备份站点：临床试验的终结者

Backup Sites:TheClosers of Clinical Trials By Darcy GrabensteinDirector, Content Strategy & Thought Leadership With baseball season in full swing in the US,this national pastime is on the minds of manyAmericans. So it’s only natural for me to viewthe clinical trial recruitment process in terms ofruns, hits, and errors. one to six or months for most clinical trials whencompared to initial baseline assumptions. Thepharmaceutical industry stands to lose between$600,000 and $8 million for each day of delay.1 To mitigate risk, most sponsors and CROswill conduct a feasibility assessment usinghistorical data sources and/or HCP outreach,and develop a proactive contingency plan thatquite often involves backup trial sites or evenbackup countries. Think of it as the reserve listfor pharma. With the increasing number of trialsbeing conducted (see graph), dwindling staffavailability at site, and trials involving diagnosticand technology complexity, the industry hasmoved to backup sites being the new normal.Backup or overage sites are usually broughtthrough the start-up process at the same timeas other sites but are not activated. These sites,later activated in the event that recruitment isnot going as expected, become what is knownas add-on or rescue sites, included at the clinicalequivalent of the ninth inning. It’s all an effort toload the bases. Sponsors must cover all the bases when runningand recruiting for clinical trials; the process itselfhas become an exercise in risk managementand mitigation. It starts in the planning stages,developing protocols and inclusion/exclusioncriteria that are specific to the research beingconducted but not so limiting as to rule outdiverse demographics and/or limiting to sucha small margin of patients that recruitingbecomes a “needle in a haystack” exercise. What happens, however, when a sponsor failsto hit its recruitment targets? A swing and amiss here can result in a delay of game, costingboth the sponsor and the industry as well asdelaying getting new, potentially life-savingdrugs in the hands of HCPs and patients.Recruitment-related trial delays tack on an extra When it comes to backup sites, it may be difficultto level the playing field. One dilemma sponsorsface is whether to inform a site that it is abackup. If a sponsor discloses this during theselection process, site staff may be concernedtheir site will not earn revenue. Conversely, ifa sponsor does not inform a site of its status,that could jeopardize the sponsor’s long-termrelationship with the site. Another school ofthought is that backup sites often put in theextra effort to recruit, in hopes they’ll be takenoff the bench and make the starting lineup forupcoming trials. There are also countries thathave extremely lengthy startup and regulatoryapproval processes; should sites in theseterritories always be relegated to backup status? Because of this, sponsors tend to exceed thenumber of sites estimated as necessary torecruit patients, which is costly. They must payfor ethics and regulatory submissions, site visits,documentation, and more. Many sites requirea stipend regardless of whether they recruit asingle patient ― this can often run to 30% overper-patient grant amounts. Riches warns thatsome are “serial startup sites” that pocket theup-front fee but ultimately do not recruit. Once sites are up and running, Riches says, asponsor is beholden to the sites to deliver whatthey promised in terms of patient numbers.However, external forces such as competingtrials are clinical curveballs and can be game-changers. “That’s why it’s important to choosethe right site in the first place,” she says. “Thegood news is now we have the data ― who’sdoing the trials, how many trials they haveconducted, which therapeutic areas, standard ofcare, the regulatory landscape, and upcomingtrials that might affect bandwidth.” Claire Riches, Citeline vice president of clinicalsolutions, says approximately 80% of patientscome from 20% of investigator sites. She notesthat some sites will fall by the wayside, requiringa pinch hitter, some will over-recruit, and somewill under-recruit. Among factors contributingthe most to costs across all clinical trial phasesare site monitoring costs (9–14%) and siteretention costs (9–16%).2 Riches says sponsors would prefer to avoid theuse of backup sites altogether. “If they pickedthe right sites from the get-go, they wouldn’thave to go this route. Accurate, data-drivenstudy feasibility is essential to determine atrial’s importance and relevance for a site andto evaluate a site’s capability and recruitmentcapacity.” In the past 10 years, Riches says the industryhas seen a drop in site performance. Thiscan be attributed to many reasons, includingincreased pressure, increased trial complexity,increased burden on site staff to use newtechnology platforms, fewer staff, less time toconduct trials, and limited availability of patientpopulations. References About the Author Darcy Grabenstein is Director, C