China's recent drug regulatory reform has emphasised that clinical trial data must be authentic and reliable. However, the legal consequences for breaching data integrity requirements in clinical trials remain ambiguous. On August 24 2016 the China Food and Drug Administration (CFDA) issued the draft Guideline for Handling Issues Identified in Clinical Trial Data Inspections. The draft guideline aims to clarify what constitutes data forgery and the legal consequences of non-compliance in clinical trials for different stakeholders. The CFDA is currently seeking public comments on the guideline.
On July 22 2015 the CFDA issued a circular requiring the filers of 1,622 pending drug registration applications to self-inspect their clinical trial data for compliance with the Good Clinical Practices (GCP). The circular highlighted several priority areas for self-inspection:
- the consistency of the final data for analysis with the original raw data;
- the documentation of changes;
- the compliance in the handling of samples and investigational products;
- the management of subject screening;
- inclusion and exclusion;
- keeping track of protocol deviations; and
- the reporting of adverse events.
Upon self-inspection, applicants voluntarily withdrew around 80% of their pending applications, including both domestic and international drug applications. Based on the submitted self-inspection results, since early 2016 the CFDA has initiated five rounds of onsite inspections of selected clinical trials, including some Phase I to III trials and some bioequivalence studies. Among the first three batches of completed inspections, 30 drug applications were rejected, in most instances due to the discovery of false clinical data.
To provide more guidance on the legal consequences of these CFDA-led inspections, the newly issued draft guideline addresses the following:
- The division of liability between applicants/sponsors, clinical trial institutions and sites, and clinical research organisations (CROs) – while sites and CROs shall bear liability for data integrity issues they are directly responsible for, the sponsors ultimately bear all the legal liabilities for the submitted clinical data and the drug application dossier.
- The types of GCP breach that constitute data forgery – the draft guideline gave a specific list of violations of relevant sections of GCP that constitute data forgery. Among other things, hiding certain trial data or not presenting the complete data set is considered data forgery, which can lead to a CFDA ban on future applications.
- The ban on future applications – companies that have forged clinical trial data are banned from refiling an application for the same product with the CFDA for the next three years. In particular, if data forgery is found to have occurred after November 11 2015 the CFDA will directly reject the current application under review, and the applicant will be banned from filing any applications for any drug products for one year.
- Implementing a blacklist – based on the draft guideline, blacklisting will apply not only to the sponsors, sites and CROs involved in data forgery, but also to the responsible individuals within these entities.
- The suspension of studies at study sites – if study sites are found to be involved in data forgery, or to have committed other serious GCP violations that threaten subject safety or data integrity, the sites must immediately suspend subject enrolment, rectify the violation and refrain from undertaking any new trials.
- Discretion in imposing penalties – applicants can be exempted from penalties if they voluntarily report all identified issues following self-inspection and withdraw the relevant applications. There will be leniency in penalties if applicants fully cooperate with the investigation and punctually explain and correct the identified non-compliance. Equally, applicants who decline, deter, or avoid inspections can face more stringent penalties.
Life sciences companies should arrange necessary audits of ongoing clinical trials, evaluate their level of GCP compliance and develop corrective action plans accordingly.
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