The US Food and Drug Administration plans to tighten up reporting requirements for sponsors that observe or suspect data falsification in the course of a clinical trial.

The agency is working on a proposed rule as part of a newly announced Human Subject Protection and Bioresearch Monitoring (HSP/BIMO) Initiative, which centres largely on data quality and oversight of institutional review boards (IRBs).

The rule will clarify sponsors’ obligations so that the FDA can intervene earlier in cases where investigators or other parties have tampered with clinical data, explained Dr Janet Woodcock, deputy commissioner for operations and chair of the HSP/BIMO steering committee. She declined to give a timetable for the proposed rule, which has been in the pipeline for a number of years.

A previous version was withdrawn from the FDA’s regulatory agenda in spring 2002. However, a proposed rule on reporting data falsification was back on the table when the agency launched a review of its existing Bioresearch Monitoring Initiative in December 2004.

The HSP/BIMO Initiative, which was unveiled at last week’s annual meeting of the Drug Information Association, will inevitably draw accusations of window-dressing, particularly as a number of the projects mentioned are already completed or in hand.

Moreover, the announcement comes as congressional pressure builds over allegations that the FDA glossed over evidence of fraud when it approved Sanofi-Aventis’ antibiotic Ketek (telithromycin) in April 2004. Dr Woodcock insisted, though, that the DIA presentation had been planned “for a long time” and marked the point at which the HSP/BIMO initiative was moving “into high gear” after months of introspection and internal process analysis.

Dr Woodcock did concede that around half of the initiative was about improving data quality, which had relevance to the Ketek – as did the shift towards a more risk-based, real-time approach to inspecting sponsors, investigators, IRBs or contract research organisations (CROs).

The problem with reporting data falsification, she told PharmaTimes, was that the existing regulations were ‘ambiguous’. If a sponsor had submitted information to the FDA that turned out to be fraudulent, the sponsor was legally obliged to tell the agency. But that did not always happen when the data were ‘out there’, even though the FDA was aware of ‘serial offenders’ involved in multiple clinical trials, Dr Woodcock said.

The growth of clinical trials into large, decentralised operations spanning multiple sites and sometimes multiple countries was a key driver for the HSP/BIMO initiative, along with the increased participation of vulnerable trial subjects and a shift towards electronic record-keeping. One outcome of decentralisation has been the proliferation of sub-contractors in the clinical trial process, not all if which can be “reached” effectively under the current regulations, Dr Woodcock pointed out.

Decentralisation has also hampered the FDA’s existing bioresearch monitoring programme, which has been spread across a number of agency centres with only a small central staff. The goal now is a more unified programme with ‘different governance structures’. The FDA also wants to move towards automation and standardisation of the whole clinical trial process.

The HSP/BIMO Initiative is a ‘cross-cutting’ programme that embraces human drugs, biological products, devices, foods and veterinary medicine. It falls under the umbrella of the FDA’s Critical Path initiative, which aims to modernise and streamline medical product development.

Besides tougher reporting rules for clinical fraud, current HSP/BIMO projects include guidance on adverse event reporting to IRBs and finalising a rule on foreign clinical studies not conducted under an investigational new drug application.

Among the completed projects are guidance for industry on using a centralised IRB process in multicentre trials (published March 2006); and information sheet guidances for IRBs, clinical investigators and trial sponsors (five published in January 2006).