In a time when we need agile and open research regulation, the “FDA’s own documents reveal agency’s lax, slow, and secretive oversight of clinical research,” according to an October 1 article from Science. One case is that of osteopath Michael Harris, who was cited by the FDA for almost ten years for “egregious errors” in trials he oversaw. His firm Aspen Clinical Research out of Orem, Utah, had contracts “to evaluate many drugs, including ones aiming to treat postoperative pain, pediatric schizophrenia, and migraines.” Citations included informed-consent violations, medical assessments by nonqualified staff, and failure to report abnormal test results. Further, he effectively hid subjects’ use of opioids, SSRIs, and antipsychotics, skewing results and raising safety concerns. Aspen’s, “records were disorganized, contradictory, and sometimes backdated in a way that ‘begs the question of the authenticity and veracity of data collected.” All together, the errors might be scientific misconduct, fraud, and substantial violations of the rights of human study subjects.
FDA inspectors had informed Harris he, “could be subject to fines, permanent disqualification from clinical research in the United States, and legal prosecution.” But the problems continued, as found by inspections in 2014, 2015, and 2019. Each time, Harris admitted some allegations, strongly denied others, and “promised to improve.” Throughout this process, FDA never officially sanctioned the doctor or sought any penalty. And FDA did not make the allegations public, tell subjects that they may have been at risk, or inform sponsoring firms “that their data might have been compromised.” All the while, pharma and device companies went on contracting with Aspen, which has been paid millions of dollars for “at least” 65 clinical trials since 2011. At present, they are “recruiting people for nine new trials on Alzheimer’s disease, autism, depression, and other serious disorders.” Harris had no comment to Science, “and the agency refused to discuss its dealings with him.” The doctor’s business partner Wayne Croft calls FDA’s handling of Aspen, “bureaucratic harassment that drove away business,” and he asserts that the agency gave Dr. Harris “post-traumatic stress.”
Review of 11 Years of Data Shows Problems Common
A look at FDA’s trial oversight over the last 11 years hints that the case of Aspen and doctor Harris are, “commonplace.” Enforcement, “is often light-handed, slow-moving, and secretive.” Science looked at 1600 FDA “inspection and enforcement documents for other trials that FDA said violated rules and law, almost all acquired by FOIA requests. The materials showed that, “Clear corrections of inspector-reported dangerous or unlawful clinical trial practices were the exception, even amid signs that trial participants were harmed and that data underpinning evidence-based medicine were corrupted.” In the rare cases when FDA officially warned scientists that they broke the law, FDA, “often neglected to ensure that fixes occurred.” And many cases were closed, “on the basis of unverified claims by those accused.”
“Warning letters” from FDA over serious trial transgressions are also becoming more rare; e.g. they issued 99 in Obama’s first 3 years in office versus 12 in Trump’s first years. “It certainly looks like FDA is enforcing clinical trial requirements much less frequently, which is troubling for protecting subjects’ welfare and ensuring the validity of data for our medical products,” indicated Patricia Zettler, an attorney worked for FDA from 2009 to 2013, and who “reviewed Science’s findings.” FDA had a $5.7 billion budget for 2019, and among its tasks, “is overseeing most clinical research in the United States and some conducted elsewhere for the U.S. market—including many high-stakes vaccine and drug trials for COVID-19.” It has 102 inspectors for complaint response, site visits, and records review of trial sites. During the period looked at by Science, the agency did about 6,700 inspections of researchers or the institutional review boards that do immediate trial oversite.
Range of Responses Available for Violations
Inspections can result in “no action” declarations, “official action indicated” (OAI) reports that require violators to “clean up” their violations, warning letters that threaten further action unless, “corrections are made promptly.” Further, FDA has the authority to disqualify scientists from conducting research. Despite having the resources to enforce laws and regulations, FDA has wielded this power, “less and less frequently since the beginning of the Obama administration. Under President Donald Trump, the number of enforcement actions has plummeted.” Science found that FDA nearly always rules that there is no action warranted or else asks for voluntary correction. Holly Fernandez Lynch, attorney and University of Pennsylvania bioethicist, opines that FDA “prefers” voluntary action. “When people fail to comply, it’s hard to know what to do about it, short of completely ending a trial or all research at that institution,” which could deprive patients an effective treatment in trials, Lynch said.
Science’s findings included one case in which a researcher resolved an action by “pledging” to refrain from further research. And when he violated the pledge, there was no visible response from FDA. The agency defended itself in an email, stating that its, “strategy [is] to focus inspectional resources on higher-risk facilities.” And they assert that they try to deal with clinical trial issues early on, so “an issue that might warrant a warning letter could be resolved before the problem rises to that level.” And the relative secrecy of FDA’s processes means that trial subjects are unaware of possible harm, which violated a “basic human right,” according to Vinay Prasad, hematologist-oncologist at UC San Francisco who looks are how, “drug funding affects research.” Science goes on to document other cases in which it looks like FDA failed to take corrective actions, failed to follow up, and generally “dropped the ball” when it came to doing its job.