OR WAIT null SECS
How text messaging could revolutionize clinical trial subject recruitment and compliance.
Subject noncompliance in clinical trials ranges from 20% to 80%, depending on the therapeutic area. This is due to a number of factors, including subjects failing to follow medication regimes, missing clinical visits, and failing to comply with crucial requirements of the study. Replacing noncompliant subjects can have a significant impact on cost, recruitment, timelines, and the data quality of a clinical study. As a result, overcoming subject noncompliance is an increasingly important issue in the pharmaceutical industry.
(Photography: Jim Shive)
It is possible to minimize subject noncompliance through a number of methods, including targeted subject recruitment, the use of electronic diaries during a study, and communicating reminders directly to subjects. These methods are increasingly complemented by the adoption of new technologies such as Short Message Services (SMS)—or text messaging as it is commonly known.
There are currently an estimated 3.3 billion cell phone users worldwide,1 surpassing the number of home Internet users by 2 billion. And there are now more cell phones than people across much of Western Europe. Text messaging technology is a solution already used in the consumer sector with immense success, and it is now developing into a workable solution for the clinical trials arena.
By using SMS communication to interact directly with subjects, pharmaceutical sponsors can improve subject recruitment, retention, and compliance in a cost-effective way that is also personal and confidential for the subject. This article will discuss current strategies for doing this, the integration of SMS technology into existing processes, regulatory challenges, and the future of communication technology in clinical trials.
Finding quality volunteers and subjects for a clinical study can be extremely challenging and directly affects the success of an entire clinical program. Although physician referral has traditionally been a common form of subject recruitment for clinical trials, advertising is fast becoming the most effective method. Studies have shown that while 44% of subjects find out about trials through the media, only 14% gain the information from their physicians.2 Depending on regulatory restrictions, sponsors can advertise for subjects in a wide range of environments, including hospitals, clinics, and universities, as well as on television, radio, and in the cinema.
SMS technology can easily be used by sponsors to communicate with and elicit responses from subjects during a trial.
Subject recruitment advertisements need to include a strong call to action—for example, a Web site address or telephone number where potential subjects can find out more information about the trial. This project is usually undertaken by an external call center, where outsourced staff can field questions about the trial and take people through a series of questions to determine suitability for a trial.
New technology can complement the subject recruitment process. For example, Web-based questionnaires and interactive voice response technology can filter out unsuitable individuals. However, these methods all require the potential subject to take the first step, meaning that many good quality people simply never find out about these opportunities.
Once they are recruited, ensuring that subjects complete the study and comply with the directions of the sponsor is a huge ongoing problem, and noncompliance translates to up to $75 billion per year in lost sales to the pharmaceutical industry.3 Among noncompliant subjects, almost a full quarter of them say that they simply forgot to take their medication.4
Pharmaceutical sponsors are often subjected to time constraints during a clinical study, but there are simple solutions currently available that remind subjects to take medication and attend clinical visits. Sponsors often send out fridge magnets with reminder messages, diaries with clinical visit dates already inputted, and other small items to serve as reminders to subjects. Additionally, letters and e-newsletters can be sent out periodically to remind subjects to attend their upcoming clinical visits or to inform them of changes to the study.
Subjects may decide to leave a study for a number of reasons. The product may have side effects that deter them from complying with the recommended regimen, in which case it is important to provide an appropriate level of information about the expected effects of the product. Alternatively, they may suffer from lack of incentive or feel asymptomatic, stopping the medication altogether. In such cases it is important to renew motivation, such as by creating a goal that is personal to the subject and that serves as a reason for participating in the study. Another common reason for noncompliance is lack of enthusiasm on the part of a subject, which can be caused by behavioral or psychological changes as a result of the study. In this case, educating and increasing awareness during particular phases of the study can help to remotivate subjects. Reinforcement points can be tailored to include more items such as news about the disease or reminders of the benefits of remaining in the program.
Text messaging is a personal and inexpensive way to communicate with subjects.
Although these methods can improve subject compliance and retention, they do not require interaction from them, so there is a chance subjects may simply fail to respond to reminders or communication from the sponsor. As new technologies emerge, they can be used to tackle these issues.
