In response to the request for opinions in connection with the use of placebo in clinical research (

, August 2004, p. 12), we wish to propose a method of individualized analysis (case by case) of research protocols. This method is mainly based on the assumable risk for patients from the different study groups (experimental and comparison or control groups).

From a methodological point of view, the comparison with placebo in the initial development phases of drugs (before initiating comparative studies with standard treatment) would allow the evaluation of the efficiency of a new molecule in a smaller number of patients. In this way, their exposure to possible toxic or inefficient treatment is minimized, costs are reduced, and the introduction onto the market of inefficient medicines is avoided. Moreover, it would detect situations of a high response to placebo-due to the undulating course or spontaneous remission of the disease.

From the ethical point of view, it must be taken into account that a protocol that is not scientifically correct is ethically unacceptable, although the reverse is not always true. Even if it is necessary to use placebo for scientific reasons, it may not be ethically justified. We believe the ethical considerations that must be considered are as follows: The use of placebo must not involve the deception of patients (placebo is not a treatment); replacing active treatment with placebo may cause the disease to worsen (when placebo is used as a comparative); on occasion it may cause damage directly (i.e., according to the composition of the placebo), or indirectly from the deprivation of a treatment validated during pre-inclusion, washing, or withdrawal periods.

In this last case, two possible situations must be distinguished: one, when there is no accepted standard treatment, and two, when accepted standard treatment is available. The acceptance of the use of placebo in this second case implies the assessment of the possible significant damage (the risk of death or serious irreversible damage). This posture corresponds to the so-called orthodoxy of the placebo. In the opposite case this would be unacceptable as a proven treatment exists (orthodoxy of active treatment).

In our opinion, an IRB, in order to report favorably on a research protocol that includes a placebo group, must check that the following requirements are being complied with:

1) Methodological reasons exist and it has been concluded that the probability of damage or lesions is similar for the patients of the placebo group and those of the experimental group (as to mortality, irreversible morbidity, disability, or other significant damage, albeit reversible, or significant discomfort). 

2) Additional measures necessary for lessening the probabilities and/or minimizing possible damage to subjects have been taken. For example, excluding high-risk patients (damage or lack of response), limiting the duration of the period with placebo, carefully monitoring patients (those in hospital, means of rescue, etc.) and establishing explicit withdrawal criteria.

3) The obtaining of informed consent is anticipated, after informing in a full and understandable manner on the use of placebo, the reasons for this, and the possible risks.

4) Finally, optimum treatment must be offered to each subject after the study has ended.

To sum up, in our opinion it is not possible to be totally in favor of or totally against the use of placebo in clinical research. Assessment and deliberation by a committee of experts should be carried out before a decision is made as to whether a specific protocol is "ethical" or not. In this way, it could be concluded that it might NOT be ethical if efficient treatment of vital importance exists and if the patients assigned to the placebo group are more likely to suffer damage, or greater damage than those allocated to the treatment group. And on the contrary, it could be ethical in slight or lesser pathologies, in the absence of proven treatment, when there is a minimal probability of patients assigned to the placebo group suffering damage or lesions (when the risk does not exceed the minimum).


del Castillo, MD, PhD
Clinical Pharmacologist


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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.

 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.

 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 

 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.

 It is unsurprising, then, that 14% of potential subjects do not even read—or attempt to read—the informed consent document.

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.

 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: 

increases knowledge scores by up to 40% more than traditional written instruction

improves subjects' adherence to protocol by up to 31%

increases realistic expectations twice as much as traditional education methods

decreases anxiety twice as much as written informed consent and discussion with the provider

instills a sense of control in subjects, as they feel they can dictate the pace of their learning

is preferred over similar face-to-face healthcare encounters

nearly doubles recruitment rates for clinical trials.

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: 

the ability to provide feedback to the subject and investigator

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. (

). 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.  

1. U.S. Department of Education. The Secretary's Conference on Educational Technology: Evaluating the Effectiveness of Educational Technology [Online] (July 1999), available: 

www.ed.gov/rschstat/eval/tech/techconf99/confsum.html.

