By Charles Romano and Ross Mason
Biotechnology research is emerging in Georgia through a financially buoyant and talented pool of professionals who bring great science, technology and jobs to the state. This industry is typically cost-effective for medical innovation while exploring novel products that can save millions of lives.
Speaking at the launch of a Georgia-grown research partnership recently, Gov. Sonny Perdue noted, “This partnership demonstrates the strengths Georgia provides industry through collaborations among its research universities, health care organizations and the Georgia Research Alliance.” This clear endorsement, combined with a relatively low cost of living compared to other states, should position Georgia high on the list of clinical research projects awarded each year.
How does Georgia rank for exposure to clinical research?
There are over 30,000 clinical trials noted as ongoing in the United States that are preparing to recruit patients or in the process of recruiting patients. Of these studies, 1,305 are conducted in Georgia or have one or more research centers in Georgia, among other states. Despite ranking 10th in overall population within the United States, Georgia is involved in fewer than 5 percent of these ongoing studies. North Carolina, which ranks 11th in statewide population, is 10th in the number of active, recruiting Phase 1 studies. Georgia ranks 17th, behind New Jersey, Tennessee and Florida.
Georgia boasts some of the nation’s best physicians and researchers, but it is arguably less likely to draw the best talents away from another state based only on an offer to help improve their speaking and publication history in the short term. The second criterion for selection of sites offers some opportunities that can be encouraged at the state and local level rapidly.
How does a research center in Georgia recruit patients for a clinical trial?
Beginning chronologically with the sponsor – pharmaceutical or medical device company, an academic center, a government agency or through foreign counterparts – a study concept is developed internally or through consultants. (Industry sponsors provided approximately 70 percent of funding for clinical trials in 2005.) Upon agreement for funding, some research into investigator site selection is done internally, based on historic studies by disease condition (also called indication), or outsourced to a contract research organization to perform a feasibility assessment. A feasibility assessment can comprise a few questions regarding the background of the investigator and their practice or multiple questionnaires that seek to assess a more accurate prediction of the ability of a research center to recruit the patients defined by the study parameters within the defined time.
For example, for a study in epilepsy in the site selection phase, a neurologist may be questioned about the number of patients seen by the practice as new or regular patients. The feasibility assessment may also seek to winnow the population at that site based on the inclusion/exclusion criteria defined by a study protocol, such as the kind of seizures experienced and how many are compliant with their medication.
This opportunity to describe a practice in terms of clinical trial potential sometimes goes unanswered due to time constraints at the site, lack of current data on their own populations, and lack of funding to do a proper search of patient populations. Worse, when an investigator does complete these forms, they may not fully consider the population of the study or competing practices and over-represent their recruitment. This counts against some sites in selection for future research.
Why is access to patient populations important to a sponsor?
Attempting to shorten the study length, sponsors and contract research organization spend several thousands, and collectively millions, of dollars each year on feasibility questionnaires and historical data on investigators. If a study requires 80 patients based on its statistical design, then 10 centers that can recruit one patient per month should finish recruiting for the study in eight months (given equal startup and many other factors).
A center with good access to the patients required for a study (and the ability to accommodate them while maintaining good quality) may be able to see 20 patients per month that qualify for a study. This level of exposure would allow them to recruit the study either as a single site over four months (half the time originally proposed) or, if a study limits the number of patients that can come from one site, reduce the overall time to recruit and collect data.
Shortened recruitment translates to a study that finishes sooner, potentially allowing a product to go to market faster or avoid further testing and investment. Faster delivery to market can mean thousands of dollars per day to a sponsor. For a recent trial managed in Georgia, the sponsor gained approximately $3 million in sales per day for filing a submission (summary of clinical trial data and other science submitted to a government regulatory body) and obtaining approval with the Federal Drug Administration earlier than planned.
Why would improved industry access to a patient population for a study benefit Georgia residents?
It is important to note that while patients may see a therapeutic relief of symptoms from their disease in a clinical trial, few do. The drug may not work well for them, may be at a dose being explored but too low or too high for them, or the side effects from the product outweigh the interest of their health to remain in the study.
Perhaps the least explored benefit of a clinical trial, however, is the benefit to patients from simple participation and the medical assessments typically done. Sponsors want to ensure that any underlying illness a patient has prior to exposure to the investigational product does not transfer as a cause by the product in testing. In more simple terms, if you have a common cold and start a clinical trial with a stuffy nose and fever, the new product has nothing to do with your cold and shouldn’t be blamed (unless it makes the cold worse).
Considerable resources are spent to assess patients’ health through thorough medical screening and physical exams. Depending on the indication, this screening may involve tests beyond the standard of care for diagnosis, such as carbon monoxide breathing tests for smokers. This screening is usually accompanied by laboratory screening for health indicators such as elevated white blood cell count (a possible sign of infection), X-rays, MRIs, sleep studies, etc.
