Push for paperless clinical trials

Modern medicine would make precious little progress without clinical trials, so it is surprising that such an essential process can often be bogged down by inefficient processes. More than ever, there is a need to have trial results published quickly and to the highest possible degree of accuracy, yet the paper trail is voluminous and cumbersome.

Clinical trials are often inefficient, paper-based processes, and as their complexity grows, their efficiency declines. With outsourced partners heavily involved in key stages of clinical trials, and with more sources of data than ever before, managing clinical data can be a huge and complex task.

In today's high-tech world, where electronic data is the currency of every individual - let alone sophisticated pharmaceutical companies - it is no surprise that clinical trial data has been a key focus for technology vendors serving the pharmaceutical market. What is surprising is that for all the work that has been done on electronic data capture (EDC) and clinical trials management systems (CTMS), the industry is not further down the road towards completely paperless clinical trials processes.

Challenges of speeding up time-to-market

Progress has certainly been made in developing systems that improve data capture and management, but challenges still remain for progressive pharmaceutical companies that are eager to improve efficiency, and shorten the timescale for drug development and delivery. As well as speeding up time-to-market for new drugs and making the approval process simpler, these companies also understand the costs involved in managing the huge volumes of paper that clinical trials can generate.

"The volume of data is the biggest challenge in data management," says Susan Howard, assistant director of clinical data management at GlaxoSmithKline (GSK). "I started out in 1994 when there were maybe two sources of data. Now, there can be as many as ten sources, including imaging data, multiple labs and diary data. Parts of the process that are outsourced add to the number of sources. The complexity of data management has increased significantly."

Work still to be done

Howard, who is also chair of the Society for Clinical Data Management and is active in the Good Clinical Data Management Practices Committee, knows well the challenges that systems vendors face in developing EDC and CTMS technologies. She has seen the concept of paperless trials discussed widely throughout the industry for many years, and appreciates that technology vendors have understood the challenges and, in some cases, come up with effective and intelligent solutions. Yet she knows there is a lot of work still to be done.

"The issue needs a lot more work by EDC vendors to solve the problem," explains Howard. "No one solution has it all. A system may have one capability that you want, but you don't find everything you need in one place. At GSK, when we upload data to our safety database each night it needs reconciliation with items like concomitant medications and serious adverse labs. Some systems do data integration, another has a good local lab tool, and there is one that gives you a tool to create PDFs of case report forms. It should be possible to integrate all of these into a general platform where data can be fully integrated."

Everything to gain

The potential cost savings and efficiency gains from reducing the amount of paper handled in clinical trials - whether it is regulatory documents, protocols, contracts, patient records or any other kind of data - are clear. Every big pharmaceutical company wants to progress towards a more technology-based clinical trial submission process, but in such a highly regulated industry, there are hurdles to overcome; for example, EDC and content management technologies have to be highly secure, as well as scalable and robust. Furthermore, interoperability is a key issue. As more partners become involved in running clinical trials it is essential that their systems can work alongside each other without a hugely laborious and time-consuming integration process.

A white paper released in 2011 showed that the clinical trials could not only be initiated more quickly, but also that they performed at a lower cost using technological components such as digital identities, digital signatures and cloud storage of electronic documents. The paper covered a 2010 pilot study run by the National Cancer Institute (NCI) and Bristol-Myers Squibb, in which researchers used interoperable digital identity credentials that allowed them to sign off electronic documents with an authenticated digital signature. These documents were stored in the cloud - virtualised data pools hosted by third parties and accessed through web-based interfaces. As such, the documents were secure, but could be quickly accessed by the researchers.

Combining such technologies with EDC, which simplifies the collection, storage and transfer of clinical trial data, can drastically reduce the number of paper-based processes. NCI estimated that its clinical studies required 100,000 pages of documents in 2010, which meant a great deal of time and money was spent faxing or mailing these papers to the FDA.

