 and 2014 there were twice as many violations and problems with commercial IRBs as with their non-profit counterparts. One review board was even disqualified by the agency after repeatedly failing FDA inspections.

Although federal regulators at the FDA and the Department of Health and Human Service’s Office for Human Research Protections are charged with overseeing review boards, they don’t have sufficient staff to monitor the thousands of IRBs and tens of thousands of studies conducted in the U.S. and overseas.

NIH-Funded Center to Study Inefficiencies in Clinical Trials

Researchers at the Duke Clinical Research Institute (DCRI) and Vanderbilt University Medical Center (VUMC) have received a federal grant to study how multisite clinical trials can be conducted more rapidly and efficiently. DukeTODAY notes the seven-year, $26.5 million grant for a joint Trial Innovation Center (TIC) is supported by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The center will be a key component of the Trial Innovation Network, which is the newest part of the Clinical and Translational Science Award (CTSA) Program.

Danny Benjamin, faculty associate director of the DCRI, and Gordon Bernard, director of the Vanderbilt Institute for Clinical and Translational Research (VICTR), are the grant’s principal investigators. “The DCRI and Vanderbilt partnership is a perfect fit for the TIC,” said Benjamin. “The academic research organization model at the DCRI and Vanderbilt’s informatics and central institutional review board model are poised to immediately contribute to the NIH’s vision of high-functioning networks for clinical research.”

The Trial Innovation Network will include other TICs, as well as Recruitment Innovation Centers (RICs), which will study ways to engage more volunteers in clinical research. Both programs will leverage the expertise and resources of the NCATS CTSA Program.

5 Smarter Approaches To Oncology Trial Design

Drug Discovery & Development reports oncology trials fail far too frequently, and often for similar reasons. In looking at the reasons these studies fail, five prevalent issues emerged: assumptions that undermined a trial’s design; inadequate patient selection criteria; problematic phase 2 trials; over-interpretation of subgroup analyses; and optimistic selection of a non-inferiority margin.

The following approaches are recommended to avoid these issues:

To minimize the risk of optimistic assumptions undermining a study’s design, an adaptive design strategy can be deployed; for instance, include a  sample size re-estimation (SSR). By deploying an SSR promising zone approach, a study’s initial optimistic design assumptions can be adjusted as data accumulates.

Early development must address biomarkers and how to characterize relevant patient populations. If questions remain about which populations to enroll, an adaptive enrichment design can identify relevant predictive markers during a Phase 2 study.

Regarding problematic Phase 2 trials, studies need to be designed to evaluate efficacy and toxicity outcomes correctly and simultaneously. Independent central imaging is recommended in Phase 2 studies, particularly if primary endpoints include PFS or time to progression (TTP). Finally, when making a “go/no-go” decision to move to Phase 3, it is prudent to assume the true therapeutic effect in the targeted patient population is smaller than the observed Phase 2 result.

While regulatory guidelines discuss the planning and presentation of subgroup analyses, developers often still over-interpret results. To minimize the false discovery rate, one strategy is to conduct each subgroup comparison at a low significance level. Any findings based on subgroups should also be supported by a clinical rationale.

It is often not straightforward to clearly define the success criteria of non-inferiority studies. Selection of non-inferiority margin should use clinical judgment of acceptable efficacy loss or the treatment difference between the standard therapy and placebo. For example, FDA draft guidance suggested that margins can be selected to show that a fraction of the benefit of a standard therapy is preserved, often 50 percent of the active control effect.

UPS Expands Clinical Trial Logistics

UPS has announced a significant global expansion of its healthcare-specific capabilities to support clinical trials. UPS’s investments in a range of specialized solutions will help pharmaceutical companies and clinical investigators move sensitive materials and specimens globally, particularly in and out of complex geographies.

Building on its expansive, integrated network, UPS has made advancements specifically targeted to meet strict clinical trial logistics requirements. Enhancements include: the healthcare compliant development of an easy-to-use shipping system for clinical investigator sites; an expansion of the healthcare control tower network, package intercept and re-icing capabilities; and upgraded operations to move temperature-sensitive biological specimens in and out of more than 60 countries more efficiently. Making these investments, together with utilizing an established network of local specialty couriers, helps UPS serve the clinical trial research community by providing efficiency in the transport of specimens without sacrificing service.

“Improved health outcomes through sophisticated drugs and vaccines starts with successful clinical trials,” said Geoff Light, UPS vice president of global healthcare strategy. “Optimized logistics is an integral component of medical research and development, and our goal is to help clinical investigators reach any part of the world with maximum efficiency. We will continue to invest in the right global solutions with the aim of becoming the preeminent leader in biological specimen transportation.”

Is Better Integration Needed Between ClinicalTrials.gov and Drugs@FDA?

An article on OncologyNurseAdvisor notes analysis shows better integration is needed between ClinicalTrials.gov and Drugs@FDA. Although Drugs@FDA may be useful for validating trial primary outcomes found on ClinicalTrials.gov, it was far less useful for validating secondary outcomes and information about adverse events, including deaths. This finding is based on an analysis of data from 100 trials available on both websites.

The comparison was funded by the National Library of Medicine and led by Lisa Schwartz, PhD, and Steven Woloshin, PhD, from The Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire.

All primary outcome measures posted on ClinicalTrials.gov were matched with publically available data from Drugs@FDA in the study sample and were found to be largely consistent. In contrast, only approximately half (51 percent) of the secondary outcomes listed on ClinicalTrials.gov were identified at Drugs@FDA. Serious adverse events and deaths also could not be validated for most trials because Drugs@FDA typically only reports such data aggregated across trials.

The researchers concluded that better integration between the two sites is needed. Even if all the numbers reported in ClincalTrials.gov were completely accurate, information on the trial design, conduct, or analysis would be incomplete and could affect conclusions about the trial results assessed in Drugs@FDA.