Though not included with all studies (some are quite simple), this level of testing is done at no expense to the patient and usually without a requirement of medical insurance. During one industry study in New London, Conn., a participant was discovered to have an elevated hormone level. The sponsor physician encouraged the investigator to explore this with further testing, which included an ultrasound, an MRI and a consultation with an OB/GYN oncologist at the cost of the sponsor. The participant had no insurance nor, according to the investigator, would she have sought this level of scrutiny if not for her voluntary enrollment in a clinical trial. This is a good example of how a study can benefit a patient, although there are many cautions for a patient’s participation in a clinical trial.
Medical device and drug trials are conducted to gather information that helps physicians determine whether a product is helpful or better than another product for a given disease or condition (or prevention of a disease or condition). Unfortunately, over the course of study or after it is completed, some products are shown to actually make patients sicker or do not improve their conditions. In rare cases, there have been deaths attributed to experimental drugs. This is the reason patients in clinical trials are followed so closely and are advised of these risks (in a process called “Informed Consent”) in lay terms approved by ethics committees before they may touch, taste or smell an investigational drug or medical device.
The conservative financial impact translated into medical dollars for Georgia is approximately $900 per patient per study in services provided at no cost to the patient. This does not include cost savings from early diagnosis of underlying diseases and patient education. At this rate and with the current trial exposure (assuming only three patients per study and 1,500 studies currently running in Georgia), the ongoing financial impact on patients currently enrolled in clinical trials in Georgia is approximately $4.1 million per year in free medical services.
An effort to increase the number of Georgia residents in clinical trials (for which they qualify and are eager to enroll) by 20 percent each year could grow this under-recognized pipeline of medical service by approximately $1 million a year, conservatively. Consider that less than 0.1 percent of Georgia residents (2008 Census estimate) are currently enrolling in a clinical trial.
In addition, expanding patient recruitment in clinical trials by 10 percent per year in Georgia would increase clinical trial budgets for Georgia investigators by approximately $8,000 per patient in direct compensation from industry. Currently, approximately $30 million is spent in Georgia on clinical trials in per patient fees and materials. An increase of 450 subjects recruited in Georgia (1,500 studies x 3 patients = approximately 4,500 patients x 10 percent increase) would mean $3.6 million per year in additional industry spending in Georgia.
Worth a separate paper in itself, Georgia’s rich ethnic diversity ranks it in the top three states in the country for metropolitan areas with high rates of minority patients. Some clinical trials that can boast demographics that represent greater ethnic diversity lend better credence to their arguments when undergoing scrutiny by peer reviewers. “To not have proper representation of impacted populations creates issues of scientific integrity and relevance,” one researcher notes. In fact, some large studies are kept open with lengthier recruiting to allow greater influx of minority populations, slowing the product getting to market.
How could a rural Georgia county benefit from a clinical trial portal for the state?
Clinical trials are written and described in a common document called a study protocol or trial design summary. This protocol attempts to ensure that patients are treated similarly (almost always according to present-day standards) and explain the steps to be taken to collect data from patients for the trial. A protocol does not stop a physician from rendering the best care for a patient, even if it departs from the steps laid out in the protocol. Rather, it provides a path to capture those steps where a patient is treated differently than the others. Some protocols can bring in best practices observed in other regions or offer a technology previously denied the institution for lack of funding. During a recent study, a Top 5 pharmaceutical company placed 250 echocardiogram machines (worth $250,000 each) at institutions around the country (both rural and urban) for three years. For the sponsor, this ensured the data at all of the research centers was captured in the same manner. Not all trials enjoy that degree of technological investment but most studies use some form of innovative technology.
Good clinical practice guidance material usually requires that the staff in these studies be trained by the sponsors of the research on the new device, system, software or procedures before patients are exposed to them. Physicians and staff taking part in these studies are learning about new medicines and medical devices years before they are available on the market. This builds their knowledge of treatment options for patients and potentially affords them the opportunity to be subject matter experts on that product or class of treatment when their parent institutions or private practices are deciding on new products or devices to include in their formularies.
Finally, visualize a city or county with an uninsured population of 30,000. At any time, approximately 50 percent of a given population qualifies for a clinical trial but doesn’t know it. Reaching just 5 percent of these people and informing them of the availability of free medical screening and possibly free medical care for a longer period (if they qualify for the study), has the potential to give 1,500 people assistance at no cost to them or the state. Even if the trial is run in a different county, most trials pay participants for travel costs. For a rare disease, some studies will recruit across state lines to ensure an adequate number of study subjects.
How could sponsor access to Georgia patient populations be improved?
Relying on physicians and busy practices to constantly assess their patient populations can push a cost burden on them that would not be relieved until selected for a clinical trial or funded for their own research, many weeks or months after the study is awarded. Poor interpretation of HIPAA (patient confidentiality) laws have had the unintended consequences of putting off-limits some practices’ chart reviews for the intent of assessing patients for appropriate clinical trials.