2. V. A. Mathie, "From Blackboard to Multimedia Classroom," 

3. H.J. Bailey and N.E. Thornton, "Interactive Video: Innovative Episodes for Enhancing Education," 

Computer Applications in Engineering Education

4.  M. Paasche-Orlow, H.A. Taylor, F.L. Brancati, "Readability Standards for Informed-Consent Forms as Compared with Actual Readability," 

5.  M.V. Williams, "Recognizing and Overcoming Inadequate Health Literacy, a Barrier to Care," 

6. Editorial, "Inside the Informed Consent Process" 

7. R. Yuval, D. Halon, A. Merdler, N. Khader, B. Karkabi, K. Uziel, B. Lewis, "Patient Comprehension and Reaction to Participating in a Double-Blind Randomized Clinical Trial (ISIS-4) in Acute Myocardial Infarction," 

8. J. S. Brady, "Multimedia Delivery Can Enhance the Consent Process," 

9. Jeffrey S. Brady, "A Better Way to Get Consent," 

10. S. Krishna, E.A. Balas, D.C. Spencer, J.Z. Griffin, S.A. Boren, "Clinical Trials of Interactive Computerized Patient Education: Implications for Family Practice," 

11. K. Huss, M. Salerno, R. W. Huss, "Computer-Assisted Reinforcement of Instruction: Effects on Adherence in Adult Atopic Asthmatics," 

12. A. Rostom, A. O'Connor, P. Tugwell, G. Wells, "A Randomized Trial of a Computerized Versus an Audio-Booklet Decision Aid for Women Considering Post-Menopausal Hormone Replacement Therapy," 

13. C.T. Cowl, B.T. Petersen, G. Smith, S.C. Hauser, "Evaluating the Use of Computer-Based Interactive Technology for Improving Outpatient Procedure Education," Presented at the American Medical Informatics Association Symposium in San Antonio, TX, November 12, 2002. 

Feature Article

To ensure that everyone involved recruiting pediatric subjects is on the same page, maybe it's time to go to the videotape.

More Than Just Fun and Games?

A skillful mix of marketing and management savvy together with scientific expertise makes a recruitment campaign sing.

Effective subject recruitment is a cornerstone of clinical research. In 2001, over 85 percent of all completed medical research studies experienced enrollment delays, and 34 percent were delayed for more than one month.

 Such postponements can cost pharmaceutical companies millions of dollars in missed sales. For example, according to The Pharmaceutical R&D Compendium, delays in getting a drug to market in 2000 were estimated to cost companies around $1 million per day.

 In 2003, a month-long delay cost sponsors an estimated 

 Because of these realities, developing effective subject recruitment programs has become even more critical to the industry. With less than 10 percent of eligible patients participating in clinical trials at any time, subject recruitment programs can increase a sponsor's capability to reach those who have never considered participating in clinical research.

Effectively raising awareness of the need for clinical research subjects must be handled methodically and with integrity. To understand what makes a subject recruitment campaign successful, one can view the procedure as a five-step process that includes subject profiling, market segmentation, marketing communications planning, centralized pre-screening, and trial management. All of these steps are integrated and interdependent, and effective subject recruitment can only happen when all of these elements work together.

The following case study will illustrate how all of these fundamental aspects come together to create an effective subject recruitment campaign. A cost-effective campaign to recruit qualified participants for two separate clinical research studies was to be executed for Pharmacia. Both studies focused on the treatment of a socially sensitive pediatric condition. The overall recruitment goal of the multimonth study required identification of 225 qualified subjects across 32 sites throughout the United States.

Here is an overview of the five-step process and how it was implemented for these studies:


Subject profiling includes understanding the subject population; utilizing demographic, psychographic, and statistical research sources; and consulting with medical professionals. Both clinical expertise and marketing expertise are required to describe the target population for a recruitment campaign. Just as every indication is different, every protocol is different. Various exclusion and inclusion criteria create a distinct subject profile for every study. After developing a subject profile, source mapping and recruitment planning can be done to determine which outreach programs will be the most effective in identifying subjects.

With some indications, potential subjects are not in control of their own healthcare decisions, and their caregivers are the targets of the awareness campaign. For example, in clinical research studies regarding pediatric or elderly conditions, a parent or caregiver is most likely to be the one making the health care decisions for the subject. In such instances, both subject and decision-maker profiling are crucial in creating an effective campaign.

For profiling in the pediatric studies, target populations had to be examined on a variety of levels. Since the subjects sought were children, the caregivers were the decision-makers and the target audience for the recruitment message, due to their responsibility for making the healthcare decisions for the study candidates. For profiling purposes, it was critical to determine who these caregivers were. The research revealed that women between the ages of 25 and 49 are most likely to have children ages 5 to 10 years old, and that women are typically the healthcare decision-makers. Thus, the person targeted was a young woman with a young child. This profile allowed for investigation into the sites where the study was going to be conducted, in order to determine the designated market areas with the greatest incidences of both the target audience and the subject population.


