Contract Research Organizations: Radiology’s Newest Revenue Stream
In the not-too-distant past, the use of imaging as an endpoint in clinical trials was at best considered a novel approach by pharmaceutical and device manufacturers alike. The times, however, are changing, and bringing with them a new revenue stream for the radiology community. Opening the floodgates are partnerships with nonprofit and for-profit contract research organizations (CROs) that have begun to recruit clinicians and academic physicians aggressively to serve as independent blinded readers. Compensated by sponsors primarily on a per-study or per-service basis, these organizations pay third-party blinded readers what one executive deemed a fee that could average $2,000 to $4,000 per day, approximately. Radiologists jumping on the bandwagon find themselves assessing images that involve a wide range of modalities and questions, depending on the CRO.
Bruce J. Hillman, MD, FACRIndustry analysts at Goldman Sachs and Frost & Sullivan peg the worldwide CRO market as growing at a rate of 15% annually for the foreseeable future, up from $17.8 billion in 2007. Bruce J. Hillman, MD, FACR, is chief scientific officer of ACR Image MetrixTM, a CRO based in Philadelphia, Pennsylvania. He affirms, “Demand for imaging CRO services is literally exploding because imaging endpoints are now being recognized as a way to make clinical trials much more efficient. Manufacturers realize that imaging can hasten the process of obtaining trial results and limit investments in seemingly ineffective drugs and devices.” A for-profit entity, ACR Image Metrix is located at the ACR Clinical Research Center in Philadelphia. The ACR Research Center also houses Radiation Therapy Oncology Group and ACR Imaging Network (ACRIN), which are largely funded by large National Cancer Institute grants. ACR Image Metrix draws on the more than 160 staff of the Clinical Research Center, purchases access to the ACR Core Lab technologies, and maintains a broad network of leading institutions and researchers to serve industry clients. Changes in FDA directives as to what constitutes evidence of therapeutic agents’ effectiveness have also pushed the envelope for CROs and, in turn, contract radiologists seeking to augment their service lines, according to Rick Taranto, vice president of business development, WorldCare Clinical, Boston, Massachusetts. Founded in 1992 as part of the Massachusetts General Hospital (MGH) department of radiology, the organization became an independent for-profit company three years later. ProScan Imaging, LLC, Cincinnati, Ohio, acquired 51% ownership of WorldCare Clinical from its parent company, WorldCare Limited, in 2006. Many Questions and Many Modalities Providing image interpretation is, not surprisingly, the core component of a CRO’s business. Some organizations focus on a wide spectrum of modalities to address functional and anatomical questions alike. BioClinica Inc, Newtown, Pennsylvania, represents a case in point. Its offered modalities include:
- angiography (quantitative coronary and quantitative vascular studies);
- CT (angiography, lung-density/volume studies, and quantitative CT);
- dual-energy x-ray absorptiometry (bone-mineral–density assessments, body-composition studies, and hip structural analyses);
- MRI (angiography, body/neurological studies, cardiac studies, and dynamic contrast-enhanced MRI);
- nuclear medicine (planar studies, multiple-gated acquisition scans, SPECT, and whole-body studies);
- optical-coherence tomography;
- ultrasound; and
Ronald Berg, CEOWalovitch and Taranto note that a small portion of WorldCare Clinical’s commissions involves smaller trials for companies that may have only one or two products and wish to outsource full trial management to a CRO. The lion’s share of its clientele, however, consists of a combination of large pharmaceutical and biotechnology concerns. “Our next step, which we’ve already initiated, is expanding into the medical-device side of the business,” Taranto states. In contrast, RadPharm, headquartered in Princeton, New Jersey, caters almost exclusively to pharmaceutical companies of all sizes: “Devices,” CEO Ronald Berg says, “are not our biggest point of emphasis.” RadPharm’s in-house board-certified radiologists and nuclear-medicine physicians evaluate imaging data, both qualitatively and quantitatively. Image analysis is performed for traditional modalities, including CT and MRI, as well as for gamma-camera imaging, PET, PET/CT, and SPECT/CT. “Oncology therapy, sometimes using anatomic imaging as a subset, is our area of core competency, and as a result, that is where we’re investing the bulk of our efforts,” Berg elaborates. “This makes sense for us, given that imaging is used to the greatest extent to assess the efficacy of most cancer-treatment compounds under development.” The same is true of RadMD, headquartered in Doylestown, Pennsylvania, and serving a clientele of medium-to-large pharmaceutical companies, as well as small biotechnology manufacturers. Most of its medical imaging commissions are in the areas of oncology and neurology, according to cofounder Kokhan Shamsi, MD. Its menu of modalities is similar to that of RadPharm. Beyond image analysis, the CRO business model calls for a spate of other services built around the design and execution of drug and device trials. While the roster differs from organization to organization, it can encompass defining and developing imaging strategies and protocols, optimizing imaging endpoints, and configuring site and independent image-review strategies.
