China Outlines Ambitious Roadmap To Clean Up Clinical Data Quality

China Outlines Ambitious Roadmap To Clean Up Clinical Data Quality
PharmAsia News
July 10, 2013

Executive Summary

Reeling from a series of scandals involving clinical trial data, China FDA has put forth a comprehensive plan to tackle the issue, stressing urgency and the need to meet global standards. While many challenges remain, the agency says it will work closely with industry stakeholders to strengthen the “quality mentality.”

The Center for Drug Evaluation at China FDA has laid out six goals to improve clinical trials data management, focusing on registration, collection, submission, handling, reviewing and warehousing of data. The objective is to raise the quality of Chinese clinical trials data to international standards.

The immediate goal is to implement a process-based regulation with “dynamic supervision” over clinical trials conducted in China. “The release is intended to allow industry to gain a better understanding of the regulator’s overall thinking and progress so far,” said CDE in a report released July 9.

Clinical data quality issues have risen to a level where they must be addressed right away, the agency acknowledged. In a blunt assessment to start the report, CDE said: “The current clinical data management level is poor, and varies from facility to facility. There is a lack of regulatory supervision, and relevant technical guidelines.”

“The poor quality in clinical data has become a bottleneck, severely deterring the ability to objectively assess drug efficacy and safety,” the report states. “It also harms our country’s new drug innovation and competitiveness in international markets.”

The report follows a series of scandals involving clinical trial and research data in China that have impacted multinational players. In one example, it was recently revealed that U.S. FDA delayed approval of Bristol-Myers Squibb Co./Pfizer Inc.’s blood thinner Eliquis (apixaban) after learning of misconduct at a clinical trial site in Shanghai, where some patients received the wrong drug and trial records were altered.

Vowing to quickly bring China’s clinical data quality up to international standards, CDE divided its work plan into six topics, and outlined details, implementation methods and timelines for each one. Under the plan, CDE will:

1. Establish and release clinical data regulations;

2. Set up a clinical trial registry;

3. Promote uniform data standards;

4. Establish data submission requirements and format templates;

5. Review data quality; and

6. Set up a clinical data warehouse.

Implementation will be led by a team of CDE leadership and Deputy Director of Biostatistics Huang Xin. Group members include division heads and reviewers of chemical drugs and traditional Chinese medicines, human resources and IT personnel.

For each goal, there will be a leadership team, comprised of CDE staff and experts, and a research team comprised of academic experts, industry representatives and contract research organizations (See: Implementation Plan for Regulating Clinical Data Management – Chinese language ).

Big Variations Let Down Quality

Among the six goals, the most lacking is uniform data standards, said Lily Zhao, director of biometrics at local CRO TigerMed Consulting Ltd.

“Up to now, there is no review over the data submitted, so the data come in all shapes and shades,” Zhao told PharmAsia News. “The huge variation has greatly impacted data quality.” Zhao sits on the CDE research team for data standards, which held its initial meeting in June.

Except for the clinical trial registry, the other five topics are interlinked, Zhao pointed out. Being upstream, regulations and standardized data requirements will lead to uniform submissions and formats, and then to easier review and eventual establishment of the data warehouse.

CDE has set 2014 as the time to release a draft guideline on standardized data requirements. The agency will establish a special taskforce under the China Coordinating Committee (C3C) for the Clinical Data Interchange Standard Consortium (CDISC), and hold regular meetings to draft and complete the guideline.

Although the process sounds straightforward, the challenge is daunting, Zhao cautioned. Only a few domestic CROs and drug developers know about CDISC, although it has been used widely in developed countries for years. (CDISC is a global non-profit organization that establishes standards to support the acquisition, exchange, submission and archive of clinical research data and metadata.)

Recalling the first taskforce meeting, where Zhao and other multinational attendees explained CDISC to participating physicians, Zhao expects that more clinical trial stakeholders will need to get involved, and that much time and effort will be required.

Many physicians, site directors and CROs in China will need to familiarize themselves with CDISC for the first time, Zhao said. In addition, biometrics talent is lacking among local CROs and drug makers, she explained.

Nevertheless, CFDA has taken the first step, and the taskforce is moving to accelerate the learning process. According to Zhao, the team has proposed starting from a pilot study, which would employ CDISC concepts to redesign the study, mapping out relevant issues and solutions. Zhao hopes the hands-on experience will help local firms grasp the concepts quickly.

Issues Remain

Despite the ambitious plan and quick start, expectations should be held in check due to several issues, industry experts caution.

One issue is the language barrier. All CDISC documents are written in English, and translation into Chinese will take time, noted Zhao. Although translation of core concepts has been completed, terminologies are still waiting to be converted.

In addition, adopting CDISC concepts to situations on the ground in China will be a challenge. Local players must first accept the new concepts. Currently, a large gap exists in clinical data quality among local CROs with some taking shortcuts to complete tasks faster, Zhao said.

What’s lacking in CFDA’s clinical data roadmap is increased penalties for violators to help ensure compliance, she said. In terms of faking study data or altering study results, the penalties have not been steep enough to deter bad actors, Zhao said.

In China, A Revised Relationship

Unlike in many countries, where principal investigators serve as working partners with study sponsors, Chinese physicians often behave more like authority figures, which could complicate efforts to improve data quality and integrity, experts say.

“They [Chinese doctors] are always so busy. Because there are so few fulltime clinical study physicians and nurses, physicians usually delegate clinical studies to residency physicians and simply sign it [without reviewing],” noted Zhao.

CROs will have to assume a larger role, including reviewing and uncovering variations in data. “It’s very important for a CRO to stop and halt wrongdoings in a timely manner. And correct them when they occur,” she said.

Nurturing good relationships with Chinese physicians is vital, Zhao said. Without a rapport, miscommunication can occur, or worse, delay corrective actions.

It’s no wonder, therefore, that a spate of violence targeting Chinese physicians has some companies worried about the potential impact on clinical trials.

The situation, however, is slowly improving with the emergence of clinical study coordinators (CRCs). A good CRC can help reduce physician burden, and keeps a study running smoothly and on track.

Despite the challenges China’s CDE believes that clinical data quality must be dealt with now.

“We will follow the goals and progress outlined in the plan, and tirelessly push for more standardized clinical data management. It’s our hope that other stakeholders work with us closely to strengthen the quality mentality,” the report states.

Zhao shares CDE’s urgency. “If we don’t do it now, it will get harder to correct it later,” she said.