As mentioned, cell phone technology is rapidly becoming ubiquitous across the globe, and health care providers can now use these devices to overcome the obstacles of subject recruitment, retention, and compliance. Companies are taking advantage of the cell phone's popularity to develop cost-effective and easy-to-use solutions to communicate with and elicit a response from subjects. Such solutions use simple SMS functionality, which is included as a standard function on all cell phones without the need to download or install additional applications.
SMS messages and alerts are delivered directly to the subject participating in a clinical study via his or her own cell phone, resulting in a powerful and nonintrusive method for ensuring that subjects remember to take medication and stay on the program. This solution offers health care providers a personal and inexpensive outbound form of direct-to-subject communication and means that subjects can proactively and easily contact the sponsor via return text messages.
Such technology is now also being deployed along with location-based services to recruit, locate, and screen potential subjects for clinical trials and commercial programs. Traditional methods of subject recruitment generally result in a response rate of between 5% to 10%, but sponsors using SMS technology can see rates of more than 30%. In addition, recruitment results are delivered immediately, saving time in comparison to traditional methods, which can take up to weeks or even months to provide results.
Cell phone technology can be used to complement traditional advertising, and people can register for a trial by sending an SMS message to a short code, such as "Text TRIAL to 85342 to receive more details." Upon receipt of the SMS, multiple workflows can be activated, including a short SMS-based questionnaire about the age, sex, and condition of the person. Alternatively, a response can be sent that directs the person to the nearest recruiting center to be screened for suitability.
SMS technology is currently used by a number of large pharmaceutical companies in support of their clinical trials and marketing programs. Using cell phone technology, timely SMS messages can help to address subject noncompliance.
Within certain socio-economic groups, it is important that the physician prescribing the information is seen as the information "holder." In this case, SMS messages that are seen to be from the physician are extremely effective. Not only does this encourage communication without additional work on the part of the physician, it also makes subjects feel more valued and important. Information reinforcement is essential to improving subject compliance, and the SMS message can be personalized by the health care professional.
Pharmaceutical sponsors are also using cell phone technology to send medication and clinic visit reminders to subjects. Enrolled subjects receive timed reminders regarding their next clinic appointment, and these messages can be configured to prompt the subject to confirm whether they can attend the visit. SMS messages can also be personalized according to a subject's medication, dosage, and frequency to remind them when and how to take their medication safely.
In the highly regulated pharmaceutical environment, it is essential that any new technology be compliant with strict regulations in order to be suitable for use in clinical research. In the case of SMS technology, both data protection and collection are important issues, as well as the ethical implications of personally contacting subjects. For example, the cell phone technology provided by our company is fully compliant with both the U.S. Health Insurance Portability and Accountability Act of 1996 (HIPAA) and the EU Directive 2002/58/EC (a Directive on privacy and electronic communication). This ensures that all data are encrypted to 256 bits, subject consent is obtained before communication begins, and a simple "opt-out" service exists for subjects or sites. Additionally, the solution has full message tracking capabilities and generates delivery reports to guarantee the surety of receiving the messages, providing a full audit trail in line with these regulations.
Analysts are now predicting the demise of conventional SMS messaging in favor of 3G technology, such as cell phone-based email and instant messaging. In the next five years, it's likely these technologies will be adapted for subject communication in clinical trials. This will not only enable sponsors to send more engaging messages but will also increase the response types available to subjects, including photo and animated messages.
However, clinical studies are now increasingly outsourced to developing countries, particularly Africa, India, and Latin America. Although the number of cell phone users in these areas is growing, technology is often slower to develop. As a result, SMS technology will continue to play an important part in clinical trials in such geographies, since they will adopt 3G and associated technologies less rapidly.
Tim Davis* is cofounder of Exco InTouch, Greenway Business Centre, Harlow Business Park, Harlow Essex, CM19 5QE, United Kingdom, email:firstname.lastname@example.org and Patrick Hughes is executive director of the company.
*To whom all correspondence should be addressed.
2. Harris Interactive, www.harrisinteractive.com/news/allnewsbydate.asp?NewsID=941.
3. Datamonitor, "Disease Management and Drug Adherence: Strategies to support patients and enhance treatment persistence, July 2, 2007, www.datamonitor.com.
4. The Chodon Group, reported in NewJersey's The Star Ledger (7 August 2007).