Market segmentation involves researching the optimal locations to find qualified subjects. Markets are ranked to pinpoint where the highest concentrations of potential subjects are. There are many variables used in this analysis, including population counts, incidences of target demographic households, and the prevalence of the disease in the market.

From the beginning, the protocol must be analyzed not just from a clinical standpoint, but also from a demographic perspective. This includes evaluating the target subject population, determining the incidence of the condition based on geographic location, establishing site qualifications, and confirming subject accrual timetables and rates based on prior studies.

The values and norms of the target audience must be known intrinsically: What factors influence individuals to enter themselves or someone in their care into a clinical research study and what elements make them shy away from it? What are their priorities? Where do they get their information? When do they consider participation in clinical research a viable option? This information aids us in finding the target audience in specific locations and determining the best methods to reach them.

In the pediatric campaigns, a national database was used to uncover demographic information, media usage, audience psychographic information, product usage, and media consumption. The research provided knowledge about the media use habits of adult women with children between the ages of 5 and 10 years old, since, as previously discussed, these women were making the health care decisions for their children. We learned that our target audience obtained information through personalized sources, such as direct mail and communication with their pediatrician.

Markets with higher populations of children were also identified, since a greater population of children indicated not only the presence of more potential subjects, but of more mothers who might be receptive to the recruitment message. Some markets were more successful in their recruitment efforts than others, simply because some areas had a higher potential subject population. For example, the Jackson Hole, Wyoming site had a very small population of women with children within a 60-mile radius, so subject recruitment was a challenge. The Louisville, Kentucky site reached its recruitment goal very quickly because of the high population of women with children in the market.


Once the target audience is described and more is known about its media consumption habits, the best way to reach the subject or decision-maker profiled in the identified market segment is determined. Various tactics are taken into consideration, including newspaper, television, and radio advertising; Internet banner ads; direct mail; brochures; posters; investigator education materials; and public relations services.

As specific tactics are implemented, creativity becomes a large part of the process. Because of today's hectic lifestyle, a creative message is imperative to attract attention and gain awareness. Direct messages are formulated and customized to the target audience. Materials are designed and produced. Public relations activities can be conducted to show the positive impact of medical studies and to educate the public about the condition, as well as to attract potential subjects. Direct marketing and media advertising plans are implemented. All recruitment and advertising materials and initiatives must be IRB-approved prior to implementation to ensure that the materials accurately portray the study. The role of the IRB is to protect the interests of potential subjects.

Creativity plays a critical role in attracting the right individuals. Each study requires different tactics, depending on how the target audience receives their information. The goal is always to attract, inform, and retain eligible subjects. Research indicates that higher response rates are received by advertising that has a consistent look, that reinforces the recruitment campaign message, and that is strategically placed through effective media buying.

Formulating the message for the pediatric studies was a challenge because of the sensitive nature of the condition. The focus of the recruitment message was a reflection of the thoughts and emotions felt by someone impacted by this condition.

Tactics included print advertising, primarily in parenting magazines; two direct mail campaigns, one to pediatricians within 20 miles of each site and one to households near each site; Web site development; and public relations. Only households with children ages 5 to 10 were targeted.

In the interest of raising consumer awareness of clinical trials, the Web site that was run in accordance with this study included some general questions and answers on medical research studies. An informed individual is more likely to be interested in a study, and is also more likely to follow the study regimen, take an active part in their care throughout the study, and remain enrolled for the duration of the study.


Centralized prescreening means that there is one centralized location for all information regarding potential participants. The goal is to ensure that only the most qualified potential trial participants are scheduled with various research sites. The centralized procedure facilitates accurate tracking and analysis of recruitment activity as it occurs.

Systems such as interactive voice response (IVR) streamline the subject screening process. IVRs are utilized to prescreen candidates and to collect data throughout the study. Call centers with toll-free numbers collect subject information at a central source, and the IRB-approved prequalifying questionnaires can be used to prescreen individuals. Customized Web sites are now being used to post the prequalifying questionnaire and to pre-screen candidates online through a secure network setup.