Kokhan Shamsi, MDOn the list, as well, are independent review charter development; imaging site selection and qualification; and attendance at regulatory meetings. Rounding out the list are preparation and review of study and expert reports, regulatory-submission support, mining of postapproval imaging data, and imaging-enabled marketing support. Some CROs will also develop and/or participate in expert and consensus panels. These functions can, and do, present significant potential obstacles. “In design and execution, we must take into account a huge number of variables, including the fact that imaging is being conducted at many sites, each with a different standard of care and cost-reimbursement structure,” Berg says. “We also have to think of these variables as they relate to the modality we’re using, as some modalities are more difficult than others. Otherwise, there is the risk of winding up with a failed trial.” Shamsi corroborates Berg’s comments. He adds that creating protocols that are harmonized across multiple sites, and then monitoring them, constitutes a roadblock that continually crops up in the course of CRO operation. So does helping sponsors understand the cost effectiveness of using different modalities. “Often, getting across the point that imaging may reduce the long-term cost of running trials can be a challenge, too,” Shamsi observes. The Road to Opportunity Just as the breadth of CRO business models, opportunities, and challenges has evolved in different directions, so, too, has the structure of contractual arrangements into which radiologists can tap when adding CRO image reading and related functions to their service lines. The bulk of opportunities comes under the independent-contractor umbrella, with CROs drawing from pools of experts as they are commissioned to assist with clinical trials. Reader selection occurs in accordance with a range of criteria, including (but not always limited to) the expert’s subspecialty; the study’s clinical, time, and other parameters; the study subjects; and the type of drug or device undergoing evaluation. There are subtle variations. Some opportunities are open to academic and clinical readers alike. RadMD, for example, maintains contractual relationships with approximately 600 independent image reviewers worldwide, among them radiologists, oncologists, cardiologists, pathologists, and medical imaging physicists. Its base of radiology resources encompasses practicing and semiretired clinicians and academic personnel. Cofounder Richard Patt, MD, says that the organization is actively seeking to expand its network on the radiology front and beyond, adding that candidates must not only be board-certified and licensed in the countries in which they practice, but must meet stringent screening criteria as well. BioClinica and ACR Image Metrix follow similar models, yet options for partnering with both CROs are seemingly more limited. Academic radiologists constitute approximately 75% of BioClinica’s base of contracted radiologists, as extensive involvement in clinical research is more suited to the operation’s emphasis on phase 3 studies, according to Weinstein. Clinicians must generally practice within a subspecialty. “If we’re looking at the effect of something on the head and neck, we want someone who lives and breathes heads and necks all day long,” Weinstein explains. He adds that this is particularly important when assessment results can be subjective or semisubjective, such as the rating of joint-space erosion on a scale of 1 to 5. In addition, BioClinica’s mode of operation calls for selecting a minimum of two experienced independent readers from different institutions for each clinical-trial management system. CVs are made available for client review and approval prior to the final reader selection. For its part, ACR Image Metrix is primarily leveraging alliances with several hundred radiologists and imaging scientists forged since the inception of ACRIN in 1999. Management has begun identifying additional private practitioners and academic radiologists to bring into the fold, using their acceptance of the ACRIN model as a primary qualification criterion. Hillman notes, “We are calling on radiologists and are involving private practitioners and academics in what we are doing. Prospects, however, would need to wait to be contacted by us, rather than vice versa.” Other CROs take more of a hybrid approach to hiring and working with independent radiologists. WorldCare Clinical has a pool of approximately 50 to 60 outside clinicians worldwide who serve as adjuncts to the organization’s team of 26 to 28 in-house