China's Center for Drug Evaluation has released a long-term proposal document outlining plans to improve the regulation and management of clinical trial data, acknowledging the lack of unified rules and variable standards. The release follows revelations that fraud and misconduct at China-based clinical trials led to the nine-month delay of US approval for Bristol-Myers Squibb (US)'s Eliquis (apixaban) last year.
IHS Global Insight perspective | |
Significance | China's Center for Drug Evaluation (CDE) has released a proposal paper outlining ambitious medium-to-long-term goals for improving the management of clinical trial data in China. |
Implications | The proposals include drawing up unified rules on data management, setting up an accessible registry of trials, and building a database. |
Outlook | The move follows recent damaging revelations of misconduct and fraud during trials held in China by Bristol-Myers Squibb (US), and separately by GlaxoSmithKline (UK). |
China's Centre for Drug Evaluation (CDE), part of the China Food and Drug Administration (CFDA), has released a "Proposal to Standardise Pharmaceutical Clinical Trial Data Management".
The report seeks to provide a medium-to-long term blueprint that will address a number of issues in management of clinical trials in China, including poor standards in clinical trial data supervision that are unevenly applied, with insufficient supervisory powers, and lack of a comprehensive guidance, leading to low-quality clinical trial data. These problems are now viewed as urgently requiring attention, described as contributing to China's clinical trial bottleneck, limiting the ability to objectively assess drugs' safety and efficacy, at the same time hindering the country's drive towards greater innovation and international competitiveness.
Concrete targets outlined in the report include establishing working groups, led by the CDE's deputy director of biostatistics, Huang Qin, to drive ahead on the following six specific targets, with scheduled completion dates also established:
- Technical specifications on data management: Following a study of guiding principles applied in foreign countries and consultation with stakeholders, draw up guidance by end-2013.
- Clinical trial registry: Set up a platform for the registration of clinical trials, with such information to be made publicly available – to be established by August/September 2014.
- Unified data standards: Study and promote unified data standards according to principles of the international non-government advisory group the Clinical Data Interchange Standard Consortium (CDISC) – a special working group to draw up proposals and seek views from stakeholders from now through to 2014.
- Data submission format requirements: Draw up proposals and gather feedback from July 2014.
- Data quality evaluation: Research into data evaluation methods to be carried out during 2013–14.
- Clinical data database: Prototype database to be set up during 2015.
For a link to the CDE's proposal (in Chinese), see here.
Outlook and implications
China has become a global hub for clinical trials over the last five to 10 years, with growth driven by such factors as the requirement for all imported drugs to undergo local clinical testing, and increasing investment by the government into promoting innovation under the 12th Five-Year Plan. Multinational firms are increasingly including the country in global trials and establishing standalone research and development (R&D) operations, with the huge, treatment-naïve patient population contributing to the average cost of a Phase I trial being as low as 15% of the cost of holding the trial in a developed market (source: Excel Pharmastudies).
Regulation has not kept pace with the growth, however, and lack of manpower at the CDE means that just gaining approval to conduct a trial can take around 12 months, in a process burdened by red tape and requirements not seen in other markets (see China: 11 March 2013: CDE 2012 annual report shows slow progress in improving China's drug registration process). More worrisome are revelations of misconduct during China-based trials that have come to light in recent weeks: fraud and poor management at trials run by Bristol-Myers Squibb (US) and contract research organisation (CRO) PPD (US) led to a nine-month approval delay for anticoagulant Eliquis (apixaban), while GlaxoSmithKline (UK) last month dismissed the head of its China R&D centre following manipulation of clinical data in a published paper (see China: 9 July 2013: US FDA reveals misconduct at Chinese-held trial delayed Pfizer/BMS's Eliquis approval and China: 12 June 2013: GSK dismisses head of China R&D centre after probe into research article data).
The CDE's proposals will therefore be broadly welcomed by the industry, particularly multinational companies operating in China. Under China's current opaque rules, clinical data requirements can vary depending on the type of drug application being filed, and on negotiations between drug firms and the CDE – domestic applications can be favoured with eased requirements in terms of endpoints or patient numbers in comparison with imported drugs, for example. More stringency in terms of the management of clinical data could therefore entail a more level, predictable playing field. CROs will also be paying close attention to developments, with Chinese CROs operating to different standards than international CROs in the country. Furthermore, Chinese government funding for the biopharmaceutical sector has seen a number of Chinese firms turning away from generic drugs towards biosimilars and bio-betters, and improved regulation, as well as more CDE manpower with biologics expertise, is viewed as essential by industry watchers. The CDE's proposal refers to the need to specifically develop biologics data requirements, and the fact that the project is headed up by the deputy director of the biostatistics division is significant. The proposal paper should be seen as providing guidance to the industry as to what direction reforms and development will take in this area over the coming years, with significantly greater levels of funding required for the under-resourced CDE; whether this materialises remains to be seen.
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