The comprehensive Web site for the pediatric studies served two purposes: first, to inform and educate the public about the studies; and second, to prequalify potential trial participants. Because individuals are often reluctant to submit personal information over the Internet, Secure Socket Layer technology was used to ensure the security of the information presented online through the prequalifying questionnaire. The prequalifying questionnaire incorporated the inclusion/exclusion criteria to screen subjects for the studies. In this manner, individuals could be automatically qualified or disqualified from the candidate pool. Fifty-four percent of all prequalifying questionnaires were completed on the Web site, the balance via telephone.

In accordance with HIPAA and IRB regulations, it is imperative to respect the privacy of potential subjects and their medical information. In the pediatric studies, whether the inquiry came via telephone or the Web site, all inquiring individuals were asked to grant permission to collect information before completing the prequalifying questionnaire. When subjects prequalified, they were instructed that, with permission, their information would be sent on to a research site. For those who did not qualify, or did not wish to have their information sent on, the information was destroyed.


The trial needs to be managed once the subjects are recruited, have qualified for the study, and have given their consent to participate. Hands-on subject support and personal attention must be implemented. Study coordinators need to stay energized and motivated, and principal investigators must stay well-informed and subject-focused.

Indeed, to ensure subject retention, the focus should remain on the subject throughout the trial. Nearly 40 percent of all prequalified volunteers fail to enroll due to inconvenience and lack of responsiveness from investigative site personnel. In an analysis of more than 1,700 prequalified study volunteers for Phase II and Phase III projects, CenterWatch found that 13 percent never enrolled because there was no conveniently located investigative site, 14 percent of prequalified subjects lost interest following their initial interactions with call center or study staff, and 23 percent of prequalified volunteers were never randomized because no one contacted them after the initial phone screen.

The success of a clinical research study involving a lengthy time commitment by the subject depends greatly on the perceived value of the care the subject is receiving. Careful consideration should be given to reimbursement methodology and retention strategies. It is important that the study participant understand the commitment and responsibilities required for participation in a clinical research study. Reimbursement and retention strategies must be more frequent, creative, and varied when an extended time commitment is involved.

Every subject who enters into a clinical trial is valuable. There are many reasons why eligible subjects refuse to enter a study, or drop out once they have enrolled. Some of these reasons include: misperceptions about clinical trials in general, concerns over the protocol, perceived complexity of the protocol, poor motivation to continue, and lack of support and guidance during the study.

Subjects who adhere to a study regimen are those who are informed about the study and the condition. They have regimen aids and support for transportation arrangements. They also have a commitment enhanced by a sense of community within the study, and they receive appreciation items throughout the study.

Study coordinators and principal investigators (PIs) also need proper training. Not only does the investigator meeting need to present the inclusion and exclusion criteria and specifics about adverse event reporting, but the PI also needs to address how to treat study participants as valued customers rather than merely research subjects. Site staff need to know what materials are going to be available for recruitment, as well as the goals, objectives, timeframes, and projected milestones for the study.

Subject retention is the key to the clinical trial process. Subjects want and deserve personal attention from everyone they are in contact with at the site. Retention tools such as newsletters, reminder postcards for appointments, appreciation items delivered throughout the study, and follow-up phone calls are essential in making individuals feel like they are an integral part of the study. These communication tools can also educate participants about their condition.

Subjects will also want their questions answered: What are the side effects of the medication? How many office visits will I have to make? Is there a stipend for participating in the study? What about transportation and childcare? Study site staff members need to be properly trained to answer these questions and to make follow-up calls with subjects. Site staff should receive a list of frequently asked questions and designated responses.

Web-based information systems are now being developed to assist research sites and pharmaceutical companies in subject recruitment and tracking analysis. These systems facilitate a single tracking log for all subjects and potential subjects. Clinical research site staff, pharmaceutical company sponsors, and clinical research organizations utilize one system with a specific username and password. This identification system determines which study data may be accessed and at what level of access. The subject log can be retrieved and updated by clinical research site staff. Sites benefit from this arrangement because they can immediately update candidate information on one simple electronic form as changes occur in the candidate's status. Once a candidate prequalifies, the subject's information can automatically be added to the system and updated throughout the study. Site staff can also retrieve graphs pertaining to enrollment and candidate outcomes for their site. As subject information is updated, site staff, sponsors, and clinical research organizations can have constant, real-time access to an analysis of the recruitment plan using secure HIPAA-compliant platforms.

Flexibility is key in effective subject recruitment. In the pediatric studies, sites that offered early morning, evening, and Saturday hours for appointments were more successful in their subject retention efforts. It is important to make it easy for subjects to stay with the study program.