Taking the best from each system

EDC solutions have probably had the biggest impact so far on the amount of paper used in clinical trials, as they concentrate on the key processes of collating, organising and verifying data for the preparation of case report forms, which hold the data on every participating patient at each site. Yet changes in the reporting requirements of the FDA have moved in the opposite direction, meaning that EDC has not had as big an impact on reducing the paper trail as was once imagined.

Yet EDC is not the only breed of system that has been used to make clinical trials more efficient. CTMS can plan and manage trials more effectively, assisting with site selection, recruitment of patients, budgeting, and tracking constituent activities. The impact of these systems on the amount of paper in a trial, however, is much lower.

The priority now, it seems, is to take the best from the individual systems on the market and bring them together in a cohesive way to meet the needs of pharmaceutical companies and regulators.

"Things will not get simpler in the future. The complexity of clinical trials will only grow," says Howard. "No one system meets all needs, and discussions are usually on a company-by-company basis when you do EDC selection. Companies know the quirks of a familiar system so they will stick with it, but they are not looking to future trends. One vendor has an industry forum about data integration, but it could take a couple of years to produce anything, and the problems may have changed by then. The issue of what is needed from electronic data collection is often raised at industry conferences because manual reconciliation of data is a ridiculous idea."

For Howard, the approach needs to be coordinated at an industry-wide level, and the most useful step would be to introduce common standards that focus the minds of vendors, pharmaceutical companies and regulators on shared goals.

Setting the standard for clinical trials

Establishing standards that apply across a process as complex and as highly regulated as pharmaceutical clinical trials may seem like a huge task, but a lot of work has already been put in to make this happen.

"The biggest hurdle is standards," says Howard. "We should all be using the same guidelines, such as the laboratory data standards from the Clinical Data Interchange Standards Consortium [CDSIC], but at the moment we give the specifications on how we want our data to the vendors and they design to that. The process is specify, then programme. The problem with that is that if you have co-development then you have to learn new standards, which is inefficient."

The CDSIC has long been working on open standards, which are widely seen as having the potential to reduce the costs of EDC. Its operational data model (ODM) is designed to facilitate the archiving and interchange of metadata and data in clinical research, and to simplify the management of data from multiple sources. The ODM allows the set-up of an EDC system and a database to enable the automatic creation of electronic case report forms. Usually, these elements have to be set up manually for each new study, with the forms being designed from information provided by the trial's sponsor in a bespoke fashion.

"The CDISC standards have been around since 1999, and the FDA has implied that it would push for these standards," says Howard. "It did do draft guidance for standards, and has said that it wants standardised data for submission, but this was not made mandatory. Guidance for industry submissions in electronic format has been a long time coming. They are just out, though they have been talked about since 2001. Response to the guidance is going to the FDA. What we need is all sides - vendors, pharmaceutical companies and regulators - to work together."

All about the data

A key hurdle to overcome is the use of electronic health records, which doctors use to track the treatment of their patients. These represent a huge and valuable resource for running clinical trials, but EDC systems do not interface with electronic health records easily. Standardisation has long been seen as the answer, but there has been little progress made in terms of integration. The benefits are obvious, but so far this has not provided sufficient momentum for a solution to be found.

"Lab vendors have the most to gain," says Howard. "They could do more trials at a lower cost. For me, this is a priority and the only way to be efficient is to have standards in place. Clinical teams don't always recognise the importance of standards, but designing an electronic case-management form should not be a time for creativity. You need standardised responses. It is all about the data, and the need to get a study out in a timely fashion."

There are problems, but these are greatly outweighed by the benefits, according to Howard.

"Ultimately, if we are to use electronic health records then you will need to have standards across the industry," she says. "That data can't be customised as easily to suit our needs."

There is certainly an awareness across the industry, and among the technology vendors that service it, that more needs to be done to make clinical trials more efficient, which means cutting out the paper and automating as many stages as possible. The will to work towards a solution is also there, and it has provided the impetus for all the good work that has been done so far. Yet standards are still a stumbling block.