Britain Adopts More Stringent Rules for Phase I Trials of High-Risk Compounds

After a disastrous phase I clinical trial last year that left six volunteers seriously injured, Britain’s Medicines and Healthcare Research Agency (MHRA) has tightened its clinical trial regulations. Now studies of certain classes of drugs that have never before been tested in humans will have to follow new guidelines on a range of topics, including dosing protocols and training for investigators. “Everyone realized that the fi rst priority is the safety and well-being of subjects,” said Gordon Duff, M.D., Ph.D., professor of molecular medicine at the University of Sheffi eld. “So most stakeholders were pulling in the same direction.” Duff led the expert scientifi c group (ESG) — an independent body of 19 people commissioned by the U.K.’s Secretary of State to investigate details of the TGN1412 trial and to recommend changes to existing procedures. The group consulted various stakeholders — both national, such as the British BioIndustry Association and the Association of the British Pharmaceutical Industry, and international — before drafting their fi nal report, which was published in December. The report concluded that none of the parties involved in the TGN1412 trial violated current clinical trial regulations. However, it did recommend revamping existing procedures for certain compounds to better protect clinical trial volunteers. It singled out specifi c classes of “highrisk” drugs that regulators should scrutinize more closely: biological molecules with novel mechanisms in man, new agents that are highly species specifi c, and new drugs directed toward immune system targets. ESG’s recommended changes span both clinical trial sponsors and regulatory agencies and cover fi ve specifi c areas: preclinical research, drug dosing strategy, reviewing clinical trial applications for risky compounds, facilities for fi rst-in-man clinical trials, and training for clinical investigators. While some critics have argued that tighter regulations in Europe might drive clinical trial sponsors to other countries, others see little reason for concern. “Most of the recommendations aren’t dramatic changes,” said Richard Ley, spokesperson for the Association of the British Pharmaceutical Industry. “Pro cedures should be reviewed and revised every few years anyway.” The MHRA has already implemented many of the ESG’s recommendations, spokesperson Stephen Hallworth said. Prompted by the report, the European Medicines Agency has issued similar guidelines for E.U. member countries regarding fi rst-in-man studies to better harmonize regulations across the continent.