For years, we’ve been mocking it. There have been unkind remarks. Words like antique, prehistoric, pre-computer, Elizabethan. “Dickensian” is our favorite. We’re talking about ... paper.
Then we found ourselves on the phone with a gentleman who makes a good argument for paper. “We provide immediate information for the sponsor or CRO. But we keep it very simple for the doctor,” says Guillaume Juge.
General manager of 40-employee Kayentis, which is based in Gif sur Yvette, France, southwest of Paris, Juge explains that his company’s system for clinical trials includes specially-printed paper and a pen-based scanner designed to record the delicate movements of the human hand.
The technology was pioneered by HP and Anoto but refined by Kayentis. In addition to backing from the French government, the company has a U.S. office, which Guy Maestre (a former Wyeth executive) is running as VP of U.S. operations.
EDC & Diary
Besides providing a paper-and-pen alternative to an electronic data capture (EDC) system, Kayentis also supplies forms and pens for patient diaries. Its system uses documents with tiny, specially printed dots that uniquely identify each sheet.
The scanner-pen automatically sends data into the database, which can reduce the need for tedious human data entry, a sore point for clinical sites. Each piece of Kayentis paper has a pattern of dots to link it to a particular site, visit or patient. So there is the potential for cleaner data than with other systems that have three or four steps between the collection of data and its arrival in a database.
The Kayentis paper looks ordinary. But it is not really similar to the pile of papers in your office just now. The company has found a way to make paper, dare we say it, sexy. And database-friendly. Every note and squiggle made by the pen is time-stamped. In the U.S., Health Decisions offers a similar technology.
Says Juge: “Once something has been written down on the page, it will go straight to the exact place it was supposed to be stored in. We can print millions of documents and each and every page will go where it belongs. Once you have defined in the beginning that this document belongs to that patient, the entire document will be associated with that patient, that center, that country, that study.”
Juge adds that some of his customers have tried traditional EDC and are less than happy. Dissatisfaction with those systems is driving customers back to a new type of paper, he says. The French pharma Servier is a Kayentis customer, and has been increasing its orders with Kayentis. So are Actelion and the Pierre Fabre Research Institute. More than 50 trials using the Kayentis technology have been started and are at various stages of completion.
The crux of the Kayentis pitch is that conventional EDC is not a big advance for productivity. Says Juge: “The doctor prints the page and asks the study nurse to type it. There is an average of two weeks before it is in the system,” he says. “Most of the doctors are still reluctant users of classical EDC in front of their patients.”
Juge points out that many EDC systems still use significant amounts of paper for a combination of emotional and regulatory reasons. Says Juge: “As far as I know, paper is still mandatory on site. Even if you work with an electronic case report form (eCRF), you have to print the pages. You have to print the paper source documents.” There are patient diary firms that would dispute the primacy of paper records, but (in the U.S. at least) the FDA has declined to issue guidance to resolve all lingering confusion on this point.
Complete Esource Defeat
A digression may support Juge’s argument. It is now unusual for people supporting clinical trials to talk about “e-source.” That once-popular buzz word, referring to systems without paper source documents, has fallen out of favor.
Mixing and matching paper and digital data would probably send other industries (brokerages, airlines, retail stores) to their knees. But a hybrid paper-digital landscape is the reality for most physicians. A pharmaceutical industry that leans on those doctors as crucial partners has no choice but to use the same tools.
Starting with a generic CRF, Kayentis works to tweak the CRFs for a trial so that they have as many check boxes and other easily scanned elements as possible. Data managers or clinical research associates may be able to confirm the computer’s transcription of some elements.
A full digital image of the scanned sheet can be reviewed after the data are collected. On occasion, the physician who saw the patient must verify that the handwritten word “colonoscopy” was correctly scanned into the system. Says Juge: “In some cases it is the doctors themselves who verify the data and make sure it is compliant with what has been written down.”
Judging by a May 2008 article in the journal Contemporary Clinical Trials, the accuracy of the system appears noteworthy. The article’s title: “Data capture by digital pen in clinical trials.” Academic scientists lead by Philippe Ravaud in Paris studied the Kayentis system. They compared the automatically-decoded writing with traditional, Dickensian double data entry. Just 0.38 percent of 5,022 data points were wrong. In general, the scientists say, 16 percent of the larger amount of 12,462 data points had to be manually verified by humans. So the system got a lot right.
“There is no relevant difference between the number of errors for the DP [digital pen] and the double manual data entry systems,” the French scientists wrote. “Data are potentially available for data management and analysis in a matter of seconds.”
Rest Of World
Even with the human review of the automatic rendering of the clinician’s handwriting, Juge says, Kayentis can deliver data rapidly. “For the studies we have been doing, it is obviously far faster than paper,” he says.
Because of limited bandwidth requirements, the system is well-suited for nations with poor telecommunications infrastructure. “The pen captures the small dots,” says Juge. “The data flow is very limited. It is very easy to implement the solution in developing countries.” It can also scale for global trials, he says, supporting ten thousand users at once. “No other company has that kind of track record,” he contends.
In some respects, the Kayentis system is an EDC system. There are edit checks; access to the data via the web; an audit trail; programmable alerts sent by email; and data exports to Excel or XML files. “We have all the features of EDC,” says Juge.
Having said that, Juge sounds equally excited about using the system to collect electronic patient reported outcomes (ePRO). For some patients, he says, a smartphone or personal digital assistant is an intimidating, confusing device. Not so with his technology. “You can give a pen and paper to any type of person. You don’t have to explain anything. You just have to take the cap on and off,” he says.
Rather than try to deny the existence of paper in the clinical trial landscape, the Kayentis system exploits it. “We combine the best of two worlds,” says Juge.
Editor’s note: This is an article about another rethinking of paper from this year’s Society For Clinical Data Management Meeting.d9A2t49mkex