OR WAIT null SECS
To ensure that everyone involved recruiting pediatric subjects is on the same page, maybe it's time to go to the videotape.
With the point of a cursor and the click of a mouse, children of the Information Age are completing their homework, chatting with friends, and delving into the virtual reality of multiplayer video games. Even as some parents vocally oppose the disproportionate amount of time their children—especially teenagers—are spending online, the day-to-day use of multimedia communications and entertainment continues to grow. Child's play once consisting of outdoor games and indoor creativity has given way to Web surfing, e-mail, and instant messaging. For many, books have been replaced by reality television shows or downloaded DVD movies. While the radio was once a favorite source of music, teens and pre-teens (at their own legal risk and that of their parents) are now more apt to download their favorite MP3s off the Internet. The reality is today's children are a technology-driven, technology-savvy group. As such, they are both familiar and comfortable with multimedia technologies in their various forms.
Figure 1. 3-D graphics, on-screen text, and narration help subjects understand complex medical information, such as an immune system over-reaction in subjects with atopic dermatitis.
Through these advances in technology, the way children learn and absorb information has changed, or perhaps is simply becoming better understood. In years past, teachers primarily used textbooks and lectures to educate their pupils. Now, technology has reached into the classroom as more and more educational institutions supplement traditional teaching methods with multimedia instruction.1,2 Studies find multimedia education improves both comprehension of the lesson material and students' interest in the topic, which translates into better retention of the information.3 With this understanding in mind, how can researchers harness technology to improve informed consent and recruitment in pediatric clinical trials?
This article studies the current process of educating pediatric subjects and their parents about a given trial. A discussion of clinical trials utilizing multimedia technologies in the consent process follows. The results of these studies—namely an improvement in subjects' comprehension, recruitment rates, and retention—are the harbinger of a new trend in the education of pediatric subjects.
For a pediatric subject to enroll in a trial, the "consent dyad" (parental informed permission and the child's assent) must be fulfilled. While one might assume this process to be similar to that of enrolling adult subjects, successfully consenting and enrolling a pediatric subject is far more challenging.
Figure 2. Pediatric multimedia presentations hold potential subjects interest and facilitate learning better than text-based assent documents.
Consider first the current informed consent process, which uses a text document to educate parents about the trial's risks, possible benefits, expected results, and alternatives. This form is usually written at a single reading level, automatically making it too condescending in tone and verbiage to some parents and too difficult to understand for many others. The latter concern is illustrated in a 2003 study published in the New England Journal of Medicine.4 Dr. Michael Paasche-Orlow and his associates at Johns Hopkins University found that in the United States, only 8% of institutional review board (IRB)-approved informed consent templates are written at an appropriate reading level. While the IRBs of most medical centers stipulate that consent forms be written at a reading level ranging from fifth- to eighth-grade, Paasche-Orlow found that the average informed consent template is written at nearly an eleventh-grade level—with some written at college reading levels. This is particularly egregious when one considers that nearly a quarter of American adults are functionally illiterate, about half read at or below an eighth-grade reading level, and the average Medicare subject reads at the fifth-grade level.5 It is unsurprising, then, that 14% of potential subjects do not even read—or attempt to read—the informed consent document.6
With the informed consent process in its current state, many parents are unable to fully comprehend the consent information. Without a full understanding of a trial, parents are far more likely to prohibit their child's participation. This refusal stems chiefly from the uncertainty and fear a lack of understanding generates. Herein lies the first challenge of recruiting pediatric subjects—overcoming parents' disparate levels of health literacy.
The second challenge of pediatric recruitment is proper education of the child. It is widely known that pediatric subjects are not to be viewed simply as "little adults." This mandate extends beyond side effect profiles and dose measurements to include how the pediatric subject is educated about the trial. If the parent does grant informed permission, getting the child's assent is more than a mere formality. As part of this process, researchers must give the pediatric subject an informed assent form, based on the child's assumed reading level. While a few different versions of the assent form may be written, the wide range of reading levels amongst pediatric subjects can significantly hinder the assent process (i.e., forms said to be "age-appropriate" do not necessarily equate to forms of the child's actual reading level). For example, a 17-year-old senior honor student will likely ridicule an informational assent handout written for the average high school student. Conversely, subjects in elementary school or junior high school—especially those for whom reading is a challenge—may have considerable difficulty comprehending information written at their grade level or even lower.
Figure 3. Tablet PCs offer a touchscreen interface that is easy for healthcare providers and subjects to navigate.
