Patient recruitment poses problems during many clinical studies. CenterWatch, for example, estimates that recruitment accounts for a quarter of the time of a typical clinical trial. ClinPhone cites other sources suggesting that 80% of studies don’t meet their enrolment targets, that recruitment problems account for 45% of delays in clinical trials and that keeping a study running costs around $40,000 a day.
So a 100-day delay costs $4 million: and this ignores the opportunity costs associated with the lost days that the drug could have been on the market. CenterWatch reports that each day an average drug is delayed from reaching the market is worth around $1.3 million in potential revenue. The loss increases up to $11 million daily for blockbusters.
The growing number of studies performed in ‘non-traditional’ parts of the world is one consequence of these recruitment problems. Contract research organisations active in Central and Eastern Europe say that recruitment is between six and eight times faster than in either Western Europe or North America. On the other hand, many emerging areas encompass a diverse range of legislative frameworks, cultures and languages, all of which potentially influence recruitment. So, not surprisingly, sponsors and vendors are exploring numerous other ways to enhance recruitment and identify barriers to greater participation.
There’s compelling evidence that fewer patients take part in clinical studies than you might expect. A paper in the Journal of Medical Internet Research recently commented that, for example, only 2%-4% of adults with newly diagnosed cancer participate in clinical studies. Certainly, numerous factors influence recruitment. For example, a study of breast cancer patients, published in April’s Journal of Clinical Oncology, suggested that reducing the drawbacks of participation, especially travel time, and improving physician communication may increase participation.
The benefits of mass mailing
Against this background, educational and marketing agencies work with sponsors to inform and train physicians about the best way to recruit and retain patients. They also produce increasingly sophisticated patient resources – including multimedia presentations and websites – to encourage recruitment and retention, as well as to ensure that consent is as well informed as possible. During long-term studies, patients may receive regular newsletters, lunches, diaries, and so on. Such approaches have proved especially useful in recruiting and retaining elderly people into clinical studies.
Carefully targeted strategies can overcome some of the barriers, as illustrated by a recent paper by Messer et al in International Urology and Nephrology. They used a mass mailing to recruit healthy, continent, post-menopausal women aged 55 to 80 years to assess interventions aiming to prevent urinary incontinence. The overall and positive response rates were 4.8% and 3.3% respectively. Of those that agreed to participate, 37.6% were eligible on telephone screening.
The authors suggest that “careful planning, adequate resources up front, and ongoing review of recruitment at each phase” were responsible for the success of the mass mailing. For example, the researchers purchased a mailing list that contained only households that included women aged at least 55 years living near to the clinical sites. This minimised transportation problems. Furthermore, the researchers designed the flier to “sensitively” present “an interesting and understandable message” and “included a postage paid return postcard” that only took a few minutes to complete.
Similarly, the Women’s Health Initiative - founded in 1991 to investigate the most common causes of death, disability and impaired quality of life among postmenopausal women – aimed in one study to enrol 20% of its almost 162,000 recruits from ethnic minorities. They didn’t quite attain this challenging target, but still managed to enrol 17.5% of the cohort from ethnic minorities, a group traditionally under-represented in clinical studies.
Once again, mass mailing generated the best response. Among minority women, word of mouth and referral from friends was the second most successful strategy. White women preferred newspapers and printed materials. With the increasing recognition that clinical studies need to enrol an ethnically diverse population, such insights can aid recruitment.
The online approach
Nevertheless, the low response rates with traditional recruitment methods have encouraged vendors and companies to explore ways to improve recruitment. Online recruitment is, perhaps inevitably, one way in which companies and vendors might improve participation. Some websites now allow patients to register their demographic data. The system then matches the patient with any appropriate study. In some cases, the patient can enter their details into a secure database and the system can automatically notify patients when a sponsor posts an eligible trial.
Certainly, internet-based approaches can be effective. According to research published in the Journal of Medical Internet Research, OncoLink, which is run by the University of Pennsylvania, matched 627 patients suffering a variety of malignancies to a clinical study between January 2002 and April 2003. Surfers can now visit numerous sites to see if any studies attract their interest.
The home page for Centerwatch says the site offers details of over “41,000 active industry and government-sponsored clinical trials.” While recruitment is open, the sites include contact information.
Nevertheless, there are suggestions that web-based approaches may enrol from a different population than those recruited through conventional methods.
A study published in The Breast Journal in July compared attitudes towards clinical studies among 157 patients attending a radiation oncology clinic in Philadelphia and those who search for information on OncoLink. Surfers tended to be more interested in clinical trials testing new drugs or treatments than those in the clinic: 53% and 17% respectively. On the other hand, more patients at the clinic would need a greater than 50% chance of benefiting to participate in the study than those on the web: 52% and 25% respectively.
Furthermore, 65% of those at the clinic, compared to 38% of surfers, would require a less than 10% of chance of suffering serious toxicity to consider enrolment. Additional studies are needed to characterise whether there are similar differences in other clinical areas and in other parts of the world.
Fingers do the enrolling
According to the Government’s Expenditure and Food Survey, 78% of households owned at least one mobile phone in 2004-05. And landlines are, obviously, ubiquitous worldwide. Given our love affair with telecommunications, perhaps it’s not surprising that interactive voice response services offer another effective approach to recruitment and a growing number of vendors offer these services.
ClinPhone, for example, works with agencies to develop advertisements asking patients to participate in a clinical trial and complete an IVR qualification instrument. Subjects record their name and telephone number during the call. Study sites access the patient records by calling the IVR system. The system offers toll-free access from over 80 countries and 70 different languages and ClinPhone also offers a web-based version (interactive web response). Such systems are particularly effective for sensitive medical conditions, such as erectile dysfunction, where patients might be reluctant to consult a general practitioner or when delivering complex clinical assessments. The benefits are, however, not confined to niche areas.
In April, Covance launched its Express Suite of IVR services, which addresses the most common patient enrolment problem – randomisation - and drug supply management needs by building a system from reusable, off-the-shelf modules. This means that the system can be up and running within 10 days of finalising the spec. The Express Suite is suitable for trials or studies with fewer than fifty sites, up to five drug supply depots or geographies, and an expected duration of up to two years. The system captures screening, screen failure and enrolment in real-time.
None of these offers a simple solution to every patient recruitment problem you’ll face. Indeed, in some cases you may need to combine low-tech mass mail approaches and high-tech IVR and web-based solutions to reach the number and diversity of patients increasingly requested by regulatory authorities. But there seems to be a common theme: make things as simple as you can for patients and recruitment will rise.