The program is evaluated throughout the process to determine any necessary adjustments and to monitor responses. Following the culmination of the recruitment period, a comprehensive review is done to determine the success of the campaign and the specific tactics, such as advertising, direct mail, public relations, and referrals from doctors or friends. A comprehensive report is issued to communicate the results.

The recruitment goals were exceeded for the two pediatric studies. Exactly 435 prequalifying questionnaires were completed and 256 children successfully prequalified for participation. Evaluation of each referral source vividly illustrates how the integrated communications approach effectively met the goals of the recruitment effort. Qualified candidates were referred to the studies from all recruitment tactics implemented.

Public relations initiatives netted newspaper placements; talk radio interviews; segments with local ABC, NBC, and CBS affiliates; and post-air story placements on station Web sites. Conveying the recruitment campaign in a news-type format enhanced the credibility of the message, because of the value the public places on news stories. The news stories focused on the condition and the study was mentioned as a sidebar.

Subject recruitment is a process that relies on the integration of subject profiling, market segmentation, market communications planning, centralized prescreening, and trial management. A puzzle is not complete without all of its pieces, and subject recruitment campaigns can only be as effective as the sites supporting them.

Treating the potential subjects with the respect and courtesy that they deserve, and giving them the information to make informed decisions, is integral to successfully recruiting an interested and cooperative pool of subjects. 

Also, it is imperative to realize that subject recruitment is an intricate process requiring marketing and management expertise together with the scientific expertise. Experience and research are required to analyze the protocol, to find optimal site locations, and to understand the demographics surrounding the media habits of the target subject population. Tying it all together creates a cost-effective recruitment and retention program for each study.

Experts in these fields should be engaged to take on these campaigns and are available through centralized subject recruitment and retention companies. These firms are skilled in incorporating the local level experience of the study coordinators and doctors with marketing research, media planning, and a creative message that allows them to prepare, execute, and manage a successful recruitment program.


1. V. Gamache, "Minimizing Volunteer Dropout," 

 1, 9-12 (December 2002).
2. F. Kermani and G. Findlay, The Pharmaceutical R&D Compendium (2000); available at www.cmr.org/publications/books.html.
3. S. Space, "Site Strategies to Improve Recruitment Advertising Effectiveness," 

 1, 9-13 (October 2003).
4. K. Koreith, "Taking Patient Recruitment In-House," 

 1, 5-9 (February 2004).
5. B.D. Harper and L.-O. Eriksson, "One Size Does Not Fit All," 

 42-48 (November 2002).
6. F. Kilpatrick, "Rev Up Patient Recruitment," 

 (April 1, 2002).
7. S. Space, "Site Strategies to Improve Recruitment Advertising Effectiveness," 

 1, 9-13 (October 2003).
8. A. Neuer, "Treating Study Volunteers as Customers," 

Donna Beasley is vice president of operations with Praxis, 5141 Virginia Way, Suite 450, Brentwood, TN 37027, (615) 312-8207, fax (615) 312-8208, email: info@gopraxis.com.		

Perfect Harmony

If an investigative site is to grow successfully, specific functions of the clinical trials process must first be solidly in place. A common pitfall in this industry is for the owner or Director of Business Development of a young site to promote itself before it can adequately perform more studies. This happens when site management has not yet recognized the critical importance of developing the appropriate infrastructure needed to support a site aiming to grow its clinical trials business carefully and thoughtfully. There are basic elements (Figure 1) needed to build a firm foundation for growth with quality, and while a detailed discussion of each of these functions is beyond the scope of this article, a few are highlighted. 

The Director of Clinical Operations (DCO) is crucial to site growth and, assuming the right person is hired, will be instrumental in moving the site to the next level. The DCO oversees all of the day-to-day clinical operations. He or she meets weekly with all study coordinators; assigns studies to the study coordinators based on their experience and current workload; participates in all study initiations, close-out meetings, monitor visits, Food and Drug Administration (FDA) and sponsor audits; meets with the quality assurance team to discuss trends and issues; acts as a liaison between the sponsor, investigator, and study coordinator to address issues relating to protocol compliance; oversees formal staff training on many topics, including HIPAA; and is involved in any clinically-related issue with regard to budgeting, contracting, and salary reviews. The DCO is the glue that holds the site together. All study coordinators, research assistants, regulatory staff, and laboratory personnel report to the DCO, who in turn, reports directly to the primary investigator and the CEO. 			