Pediatric subjects must also have the opportunity to discuss any questions and concerns with the parent and study coordinator or investigator, and then freely decide whether or not they desire to participate in the trial. This presents a formidable challenge, as age-related behaviors—ranging from the child's desire to please the parent to tantrums and teenage rebellion—can all affect the pediatric subject's decision-making process. Parents must do their best not to unduly influence the child's decision one way or the other.
Ultimately, the challenges of effectively educating both parent and child are myriad. If one reviews the literature, it is clear that the current consent process fails in its ability to fully educate, validate comprehension, and consistently deliver the same information to each subject. If written education continues to be the industry standard, multiple consent forms—each at different reading levels—will be necessary. Researchers will have the burden of determining which form is most appropriate for each parent and pediatric subject. The investigator and research team must also ensure the reader's comprehension of the trial material. These challenges and responsibilities require clinical trial professionals to expend considerable time and resources toward the education of pediatric subjects and their parents.
Given the significant challenges of properly educating prospective subjects, it is unsurprising that in a study of subjects' comprehension, 70% of participants felt they had no understanding whatsoever of the trial they were in, or only "somewhat understood" the trial.7 Based on these data, subjects' comprehension of protocol and consent information for many trials is clearly insufficient. The informed consent process must improve for clinical trials industry-wide, but particularly for those involving the vulnerable population of pediatric subjects. But who will effect this change?
Ultimately, the principal investigator is responsible for providing parents with the information they need to give truly informed permission. The investigator is also charged with providing age-appropriate assent materials to the child and explaining the trial in terms he or she clearly understands. However, this can be a time-consuming and difficult task. Many investigators and study coordinators have only the basic educational tools—such as written assent forms—and lack experience in educating children in an effective, understandable manner.
However, investigators alone are not fully culpable for the deficiencies in the current educational process. Principal investigators often receive part, if not all, of their educational information from the sponsor of the trial. This frequently comes in a single, one-size-fits-all format. Such an approach is deleterious to the true intent of patient education and informed consent on several levels, as all pediatric subjects (and their parents) are not created equal. As pharmaceutical, medical device, and biotechnology companies have traditionally provided educational information to the research sites, these sponsors must take greater initiative in ensuring subjects' comprehension of the trial.
One proposed method to improve pretrial education is through the use of multimedia presentations.
There are several key advantages to using multimedia education for pediatric subjects and their parents. Just as in watching television, viewers of varying age groups and intellectual capacities can understand the information in the same presentation. This is because multimedia incorporates multiple learning methods and the viewer's comprehension does not rely solely on his or her reading level. Whereas traditional informed consent delivers trial information through limited learning methods (reading and discussion), multimedia presentations utilize these methods plus hearing, seeing, and interacting. Such presentations use narration, video, 2-D and 3-D graphics, animations, and photos to educate the viewer. On-screen text is often used to highlight key points of the presentation. And since the amount of on-screen text is minimal, it is far easier for researchers to gauge which version of the presentation a given subject or parent should watch. This amalgam of teaching methods stimulates many of the senses, promoting a deeper understanding and stronger retention of trial information.
With some systems, the viewer can answer true/false or multiple-choice questions during or after the presentation to demonstrate his or her grasp of important concepts. This not only allows the viewer to interact with the system (which enhances learning), but provides the research team with an objective measure of the viewer's comprehension of the presentation.
Various studies prove the effectiveness of this type of education in improving several aspects of the consent experience. Multimedia patient education:
The end result of these benefits is a more satisfied parent and pediatric subject. This improved satisfaction serves to enhance the subject-researcher relationship and foster a sense of trust and understanding, both of which are critical to successful education, recruitment, and retention.
When a sponsor or research team decides to implement technology in the consent process, there are two items to be particularly mindful of—the actual creation of the content and the platform through which the content runs.
With the advent of digital technology, multimedia content is becoming more commonplace and also more flexible. However, not all content is created equal. Sponsors and researchers who desire to use multimedia education will need to assist in the content development process. As there are very few companies specializing in multimedia informed consent, most vendors will require oversight to ensure the accuracy of the presentation and that 21 CFR Part 50 requirements for informed consent are met.
Most content is developed in a format that can be easily used with a variety of platforms such as videotapes, CD-ROMs and DVDs, Internet sites, and customized software programs. Just as all content is not of the same caliber, the quality of multimedia platforms on the market varies considerably. When evaluating different means of disseminating educational content, one must scrutinize each platform to ensure it will meet the needs of the specific subject population and the research site. In many ways, choosing the correct viewing platform can be a more important decision than choosing the right content development company. Key factors contributing to the quality of a platform include:
A platform's level of interactivity influences the potential subject's learning experience. The degree of interactivity in technology-based education ranges from the low interactivity of videotapes to highly interactive customized software.