HIPAA includes a major provision that requires covered entities (hospitals, physicians, health plans and other entities that handle patient information) to obtain confidentiality documentation from researchers before disclosing health data. This section of the law, which took effect as part of the overall medical privacy law in April 2003, was intended to ensure that patients’ protected health information would not be inappropriately disclosed or used during the course of a research trial. Contacting eligible participants for clinical trial recruitment is a challenge and HIPAA regulations have made this process more complicated. Pre-HIPAA, patient lists and their contact information were accessible for review, and clinical study personnel were able to identify and subsequently contact eligible participants. Conversely, post-HIPAA, the contact information of potential participants cannot be accessed without the participants’ explicit authorization, a clear hindrance to the contact and clinical trial recruitment process. The burden has shifted to the health care provider (who now becomes the recruiter), already inundated with patient care responsibilities and time constraints, to introduce the study to the patient and obtain their consent for subsequent contact at a possible later date.
A better solution may be a statewide registry, supported by the state and encouraged at the institutional level, that allows patients to enter their information for use in potential clinical trials. Consider a new research site that must answer a sponsor’s initial question, “From where will you gain new patients for a study?” Research sites around Georgia could contact the Georgia Trial Registry and query the number of patients that meet their clinical study requirements in their ZIP code and, for a small fee, highlight their study in the next communication with patient subscribers. The material from these sites, depending on how detailed and the stage of the studies, is usually approved by institutional review boards (IRBs) for ethical concerns before they can be presented directly to patients.
By calling a toll-free number or completing information via a Web-based client, patients would access information on studies that fit their profile and have information directed to their e-mail inbox or telephone.
Community centers and libraries would be educated on allowing Georgians with limited access to phone or Internet service to use the free-to-enroll Web site or toll-free phone entry. For example: A charter, inner-city school has residents suffering from untreated or under-served disease may reach out to them (or their guardians as appropriate) and offer to enroll them through a Georgia clinical trial portal for notices of clinical trials that are recruiting new patients that fit their interests locally.
There is a small chance this interaction may become negative. Historically, family members can enter their friends or loved ones with good intentions or as a practical joke, an action typically thwarted at the interview level. An ill-intended marketing firm also may simply seek access to patients by their indication to launch an advertising campaign (similar to spam). Allowing the patients to see studies where they may qualify or notifying them with contact information for the research site puts the burden of voluntary approach to an investigational site on the patient who wants to learn more about a study. State support of this type of institution also raises concerns regarding the privacy of individual health information. A Georgia clinical trial portal may be funded by state dollars, but it should still show a clear commitment to the privacy of subscribers and limit access to their data from non-mission exposure.
How does Georgia rate for clinical trial costs?
The top states for biomedical research are Texas, California, New York and Massachusetts. Not one of these states ranks lower than Georgia for the cost of a physical exam, an X-ray or patient education. If a Georgia investigator could demonstrate improved patient access that competes with other population centers and a cost model that returns dollars to their research and development budgets, it would be very difficult to defend a site list that did not include Georgia researchers. Consider how many studies move off-shore simply because costs are reduced (though somewhat offset) by the burden of sponsoring them abroad.
The cost of an ECG, an EEG and venupuncture may be far less in Sao Paulo, compared to Boston, yet the cost difference is far less compelling when compared to Georgia rates, which are lower than other U.S. states.
Despite the clear advantage for Georgia in a cost comparison, industry does not rank site costs for a new clinical study as the most important decision factor compared to the need for access to patients and the publication/peer leadership of the physicians and doctors that will do the research.
Increasing the access of patients to clinical trials in Georgia is an immediate way to improve the standing of Georgia research professionals in clinical trials, improve options for patients that want to explore clinical trials and take advantage of industry-paid health care. This approach also improves the exposure of Georgia physicians and health care teams to novel products years in advance of market exposure, simply because they are able to recruit studies more rapidly.
Charles Romano is the director of Clinical Operations and Government Affairs for Peachtree BioResearch Solutions, based in Smyrna, Ga., and is on assignment to St. Joseph’s Translational Research Institute in Atlanta. Ross Mason is a Senior Fellow at the Georgia Public Policy Foundation and chairman of the Healthcare Institute For Neuro-Recovery & Innovation. The Georgia Public Policy Foundation is an independent think tank that proposes practical, market-oriented approaches to public policy to improve the lives of Georgians. Nothing written here is to be construed as necessarily reflecting the views of the Foundation or as an attempt to aid or hinder the passage of any bill before the U.S. Congress or the Georgia Legislature.
Thank you for the great work that the Public Policy Foundation is doing across our state setting a wonderful example. I first ran for the Senate in 1994, and the Foundation was that resource I called upon to be a great help to me as we were articulating positions and formulating public policy initiatives. We appreciate very much your leadership and all that you stand for.