ACT accelerates clinical trials

Asian Clinical Trials (ACT) is a clinical research organisation which has cut down clinical trial report time from months to a few weeks, says Akhtar Pasha

Prior to Oracle Clinical implementation we have executed three projects [involving data management] in two years. Post-implementation [Oracle Clinical] we have done three projects in four months, says Venkatraman Sunder

Pharmaceutical companies spend 37 percent of their R&D budgets on speeding up clinical trials. A large part (30 percent) is outsourced to Clinical Research Organisations (CROs). Getting a new drug to market can cost as much as $500 million and take up to 15 years. Nearly half that time is spent on clinical trials. A big part of the problem is that clinical-trial information is often scattered through numerous systems, making it difficult for clinicians to get a complete view of the data. CROs are looking at solutions that help automate the clinical trial process of testing and reporting on the safety and effectiveness of new drug targets. This is an area that is ripe for e-business applications.

Asian Clinical Trials (ACT) a Hyderabad-based Clinical Research Organisation popularly known as ACT has a large complement of experienced and well qualified research professionals representing a wide range of therapeutic areas and research functions. ACT has successfully conducted or collaborated, on significant research trials, with pharmaceutical and biotechnology sponsors and major CROs of the USA, UK, and India.

Slow going

A CRO such as ACT has thousands of data items from the clinical trials of a single project. Data from more than 95 percent of the thousands of clinical trials conducted annually are captured using pen and paper, which often results in costly mistakes. One of the key challenges for ACT was to manage and automate thousands of clinical trial processes of testing and reporting on safety administered by the US Food & Drug Administration (FDA). As per FDA regulations a computer generated, time-stamped audit trail of operator entries and actions that create, modify and delete records has to be maintained. Secondly, US pharmaceutical customers want their CROs to use a system, which is in compliance with 21 CRF Part II as laid down by the FDA.

ACT did two trials before finalising on Oracle Clinical. In one such trial Venkatraman Sunder, vice president & head – Clinical Data Management, ACT recalls, “It was a vaccine trail involving 202 patients consisting of a 60 page report on each, 12,120 pages of clinical data in all. The process involved capturing data (from various test reports over a period of time), cleaning, analysing and validating the data and then entering it into the legacy application developed by us about a year and half ago. Even though we completed this successfully, we had to face challenges which took a long time to resolve. It took us two months to design the database and an additional four months—to enter the data (single data entry), manually verify the entries, generate queries, get queries resolved from the sites and complete the report. After closing the trial, it took 60 to 70 days to finish data entry operations and close the study.” In all one project used to take eight months to execute.

Eliminating errors

Error handling is an absolute must in any clinical trial. The legacy system used by ACT did not have some key features to eliminate or catch errors during the data entry process. ACT had to manually take printouts and cross check with CRF pages. After the validation of software, query resolutions (mistakes or errors and certain queries which were in the CRF pages) had to be generated manually in Word. Data was then exported to an Excel sheet that was not secure. “Since we are not software pros to fully validate the software developed by us in Oracle, we had to answer many questions from the sponsor,” says Sunder.

Automate it

With Oracle Clinical 4.5.0.0 the above challenges are taken care of automatically. Mistakes are automatically tracked with double data entry. Oracle Clinical is fully validated software from Oracle and well tested. Every time a particular query needs to be generated onsite in the hospital where the clinical trial is being conducted, one can generate the same within Oracle Clinical and send it to the investigators. “This automatically creates a log of activities within Oracle Clinical. On getting a response from the investigators, we close the query resolution file within Oracle Clinical after updating the data,” says Sunder. Oracle Clinical has multiple levels of security, which ensures that a data entry person cannot change the data; a person resolving queries cannot view data for which he does not have authorisation. A reviewer need not change the data and also create a complete log of activities right from the beginning of the study till the job is completed as logging is automatic.

Double data entry ensures that mistakes committed by two data entry operators for pages from the same CRF forms are resolved automatically and the final data is 99.5 percent accurate.

Two different persons independently use the same data entry forms to key in data. During the second round, any mismatch between the first and second rounds results in a screen popping up notifying the operator of the error. Most mistakes are rectified during the second round.

Why Oracle Clinical?

During the evaluation process that was conducted in December 2003, ACT looked into ‘Clintrial’, a solution from Phase Forward which is widely used in the US and Australia as well as several other clinical trial solutions from different vendors before zeroing in on Oracle Clinical. There were two distinct advantages of using Oracle Clinical over other packages. Sunder says, “Local support is very crucial for our kind of business. It should be available 24 hours a day when the project is live. We cannot afford to delay delivery as it will cost millions for our customers. Not many vendors have local support available in India and in many cases people have to come from outside India for resolving problems. Then there were problems with integrating a database with the application. Oracle Clinical comes with a database.”

Smooth rollout

In mid-February 2004 ACT raised a purchase order for Oracle Clinical. Infosys was engaged for implementing it [Oracle Clinical 4.5.0.3 Version] and the company trained ten people from ACT on Oracle Clinical and the process was completed in early March 2004. ACT went live with Oracle Clinical on 12th March 2004.

Slashing durations

A dermatology project undertaken post-implementation of 6800 CRF pages (680 patients with 10 pages per patient) got executed in 18 days flat. The time taken for building the fully validated database using Oracle Clinical took about nine days and the double data entry process took another nine working days. Sunder says, “Most significantly, Oracle Clinical has helped us in cutting down the time for development of eCRF, in entering the data, validating the data and closing operations. The result is that we can do the same job ten times faster.”

Multiple levels of security ensure zero errors

In ACT’s earlier data management operations there was no security mechanism and data was manually exported from the database to an Excel file. After implementing Oracle Clinical, the CRFs were built using Oracle Clinical at the time that the database was built and all security levels were set up. The software takes care of setting the security levels. The event log is generated by Oracle Clinical and the audit trail helps verify system integrity.

Easy validation

Setting up validation using Oracle clinical is a breeze. For example, if ACT is setting up the validation for haemoglobin levels and as per the protocol only patients within the range of 8.5 to 14.5 are to be considered for the study; ACT sets up the question in Oracle Clinical to accept data in this range only. In case, an investigator who is doing the trial has indicated in the case report form for a particular patient that the haemoglobin level is 7.5, that forms a protocol violation. In such event, at the time of data entry, the mistakes committed by the investigator will be known through the query that is generated automatically by Oracle Clinical, as the data is not within the specified range. “These queries are sent to the investigator to confirm that the haemoglobin was 7.5 as entered by him and if so, we need to remove this patient from final analysis as we were not supposed to enrol any patient who is falling outside the haemoglobin range of 8.5 to 14.5. These types of validations are very easy to set-up in Oracle Clinical”, says Sunder.

Query management

Query management in Oracle Clinical is simple and it generates a log of events for all queries sent to the investigator and till it is fully resolved, the system will not allow the study to be closed and data to be extracted for statistical analysis. Query resolution through Oracle Clinical helps ACT to raise reports to investigators. The query management tool eliminates manual intervention. Sunder says, “Prior to the Oracle Clinical implementation we have executed three projects [involving data management] in two years. Post implementation [Oracle Clinical] we have done three projects in four months. This is the Return-on-Investment (RoI).”

akhtar@expresscomputeronline.com