Clinical Research Technology 2003

It has been eighteen months since this column has reviewed developments among the clinical research IT vendors and their applications. Much has happened since – not so much in terms of technical functionality, but in the configuration of the vendors and the apparent areas of interest among sponsors and CROs.

The state of the clinical research IT vendors remains one of constant change, but in most cases this tumult has had surprisingly little impact on their customers’ ability to derive value from their applications. What is clear from the sponsor community is that, despite a general slowdown in purchasing of all kinds in 2002, the need for updating and innovation in their clinical research IT is stronger than ever.

Markets & Vendors

EDC While there has been steady vendor turmoil in the electronic data capture market, there has also been steady progress in functionality and sponsor acceptance. The percent of trials using EDC is continuing to rise, even though several circumstances mitigate against this trend: the rise and fall of individual vendors, the persistent inadequacies of vendor offerings, the slow pace of internal change at sponsors in order to use EDC properly, and the failure of sponsors to document objectively why EDC is advantageous, particularly in financial terms.

Phase Forward has lengthened its lead in the EDC marketplace since last we wrote, this despite the major challenges in incorporating the ClinSoft CDMS and AES product lines. The “second tier” of vendors all reported acute financial distress in early 2003: CB Technologies filed for bankruptcy, Datatrak was delisted by NASDAQ, and Etrials Worldwide (newly formed by merging Araccel – itself a merger of Technilogix/MiniDoc/Onsite Systems – with Etrials, Inc.) found itself undercapitalized and slashing salaries. This has left some sponsors at a loss as to where to turn, and has given EDC skeptics fuel to fan the flames of EDC’s evanescence. Such observers confuse the management and financial misfortunes of these companies with the value of their products and services; throughout EDC’s history, it has been the immaturity of the vendors and the sponsors trying to use them that has caused repeated corporate failures, not some essential flaw in the technology principle.

As older second tier vendors falter, there is another phalanx of newer vendors ready to take their place. We can only hope they are not sacrificing themselves on the same fatal sword, but instead have learned from those before them. From what we have observed, we are unconvinced. Meanwhile, increasingly we see CROs acquiring, adopting or developing their own EDC tools, and offering them to sponsors wary of having to make a vendor choice. For at least the short-term, this is likely to be a very large source of EDC trials.

There are still too many vendors, but the technology is coalescing around some version of Internet-based tools, with or without offline options, with or without XML, usually with an eye to CDISC standards. While most observers assume the EDC market will consolidate, there seems to be an insatiable desire among entrepreneurs to start yet another EDC vendor. Meanwhile, those sponsors who are steady in their own focus, who are getting their company to understand electronic clinical trials, are moving ahead, with or without yesterday’s vendor.

CDMS It has been striking to us in our practice to see how much interest there is in acquiring new clinical data management systems – an arena thought passé with the advent of EDC. In truth, all of the acquisition situations we have seen always do include EDC as a component of CDM, which is a welcome maturation of both market segments and the industry’s attitude towards them.

The continuing need for upgrading or acquiring back-end data repositories is a reflection of several factors: dissatisfaction with smaller or less robust vendor offerings; the final death of legacy systems, now expiring because of a failure to be 21 CFR 11 compliant (if for no other reason); the growing dissatisfaction of smaller companies (who have outsourced CDM services) with the idea that their data repository is not internal; and the grinding competition facing CROs who need to constantly upgrade their offerings.

In this market niche, Phase Forward’s Clintrial and Oracle’s Oracle Clinical remain the dominant applications, with few new compelling ideas being offered by other vendors except a proposition based on price.

AES Fortunately for the tired IT manager, and lucky for the pharmacovigilance executive, the adverse event tracking and reporting market is highly stable, still being led by the three major vendors – Phase Forward (Clintrace), Aris Global (ARISg), and Relsys (Argus). Since we last wrote, each has enhanced their products to accommodate the new European requirement to report Individual Case Safety Reports electronically using the ICH’s E2B format.

In addition, vendors are offering the external gateway products required to transmit these reports to the European authority according to the ICH’s ESTRI standard. Several sponsors, especially those with joint marketing agreements with other sponsors, are planning to use these standards to exchange safety data with each other.