The ideal candidate is someone who has had site experience, is familiar with good clinical practice standards, and has a clinical background, such as a nurse who has worked in an ICU or in some other type of nursing environment with rigid, military-like rules and constraints. Hiring someone with this kind of background will increase the likelihood that the individual can function in a highly structured, regulated workplace. The DCO should also have management and leadership skills. Previous experience as a monitor is desirable, but it is strongly preferred that the DCO have site experience as a study coordinator, or as some other site-based clinical professional (see sidebar "If You Need an Apple, Get an Apple").   

Figure 1.  Key Elements for a Successful Site			

The growing site needs to establish a quality assurance (QA) department, even if that department starts with nothing more than a single full-time equivalent (FTE), or a partial FTE, depending upon workload. A number of site alliances and site management organizations (SMOs) share one quality assurance FTE who travels from site to site, to QA the charts prior to monitor visits. Sponsors, CROs, and monitors recognize and appreciate this investment in quality. 			

The purpose of the QA department is to develop and implement programs designed to improve the quality of studies conducted at the site,

 starting from day one. This raises the bar for patient safety, and should enhance outcomes of monitoring visits.    

Figure 2.    Key Responsibilities of the Quality Assurance Department.			

The QA function is a standard business practice for overseeing product quality (Figure 2). Quality Assurance, as defined by the International Organization for Standardization (ISO 9000), refers to a set of activities whose purpose is to demonstrate that an entity meets all quality requirements. QA activities are carried out to inspire the confidence of both customers and managers that all quality requirements are being met.

Applying this definition to the clinical trials industry, QA serves to ensure that Good Clinical Practice (GCP) guidelines are adhered to, resulting in a quality product: clean, reliable data. According to FDA, GCP is a standard for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical trials.

 Compliance with this standard provides public assurance that the rights, safety, and well being of trials subjects are protected, consistent with the principles originating with the Declaration of Helsinki; and that the clinical trial data are credible.

 Helpful Hints to Improve Site Performance and Outcome at Audits.			

Because of its importance, the QA team should report to the highest level of management, and maintain independence from the operations group.

 In addition, the QA team should be presented to the site as a positive, cooperative force, and not as adversarial to site operations.

 Using this approach, the QA team can audit studies at prescribed times, such as at study-up, and once a month thereafter. Findings of each audit are to be shared with the principal investigator, sub-investigators, study coordinators, and any other personnel involved with the study.  The auditing exercise can serve to prepare the site for monitoring visits, FDA audits, and sponsor audits.   

To facilitate the operation of a GCP-compliant site, a good Quality Assurance department works with all levels of management to develop standard operating procedures (SOPs). These procedures are designed to bring consistency to common practices conducted at the site by providing a standard format, method, authorization trail, and implementation process. The goal of SOPs is to improve quality by preventing or limiting errors and non-compliance problems at the site level. The QA Department should review the SOPs annually to keep them current, and should be diligent about their being followed. 

SOPs address a wide range of clinical and administrative topics, ranging from obtaining informed consent to randomization procedures to collecting data to handling a code on a patient (Figure 3). Most procedural errors occur with the first three or four patients enrolled in a study, so it is a good idea to develop an SOP instructing the QA Department to review and approve all charts and source documents for the first four patients in all studies. Once enrollment extends beyond the first few patients, it is suggested to have all paperwork completed by the study coordinator, research assistant, or data entry staff within 24 hours of each patient visit. This process limits the number of missed procedures. For example, the study coordinator may have taken a blood pressure reading during the patient visit, and may have quickly jotted it down on a piece of paper instead of recording it in the case report form. Implementing this simple procedure can improve the quality of the paperwork completed at the site.       

Whether sites create their own SOPs, or customize templated SOPs, they include various elements such as title and objective (Figure 4). As company SOPs are generally considered to be confidential documents, it is recommended that anyone at the site who is given the SOP binder fill out a sign-out sign-in sheet to document this transaction. If SOPs appear on the company's intranet, they should be password-protected. Further information about SOPs can be found in 

Figure 4. Sample Format for Standard Operating Procedures (SOPs).			

Growth at the site level is accompanied by a tremendous increase in regulatory paperwork generated in support of clinical studies. This workload becomes particularly noticeable once the site reaches a milestone of some seven to nine ongoing trials. As long as the site participates in a smaller number of trials, it is usually possible for regulatory responsibilities to be assumed by an administrative type or by the study coordinator. Once this milestone is reached, however, the site will probably need to hire a regulatory affairs person.   			

