Clinical trials become tech-savvy

The clinical trials industry is going through an exciting phase and IT is at the heart of this revolution. Arshiya Khan finds out how

Dr Ajoy Kumar, Chief Executive Officer, Neeman Medical International.

The Indian pharmaceutical industry has recently witnessed a phenomenal rise in the number of clinical trials being conducted within the country. The availability of a huge drug, naive patient population and trained medical professionals, coupled with the latest technological infrastructure, has made India a favourable destination for conducting global clinical trials. According to Centerwatch, the Indian clinical trials market has grown from $35 million in 2002 to $120 million in 2006. The market is estimated to be worth $250-300 million by 2010. As a consequence, data volumes generated from these trials has also risen.

The success of the Indian IT industry and the resultant BPO boom has instilled confidence amongst clinical research organisations (CROs) and pharma companies to venture into clinical data management outsourcing. "Some CROs like Neeman have created clinical data management infrastructure besides other services as a full fledged service provider, including site management, monitoring and pharmacy," says Dr Ajoy Kumar, Chief Executive Officer, Neeman Medical International.

Global pharma companies invest billions of dollars in R&D with the annual spends of the top 40 pharma companies being around $52 billion. A pharma company spends around $1 billion introducing a new drug, of which around $250 million would be spent on clinical trials alone. And of that, around $15-20 million would be spent on clinical data management (CDM) activities. India has a ready talent pool of manpower with the requisite IT expertise, and hence, it is regarded as a good place to outsource clinical trial data management. "The clinical data management market is in its infancy at the moment and the potential for growth is quite high," agrees Dr Kumar.

"Electronic technologies now enable pharmaceutical companies and CROs to expand clinical trial data management and integrate far-flung data centers around the world. With this shift, the role of data management is more important than ever, even as the nature of fundamental clinical data capture and database management has begun to change," says Mushtaq Ahmed, Domain of Bioinformatics and Clinical Informatics, Persistent Systems.

As more pharma companies conduct more Phase II and Phase III studies in India, the industry is no doubt in a growth phase, but the challenge is to maintain quality, even as the pace of growth picks up. Data must be of the highest possible quality to meet the accuracy of human trials and historically strict government regulatory conditions. "Clinical data management is one of the fundamental and often underappreciated processes that control both data accuracy and timelines of every trial," avers Ahmed. Clinical data management and data quality are thus key strategic assets of large pharma companies and CROs.

IT steps in

Therefore, archiving, analysing and maintaining clinical trail data are crucial to the clinical trial process, as the data needs to be presented in a suitable format for regulatory approval. And this is where Information Technology (IT) steps into the clinical trail process. Clinical trial systems require automating workflow related to clinical trial, patient consent and recruitment processes. This requires a complex data management system that is flexible enough to load and integrate data from disparate sources, support multiple analytical tools, and allow a user to search for data through complex analytical queries and display it in a variety of formats. With specifically designed IT-enabled clinical data management tools, data can be processed quickly and accurately, thus maintaining the quality of data.

IT has played a crucial role in every phase of clinical trials—faster submission of clinical trial data to FDA, automated validation leading to fewer errors, insightful analytics, detecting adverse events early. Integration of clinical trial data with lab data (microarray, proteomics, sequencing etc), tissue bank data and annotation data enables validation of lab generated hypothesis. This approach of connecting 'bench to bedside' is called ‘translational medicine’, and has become the major approach for cancer research worldwide.

Another important development that IT has made possible is in the field of pharmacogenomics. The sequence and genotype level details of individual trial subjects can be correlated with adverse events to find out the population that is best suited for a particular drug therapy and reduce the incidence of life threatening adverse drug reactions.

The IT advantage

The need mainly arose due to the fact that with the sudden surge in the life sciences industry, clinical and research analysts have found themselves swamped with large amounts of heterogeneous data being generated by automated high-throughput technologies.

Hundreds of clinical trials are being conducted at any given time. Investigators of these trials invest vast amounts of resources and energy into conducting these studies and often face daily challenges with data management and data quality control. The management, transfer and storage of data generated from these studies create several pitfalls for conducting successful clinical trials, including lack of real-time data reporting, lack of resources for recording the data, endless amounts of paper and lack of document storage space.

Rather than waiting months for study progress reports and interim and final analysis, investigators need quality data to be available for review and analysis in real-time, as well as the capabilities of relational database connections.

This resulted in a sudden increase in the need to streamline the flow of information and manage data efficiently. "It is here that the expertise of Persistent Systems comes into play ,since our core strength lies in the areas of data warehousing, data integration, data mining and data analysis, which are essential to this industry," says Ahmed.