CTMS No such luck in the clinical trials management software space, which remains the most confused, fragmented, yet critical component of the clinical research IT world. Since last we wrote, many new vendors have offered up applications which serve users all across the spectrum from individual investigators to large pharma planning departments. It is hard to find two applications in this space which cover the same set of users or needs. This is one significant clinical research IT component where companies still seriously consider building their own, and understandably so.

The most commonly used application amongst large pharma, Impact, which had been offered by FW Pharma Systems, a spinoff from a UK applications company, was recently purchased by the Perceptive Informatics unit of the CRO Parexel. It remains to be seen how well this will play out in the market. Siebel Systems, best know for its salesforce applications (“CRM” – customer relationship management), is beginning to make inroads in this space as well, as they try to evolve a custom application into a standard one at a reasonable price. The stock price and financial woes of the parent company may have an impact. Besides these leaders, primarily focused on large customers, sponsors and CROs have a myriad of choices, including designing their own.

EPD The electronic patient diary space shares characteristics with the EDC market (vendor upheaval) and CTMS (different sponsors with different needs). This space is increasingly hard to describe: does one include IVRS (interactive voice response) in the same market as handheld PDAs? Are tools for investigator-administered questionnaires (implemented through Tablet PCs or touchscreen computers) in the same market? How do we categorize specialized little hardware, or wearable devices? Are we talking about “real time” patient experience, patient-reported outcomes without regard to timing, or investigator recording of “soft” patient experience?

With such a breadth of uses in clinical research for soft patient data, one almost faces a scenario of one vendor per niche. In the generally accepted definition of EPD (handheld PDAs to be used by patients outside of the clinic in “real life”), there are a handful of key competitors – invivodata, Etrials Worldwide, PHT, CRF Box, Clinitrac and others – who have all worked hard to improve their offerings over the past year and to keep up with rapidly changing technology. For instance, now that a Palm Zire can be had for under a hundred dollars, the old objection to EPDs that the hardware is too costly no longer applies.

Vendor turmoil plagues the EPD space as well, although less dramatically than in EDC. PHT has struggled for years with very high management turnover; Etrials Worldwide’s troubles were mentioned above, and who knows how this will affect its EPD offerings, which are secondary to its EDC work.

The exciting development in the EPD space is the growing recognition among sponsors and regulatory agencies that a) paper diaries are not reliable instruments, and b) electronic diaries can help sponsors prove things they could never really prove before. This development provides hope that this pocket of clinical research inefficiency may yet be eliminated.

Other Niches

There are at least two other interesting spaces to watch in the clinical research IT market. One is the area which used to be called “trial simulation” or “CATD” (computer-assisted trial design). Companies like Silico Insights, Spotfire, Cytel, Pharsight and Innaphase, among others, are all trying to apply creative conceptions of statistical analysis, scenario theory, pharmacogenomics, and untapped sponsor data to try and refine the preclinical and clinical development program for maximum efficiency and more rapid decision-making.

The other space is much more down-to-earth and mature: that of eSubmissions. Those vendors (usually document management suppliers originally) such as Liquent, Documentum, and CDC Solutions are rapidly adapting their tools to the requirements of the CTD (Common Technical Document).

Sponsors Still Hungry

Despite the economic constraints on the biopharmaceutical industry felt throughout the last 18 months, or perhaps because of them, sponsors remain hungry for improvement in their operational efficiency across the board. Many hope this efficiency can be gained in part through information technology. For every company whose plans have become less ambitious, there is another who is pushing themselves more aggressively to modernize. The projects may take longer to be approved, and their scope may be trimmed back or implementation stretched out, but the march forward is inexorable. Every biopharma still has so far to go in making clinical research more efficient and effective, we will see continuous investments in information technology, as a collateral component of these efforts, for years to come.

The more thoughtful of sponsors and CROs recognize that individual application decisions can no longer be made independently of other application choices. The need for integrating data amongst these applications, reducing re-entry and reconciliation, and gaining synergistic benefits from all this IT investment, are all driving more and more sponsors to try to develop a strategy or roadmap that can rationalize the purchases. This is an excellent approach, as long as the roadmap is iterative and not an excuse for rigidity or political control.

The keys to success in technology adoption remain the same: know why you are acquiring the particular technology; remember that the effort has much more to do with process than software functionality; and get your organization accustomed to a work environment of continuous technology change.