radiologists. Practitioners can also get in the door via study sponsors, which retain the prerogative of requesting that images used as part of ongoing trials be read by the radiologists of their choice. WorldCare, however, draws equally on partnerships with clinicians at the MGH department of radiology and at the University of Chicago Medical Center in Illinois, particularly in the areas of oncology, neurology, neuropathology, and nuclear medicine. All WorldCare Clinical trial radiologists are required to be trained in a specific therapeutic subspecialty; advanced modality expertise in CT, MRI, ultrasound, PET, or nuclear medicine is considered desirable. The Reproducibility Challenge Getting a foot in the door at a CRO necessitates not only satisfying such requirements as board certification and expertise in therapeutic subspecialties, but a willingness to undergo training and testing. Much of the latter has been implemented to assist CROs in grappling with one of their most significant obstacles in providing imaging-related services to drug- and device-trial sponsors: reproducibility. “Contrary to what some people may believe, it isn’t the modalities that pose the biggest challenge to us,” Walovitch says. “The biggest challenge centers on how to carry out trials to achieve reproducibility in reader performance, whether we are talking about a single radiologist and a single modality or a double-blind interpretation with adjudication using multiple modalities. It is critical for a study’s success to have a high level of agreement across readers and good consistency within assessments made by the same reader. This is the area in which CROs provide the greatest value, and everyone needs to be on board in terms of it.” Following training, radiologists affiliated with WorldCare Clinical receive sets of scans that they are asked to read more than once to ascertain reproducibility. Additional assessment occurs through WorldCare Clinical’s application of version 1.0 of the imaging-performance metrics of the nonprofit Metrics Champion Consortium (Carmel, Indiana), executed through its WorldProTM technology solution. It involves statistical analysis to evaluate reader performance and reliability. Results appear in the form of a study newsletter, which helps to foster reproducibility by communicating case-study, reader-performance, and operational measurement data. WorldPro itself consists of an intuitive image-upload tool, a customizable database, and a Web portal that centralizes all trial activity among sponsors, trial sites, and WorldCare Clinical’s project managers. In a related vein, blinded readers connected with RadMD access training through the CRO’s Blinded Reader and Investigator Training Institute (BRITI). They can expect exposure to peer-reviewed educational modules consisting of lectures on clinical development, the blinded reading process, and various imaging evaluation criteria; both testing and training are administered online or on-site, individually or in groups. BRITI tracks detailed training parameters for each participant and provides certification upon completion of specific curricula. Moreover, a new initiative, launched in summer 2009, affords blinded readers (as well as clinical-trial personnel and on-site investigators) additional opportunities to take a broad range of accredited CME courses in the area of medical imaging. The courses are offered through BRITI, in conjunction with the International Center for Postgraduate Medical Education, Ithaca, New York. Clinicians and academic radiologists may be asked to undergo training using customized modules designed for specific trials. “With the explosion of the use of medical imaging in clinical trials, there has come a greater need for formalized training of clinical-trial personnel involved in image acquisition and evaluation,” Patt says. “A clear understanding of the clinical development process, specific knowledge of various evaluation criteria, and an understanding of pertinent regulatory requirements are critical for clinical-trial professionals who are participating as site investigators or are performing independent evaluations of imaging-trial data.” Patt and others foresee that imaging will play an even more significant role in clinical trials as an increasing number of sponsors embrace it as a means of assessing the efficacy of drugs designed to treat depression and similar conditions. As this occurs, there will be a concurrent heightened need for contract-radiology services. “It will,” Shamsi concludes, bode well “for all concerned.” Julie Ritzer Ross is a contributing writer for Radiology Business Journal.