Without efficient clinical data management, one would need to search through the whole database to retrieve a single record of any subject, which means wasting a lot of time and effort. Also, most manual records would have processed data only for trial completed subjects. This could lead to delay in submission to regulatory authorities. In this competitive world, a delay could translate into huge financial losses, especially if a competitor company is able to submit their data earlier to the regulatory authorities for approval.

With IT-enabled clinical data management systems, data can be processed quickly and accurately, while maintaining quality. Turn around time becomes much quicker and tracking data of trial subjects is much easier. In addition, quality can be checked at every stage.

Paper to paperless…

Earlier most of the clinical trials were based on paper clinical research forms (CRFs) but paper-based trials had many disadvantages, like poor quality of source data and large time taken for query resolution. These problems would delay database closure.

Over the past decade, pharmaceutical companies have introduced a number of initiatives to boost the productivity of clinical trials. One of these initiatives has been the rollout of electronic data capture (EDC) systems, which allow patients and researchers to enter their trial information directly, either in electronic diaries or online systems. With EDC systems, trials become much easier to process with the availability of online data entry and validation checks. The quicker the data collection, the easier the analysis and generation of reports as per FDA standards by using software like SAS, etc.

The industry was hopeful that these problems would be resolved with EDC systems but in recent years, investigators have become increasingly frustrated by such systems, which, they say, create more work than the old-fashioned pen and paper system did. For example, reliability issues have forced them to keep data both ways. Doctors and nurses also complain that they lack adequate training in the systems—a problem complicated by the fact that every company uses its own proprietary systems.

Other efforts to improve productivity include the adoption of new scientific approaches that enable pharma companies to refine their designs for trials from one stage to the next. In addition, companies have improved their technological capabilities, especially connectivity at clinical locations by allowing trial managers to keep tabs on the retention of patients and the progress of trials. They have also improved their ability to conduct trials on a global basis, by vastly increasing the pool of researchers and patients. And they have adopted more disciplined procedures for managing trials, in some cases, borrowing techniques (including 'stage gates', which set firm deadlines for gathering data and refining the goals of subsequent stages) from product design.

Outsourcing opportunity

Another trend is outsourcing of data management activity. Previously, clinical trials were very few and that too, limited to big pharma companies so this activity was managed in-house. But with the signing of the TRIPS agreement, there is a sudden spurt in the clinical trials taking place in India. To cater to the management of all this clinical data, a pharma company has to set up a full fledged clinical data management system, which involves making more employees technically adept in clinical data management, setting up computer systems, network connectivity, etc. Therefore, a pharma company would have to invest considerably if it were to set up its own clinical data management centre.

Rather than move away from their core competancies, pharma companies (especially small and medium sized ones) have realised it makes more business sense to outsource this activity to niche service providers like Neeman, who cater to the clinical data management needs of the pharma companies.

India as a country is also becoming a clinical data management hotspot. Most of the multinational pharma companies placed in the US and Europe are looking towards India for outsourcing clinical data management services, so that they can save on cost, without compromising the quality of data management. Therefore they are outsourcing their clinical trials and data management processes to full fledged service providers with domain experience like Biostatistics, data management, data base designing, statistical programming and medical writing. Indian clinical data management companies are already following global regulatory norms like CDISC, HIPPA, ICH GCP guidelines as per FDA requirements.

Speedbreakers

Clinical data management has many challenges. For example, in EDC trials, CROs have to establish and maintain connectivity throughout the trial, and ensure that no hackers enter into the system and there is no loss of data. As there is no source data in EDC trials, this becomes a very important step. "We at Neeman take constant data backups and we have a mirror server, which ensures that there is no disruption of service in case of any eventuality," says Dr Kumar.

"As any other industry, we also face attrition of the employees but we ensure employee retention by encouraging employees to enroll for higher education. Performance incentives and motivation gifts are provided, based on employee performance on any project," informs Dr Kumar. As the IT industry progresses towards new technologies, one has to keep constantly updating skills. Therefore there are continuous training programs conducted for employees at Neeman for the same.

Future secure

A significant opportunity to speed up clinical trials awaits pharma companies that build on the foundations of the first wave of EDC systems. Changes of this scope are never easy, and legacy systems can act as a drag on new solutions. The role of data management, which is more important than ever, is becoming more crucial, even as the nature of fundamental clinical data capture and database management has begun to change. The clinical trials industry has already moved onto the fast track. However, maintaining quality at high speed is as crucial as keeping pace. IT could well be the differentiator, which will help the industry navigate higher standards of quality, efficiency and service.

arshiya.khan@expressindia.com