Videotapes are a one-dimensional platform in the sense that every subject views the same content, regardless of his or her entering health literacy. There is little room for interaction between the subject and the video—other than the ability to pause the presentation and rewind it as needed.
CD-ROMs, DVDs, the Internet, and customized software allow for more interaction between the viewer and the presentation. These platforms allow the subject to choose—within reason—what information they will see. The most interactive platforms include customized educational software, such as Vital Consent by Keris, Inc. (www.kerisinc.com). These programs offer parents and pediatric subjects a level of control and interactivity not found with videotapes or even CD-ROM programs. Upon learning about the opportunity to participate in a trial, parents can watch a pediatric assent presentation with their child and also watch a more detailed multimedia presentation designed specifically for the parent or guardian. The software can be customized to provide additional information specific to the subject's age, ethnicity, and medical condition.
Presentations for the adult caregiver include a main presentation containing all the pertinent informed consent topics specified in 21 CFR Part 50. An optional reference library, containing helpful information on the child's health condition and about clinical trials in general, can also be included. In both the main presentation and the library, the parent has the option to pause the presentation, re-review pertinent clips, or skip clips altogether if the information is already well understood. By pressing a "question button," the viewer can type his or her question and save it for later discussion with the investigator. After watching a final mandatory clip that summarizes the main points of the presentation, parents then answer a handful of questions to verify their comprehension.
Pediatric presentations can be delivered in an interactive game format, where the child is able to help a protagonist character in accomplishing a specific objective. To pass the varying levels of the presentation, pediatric subjects watch brief clips on different aspects of the trial and then answer multiple-choice questions. Examples include going on a treasure hunt, where each correctly answered question takes the main character to another part of the map, or earning different parts of a rocket ship to help an alien friend return to his home planet. This type of interactive "edutainment" is found to hold children's interest and enhance their retention of key learning points. To address the varying reading levels of pediatric subjects, the presentations can be customized to display differing amounts of on-screen text. When the subject is set up on the computer, his or her age is entered and the software automatically adjusts the presentation as needed.
The importance of interactivity is well understood among producers of clinical trials software. "The key to any effective content and platform is empowering potential subjects—giving them some latitude in deciding what information is important to them and what is not," relates Art Schoenstadt, MD, COO of Keris, Inc. "There is certain information that must be covered in the informed consent process, and other optional information that may be helpful to certain individuals. We have learned through over 13,000 patient encounters that there is no way to tell what information one particular individual will find necessary and another will not."
The flexibility of a multimedia platform determines how rapidly content can be updated, and how well information can be personalized to meet the specific needs of the IRB, research site, and sponsor.
It is no secret that trial protocols are subject to change and that different IRBs have different nuances as to what they will and will not approve. A flexible platform must take into account these realities of the clinical trials process. Videotapes, CD-ROMs, and DVDs do not allow for this flexibility, as they become outdated almost as soon as they are distributed. Any change in the protocol means new discs must be created and shipped to the different research sites, oftentimes at considerable expense in dollars and time. In contrast, continued refinements to the Internet allow developers to quickly update content in a cost-effective manner. This holds true for content that is viewed via an Internet browser, such as a clinical trials Web site, and also for customized software programs that allow real-time updates through the Web.
Flexibility is also manifest in a platform's ability to personalize or modify the multimedia presentation. Such flexibility occurs when content is database driven, which happens with Internet-based platforms or customized software. When a viewer is set up on these types of platforms, certain demographics such as age, sex, ethnicity, and location can be entered to ensure the individual views the most appropriate version of the presentation. This customization also takes into account any of the subject's pre-existing health concerns and presents relevant content as needed. The flexibility found in database-driven systems allows personalization to occur at individual research sites, such as listing names and photos of the investigators, study coordinators, and research site itself.
A final aspect of a platform's flexibility is its mobility. With the advent of Tablet PC computers, multimedia trial overviews or consent sessions can take place at various locations throughout the clinic and hospital setting. This holds true for CD-ROMs, DVDs, customized software, and wireless Internet connections. Videotaped presentations are still subject to the constraints of electrical outlets and the necessary space for a TV/VCR. Advances in Internet capabilities make it possible for families to review interactive presentations in the comfort of their own home—perhaps including the second parent if he or she was absent for the initial viewing in the clinic.