Initially, this individual may assume other administrative duties if he or she is not fully consumed with regulatory paperwork, but eventually the position will expand into a full time job. Some of the responsibilities of the regulatory affairs person (or, eventually, the regulatory affairs director) include corresponding with local, central, and in-hospital Institutional Review Boards (IRBs); keeping abreast of HIPAA issues; maintaining all paperwork for the regulatory binder; and properly reporting adverse events (AEs) and serious adverse events (SAEs) (Figure 5).   

Figure 5. Some of the Tasks Assumed by Regulatory Affairs.			

Dedicating an FTE to regulatory activities will accomplish two major goals: it will free up the study coordinator to perform other study-related tasks; and it will improve the site's turnaround time for submitting paperwork needed for study startup. Offering good turnaround times is an important marketing tool for the site. It shows efficiency, and complements the skill, knowledge and experience that a site can offer to sponsors.   

The regulatory binder is the record of study documentation. Because all clinical studies tend to have many of the same components, the regulatory affairs department, with input from the site, should consider developing a format for the binder that standardizes needed documents for all studies. Although various sponsors and CROs may provide study binders, it is preferable that the site uses its own standard binder. This will regiment the site, and enhance quality by organizing paperwork needed for proper study conduct and for visits from monitors, FDA and sponsors. 						

IRB-approved signed informed consent forms 

 Continuing and final review reports (CVs and medical licenses of the principal investigator(s) and sub-investigator(s))

 Letters of indemnification and confidentiality  

 21 CFR (Code of Federal Regulations) 54 Financial Disclosure by Clinical Investigators

 Clinical supplies: Proof of receipt of CRFs, lab kits, diaries, etc. 

 Protocols, protocol amendments and signature pages

 IRB-approved materials, IRB correspondence and Continuing Review Reports

 General correspondence with the CRO and/or sponsor (includes newsletters)

 Site signature and delegation logs (stating who is responsible for which study activity.  The logs are signed and initialed).

 Screening logs (documenting who was screened for enrollment)

The real test of a site's preparedness is how it fares during an audit by FDA. It's not a question of if an FDA audit will happen, but when. According to the Center for Drug Evaluation and Research (CDER), a division of FDA, there are approximately 300 onsite inspections annually of U.S. clinical investigators (Figure 6). Inspections can last anywhere from several days for routine inspections to a few weeks if serious problems are uncovered. 

Because of its importance, the QA team should report to the highest level of management and maintain independence.

QA for the Investigative Site

The pharma industry won't be the only group rewarded for conducting new pediatric research.


Olli Rehn is not a name well-known across Europe or the rest of the world, but the children of Europe may well have reason to look back with satisfaction when they are adults on the brief encounter this obscure Finn had with European pharmaceutical affairs.

Rehn has recently been projected into prominence as a member of the European Commission, the select group of senior officials who direct European Union business. As of November he will be in charge of enlarging the EU to take on Bulgaria, Romania, Croatia, Turkey, and other countries to the south and east.

At the end of September, however, it was his role as commissioner of industry to announce a new approach to develop medicines for children. After years of reflection, the commission finally came up with its plan for promoting trials in pediatric medicines. 

Most of the lengthy preparatory work took place under the aegis of compatriot Erkki Liikanen, the industry commissioner predecessor. But since Liikanen was prematurely called away from Brussels in September to take over as President of the Finnish Central Bank, Rehn was suddenly promoted to step in for him. So Rehn will take the credit-or blame-for how the scheme works. 

The proposal aims to address a well-recognized public health problem: more than half the medicines used by children in the EU have not been tested or authorized for their use. As Rehn expressed it, "Our children are denied innovation and they may even be given ineffective or harmful treatment." Market forces are insufficient to supply the medicines children need, he said. So the EU has tried to strike the right balance between meeting public health objectives and strengthening the competitiveness of the pharmaceutical industry.

Since December 2000 the European Commission has been searching for the best solution, including studying U.S. experience and assessing the effectiveness of the European regulation on orphan medicines. It has been juggling how to promote the development and authorization of pediatric medicines without any unnecessary studies in children, and without delaying the authorization of medicines for adults.

