Clinical News Roundup: Is 80 Percent Of China's Clinical Data Fabricated?

By Ed Miseta, Chief Editor, Clinical Leader

Radio Free Asia (RFA) is reporting that a government investigation in China has revealed fraudulent practice on a massive scale in clinical trials. China's food and drug regulator recently carried out a one-year review of clinical trials, concluding that more than 80 percent of clinical data is "fabricated," state media reported.

The scandal is the result of "breach of duty by supervision departments and malpractice by pharmaceutical companies, intermediary agents and medical staff," the State Food and Drug Administration (SFDA) said in its report. The review looked at data from 1,622 clinical trial programs of new pharmaceutical drugs awaiting regulatory approval for mass production, according to an expose in the Economic Information Daily newspaper.

More than 80 percent of applications for mass production of new drugs have been canceled in the light of the findings, with officials warning that further evidence malpractice could still emerge in the scandal. According to the SFDA report, much of the data gathered during clinical trials were incomplete, failed to meet analysis requirements or were untraceable, the paper cited a source in the agency as saying. It said some companies were suspected of deliberately hiding or deleting records of adverse effects, and tampering with data that did not meet expectations.

However, RFA notes the scandal should came as no surprise to industry insiders. "Clinical data fabrication was an open secret even before the inspection," the paper quoted an unnamed hospital chief as saying. It said China's generic drug industry is plagued with quality problems, hence the need for the manipulation of clinical trials data to meet standards that are high on paper.

Many "new" drugs are simply combinations of existing drugs, while clinical trial outcomes are written beforehand, with the data massaged to fit in with it, the report said. It singled out third party inspection agencies known as contract research organizations, saying they have become "accomplices in data fabrication due to cutthroat competition and economic motivation."

Healthcare professional Luo Liang told RFA that the domestic pharmaceutical industry struggles to turn a profit under current conditions. "The domestic market for Western pharmaceuticals in China is either confined to very straightforward generic products that have been around for a long time ... or revolves around joint-venture pharmaceutical manufacture with foreign companies," Luo said. "Either that, or Chinese pharmaceutical factories get hold of the formula for certain drugs whose patents have expired. There are no new drugs in development in the same way that there are overseas."

Biotech Firms Leverage Patient Advocacy

The Boston Globe is reporting early-stage biotech companies are honing a new tool in their drug development efforts: patient advocacy. In order to raise awareness of diseases and trials, and to encourage patients to discuss their disease with regulators, startups are tapping patients and patient groups.

“No one can doubt the power of the patient,” says Annie Ganot, the mother of a 6-year-old boy with Duchenne muscular dystrophy and head of patient advocacy at Solid Biosciences LLC. “The science should not be dictated by patients, but the patients’ voice should be heard.”

At a panel hosted by the Massachusetts Biotechnology Council, Ganot and other speakers cited the recent successful campaign to persuade the FDA to green-light Exondys 51, a Duchenne drug developed by Cambridge’s Sarepta Therapeutics Inc. Hundreds of patients and their families — including representatives of patient organizations that funded Sarepta’s clinical study — packed an FDA advisory committee meeting in April to offer emotional testimony in favor of the drug. The advisers and some FDA staffers contended the therapy had not been proved effective, but the agency overruled them and approved it. Whether the Sarepta case will be a blueprint for other companies working on rare disease medicines remains to be seen.

EMA Contests Trial Transparency Decisions

The European Medicines Agency (EMA) announced it has appealed two interim orders by the President of the General Court of the EU, which suspended the release of clinical study documents requested by third parties under a new transparency regulation. The first order blocked the release of a study report for PTC Therapeutics’ Translarna (ataluren), a Duchenne’s muscular dystrophy treatment, until a final ruling is provided. EMA says it was planning to provide access to the study report in response to an access to documents request, with appropriate redactions in accordance with the regulation.

The second order, issued at the same time, blocked the release of three toxicity studies for Intervet’s Bravecto (fluralaner), a veterinary medicine used to treat flea and tick infestations in dogs and cats. PTC Therapeutics and Intervet both filed the cases to stop EMA from granting access to the non-clinical and clinical information (including clinical study reports), arguing that the release of the requested documents would infringe their right to protect commercially confidential information contained in their dossiers.

“Our approach to transparency has been welcomed by many of our stakeholders and these court cases are a good opportunity to test our rules on making available to the general public the documents on which EMA’s scientific opinions on medicines are based,” said Stefano Marino, EMA’s Head of Legal Department. “Our position that clinical reports are not confidential per se was confirmed by the adoption of the recent Regulation on clinical trials. They may contain some residual commercially confidential information which should be redacted. However, a sort of ‘blanket’ protection from disclosure for documents supporting an authorization for a medicine seems neither consistent with the legislation nor advocated by our stakeholders, including an overwhelming majority of pharmaceutical companies. We will welcome a clear indication on this point from the Court of Justice.”

New Assessment Hopes To Improve Clinical Research

The National Board of Medical Examiners (NBME), one of the nation’s leading assessors of health professionals, hopes to improve the quality of clinical research by introducing the Certification of Excellence in Clinical Research (CECR).

With several major cases in the news about clinical trials gone awry, the new NBME exam will evaluate a clinical researcher’s knowledge, with a goal of helping to protect the well-being of trial participants, reducing delays and mistakes, and helping identify areas for improvement.

The four-hour and fifteen-minute written exam uses realistic scenarios to assess a clinical researcher’s foundational knowledge in areas such as study design, ethics and data management. In addition to a numerical score, each test-taker will receive diagnostic information about his or her performance, enabling them to help identify the need for additional training or experience.

The exam was developed with expertise from veteran members of the clinical research field, including representatives from industry, academic research organizations, contract research organizations, training and education programs, grant-funding agencies, hospital systems and institutional review boards.

Despite Hype, Gene Therapy Drugs Are Not Close To Approval

Most experts in the medical field will tell you that gene therapy has finally come of age, but the numbers tell a different story. MIT Technology Review reports that despite 30 years of research and a bigger pipeline than ever, only a small number of gene therapy trials have completed late-stage testing or are currently in late-stage trials.

The concept of gene therapy—replacing or adding a gene to correct a faulty, disease-causing one—was first tested in a clinical trial in 1990. That ushered in a period of enormous hype, with news headlines proclaiming a life-saving approach. Then, in 1999, came the first patient death from an experimental gene therapy. That had a chilling effect, quelling much of the initial excitement.

The chill has thawed, and today hundreds of clinical trials testing gene therapies are ongoing or recruiting. Early data from recent trials have shown incredible promise for gene therapies targeting certain inherited diseases: patients have seemingly been cured of hemophilia and rare types of inherited blindness.

But the majority of such gene therapies are in phase I trials and probably won’t reach patients for many years. According to clinicaltrials.gov, only five late-stage gene therapy trials—that is, phase 3 or 4—are actively open or recruiting patients, and another five late-stage trials have been completed.