Advanced multimedia programs can objectively measure the effectiveness of the interactive presentations. When using videotapes, DVDs, and even some CD-ROMs, researchers must rely on their own discussion with the parent or pediatric subject in order to gauge comprehension. Sponsors are not able to objectively measure differences across sites. Customized software gives investigators and sponsors various tools to evaluate comprehension both objectively and subjectively. Objective measures include reports of the amount of time spent watching and interacting with the program, and the different optional topics that were viewed, re-reviewed, or skipped. Effective technologies ask viewers to answer true/false or multiple-choice questions to demonstrate their understanding of key learning points. While admittedly not a perfect means of ensuring understanding,
the viewer's answers do serve as an objective gauge of comprehension. In the case of pediatric subjects, comprehension can be evaluated through their responses to questions that come in the form of small games or puzzles that represent different aspects of the trial. Subjective measures include electronic questionnaires administered before and after the educational session. These questionnaires can deal with subjects ranging from self-reported knowledge levels to anxiety levels to satisfaction with the consent session.
Through such feedback, multimedia programs can provide a continuum of learning that extends beyond the viewing of the initial presentation. The program's objective reports can spur the investigator to further discuss topics the viewer did not completely understand. In essence, the investigator's educational efforts become streamlined and refocused. If the viewer missed exam questions, the investigator reviews the correct answers with the parent or child. If sections of the presentation were watched more than once, further discussion may be warranted to ensure understanding. If the viewer utilized the question button to type out a question, the investigator can provide further education relating to the topic. In essence, technology can deliver a baseline understanding and promote a more subject-specific discussion between the investigator, parent, and child.
Accurate feedback also allows sponsors to compare enrollment and retention data in real-time. Adjustments can then be made at the site level to maximize recruitment success.
Development costs for multimedia content vary by vendor, project size, and project medium. Sponsors or research teams can expect to spend tens to hundreds of thousands of dollars for most custom-made presentations. For most studies, however, the total expense ends up being less than $1000 per patient enrolled with return on investment commonly reaching 30%.
Sponsors often find production costs to be negligible in light of the increased recruitment rates and decreased study duration they experience when using interactive informed consent.
Once content is created, there are production and distribution costs to consider for each potential platform. Distribution costs include both the recording of the content (if CD-ROMs, DVDs, or videotapes are used) along with the postage costs of shipping it to the research sites. Content for clinical trial Web sites or customized software packages can be distributed fairly inexpensively. The expense for initial distribution and any updates is often included in the producer's monthly pricing structure. Similar to electronic data collection (EDC) technologies, there are study set-up fees, ongoing study fees, and study closeout fees. The costs within each of these categories include software licensing, training, and support. The technology's cost varies depending on several study parameters, including the number of patients, sites, and months in the study. The amount and type of content created will also influence the costs.
An attractive cost benefit of customized software and Internet content is its value in future clinical trials. Many times, content developed in a Phase I or II study can be re-used in a similar Phase III or Phase IV study without any additional costs.
The current informed consent dyad of pediatric trials poses a significant challenge to sponsors and researchers. The parent must decide to allow the child to participate in research, and the child must grant his or her assent. It is widely known that pediatric subjects are not simply "little adults," and their education about a trial's risks, potential benefits, and requirements must reflect this core principal. Many educational institutions recognize the advantages of multimedia education—seen especially with children—and are aligning technology with traditional teaching methods. If the clinical trials industry is to benefit from technology-based informed consent education, manufacturers and researchers alike must push for this change.
Sponsors, researchers, and subjects of clinical trials all stand to receive considerable benefit from an improved consent process. Interactive technologies aim to effect this change. Research sites must deliver high-quality content through a platform that allows maximum interactivity, flexibility, and feedback. By improving the pre-trial education of adult caregivers through new technologies, this group will have a better understanding of the proposed clinical trial. This improved understanding can assuage the concerns of anxious parents, likely promoting a greater willingness to permit their child's participation in the trial. Given the ease with which the current cadre of pediatric subjects utilizes technology, it is clear that multimedia education can help researchers meet these subjects on a common ground—clearing the way for better understanding and willingness to grant their assent.
As multimedia consent continues to become more popular in clinical trials, the industry will see a major impact on subjects' satisfaction and understanding. Equally important, a faster recruitment process will emerge—benefiting drug, medical device, and biotechnology producers and consumers alike. Trial timelines will shrink, direct costs will drop, and potential revenue will increase.
While pediatric subjects may continue to use the latest electronic advances primarily for their own entertainment, it appears technology can be used for more than just fun and games after all.
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