For a medicine still under patent, a new requirement will be to present results of studies in children conducted according to an agreed plan, at the time of application for marketing authorization. This requirement will also apply when companies apply to extend the use of the product, for example by using it at a different strength. However, this will be waived for medicines developed for adults that are not useful for children. In addition, it may be safer to study some medicines in children only after studies have been conducted in adults. In this situation, there will be a deferral starting or finishing studies in children.

The Commission believes the pharmaceutical industry be rewarded for conducting the additional studies, so a six-month extension of the supplementary protection certificate will be granted-in effect an EU-wide patent extension.

For orphan medicines, the situation is different. Not all orphan medicines are patented, and they already get 10 years of market exclusivity. So orphans will receive an additional two years of market exclusivity in addition to the 10 they already have.

The situation is admittedly more difficult to fix for off-patent medicines, because such products have often been on the market for many years via multiple license-holders, including generic companies. They have no intellectual property rights, and yet they may be of great therapeutic value to children. So the proposed solution is that new off-patent medicines specifically developed for children should be granted a new type of marketing authorization-the Pediatric Use Marketing Authorisation, or PUMA. Newly developed but off-patent products can be granted 10 years of data protection on any newly conducted studies. In addition, the PUMA allows the use of the existing brand name, which is of obvious commercial interest to the industry.

In terms of data requirements, the PUMA will, for the first time, allow a generic-type application to be combined with the new studies in children. This should make it easier for industry to develop these medicines.


There will also be measures applying to all medicines, on- or off-patent. One will be the establishment at the European Medicines Agency of a new expert pediatric committee to scrutinize companies plans for testing medicines in children. This will be designed to ensure research is of high quality and only conducted when it will benefit children. In addition, a European network of investigators and trial centers with expertise in children's medicines will be set up to help the conduct of studies in children. The European Medicines Agency will also provide-free of charge-scientific advice on how to conduct studies in children.

To ensure high-quality information about the safe and effective use of medicines, an inventory will be established of the therapeutic needs of the children of Europe to help identify where products are needed. New product labelling requirements will ensure children, parents, and doctors can make informed decisions about treatment. And a database of studies in children will be set up to ensure studies are not duplicated, and so the results of studies are put to best use. Industry will be required to submit to the authorities study reports they already hold on use of their medicines in children, to maximize the utility of existing data and knowledge.


There will also be enhanced safety monitoring for marketed products, to ensure that the newly developed products are closely followed once they are on the market.Part of the proposal also foresees a separate initiative to create an EU pediatric study program called Medicines Investigation for the Children of Europe (MICE), to fund research leading to the development and authorization of off-patent medicine for children. 

The proposal immediately won support from European drug industry organizations. The European Federation of Pharmaceutical Industries and Associations welcomed it as an important step. "Overall, we must work towards an ethical, effective, and favorable environment in Europe for pediatric research and development of specific medicines to treat diseases in children. The adoption of a EU legislative framework is an opportunity to improve public health and strengthen Europe's science base," said Brian Ager, director general of EFPIA. "Industry, regulators, patient groups, doctors, pediatric societies and EU researchers all have a role to play. The goal is to foster pediatric research in Europe for medicines adapted to the needs of Europe's children." EFPIA said it would continue to work for appropriate regulatory and incentive measures to be put in place to stimulate pediatric research and development in Europe and fast access to innovative medicines for patients of all ages.

The Association of the European Self-medication Industry, representing manufacturers of nonprescription medicines in Europe, welcomed the proposal. "The Commission has chosen a reasonable approach in the area of non-prescription medicines, encouraging relevant research without forcing unnecessary studies," declared AESGP's Director, Dr. Hubertus Cranz. "Although some details may need clarification, the proposal is going in the right direction."

The proposal will now start its progress through the EU's legislative machinery, with examinations by the European Parliament and national ministers in the EU Council. The earliest that the proposal is likely to become law is late 2006. Olli Rehn will by then be enmeshed in the intricacies of EU accession negotiations with Turkey and the countries of the western Balkans. But children being born today may stand to benefit throughout their lives-for themselves and for their own children's children.

Sidebar: The Reasoning Behind the Rewards


The European Commission has been hard-headed in its assessment of what will be needed to make a new system work. It has set out the arguments explicitly in documents accompanying the proposal. In summary, its reasoning for providing rewards is as follows:

Applied Clinical Trials-11-01-2004

Letters to the Editor

More Than Just Fun and Games?

Perfect Harmony

QA for the Investigative Site

Pediatric Trials: A New Approach Is Born

Medical Law and Research

Safety Problems Challenge Clinical Trial Design