Discovering Medicine for your Pain Practice through Clinical Research
Paul Lynch, MD, Tory McJunkin, MD, Ryan Tapscott, PhD, Trudy Madan, MHA, & Sheri Campbell
Dear Arizona Pain Specialists,
I recognize the technologies of pain management are always changing. I want my practice to be innovative – not just reading about the latest breakthroughs, but actively involved in finding them. Should I consider bringing clinical research trials in-house? How do I involve my practice in research and what do I need to do to be successful?
Unsure About Research
While there may always be debate nationally about whether healthcare should exist as a universal or private entity, we agree healthcare is a necessity. Humanity depends upon, wants, and needs good healthcare without hesitation. As the healthcare industry develops and expands in various sectors, such as nursing, healthcare services and products, job opportunities broaden in response. Such innovation is why healthcare is one of only a couple industries that have continued to grow during the economic downturn in the United States.
Clinical research is regarded as one of the fastest growing sectors of biotechnology and pharmaceuticals; it is an imperative segment that supports growth in several divisions of the industry. Clinical research is considered a necessary component for these particular healthcare sectors to thrive because it provides insight into new medications and treatments for varied illnesses. Without research, the field would remain stagnant. The clinical research industry requires many spheres of professional collaboration. Such demand for new technologies, paired with professional collaboration, has created continuous growth in this industry – logically resulting in the continued creation of career opportunities.
Clinical research is a unique in the need for collaboration of fields; to successfully conduct a clinical research trial, experts from many areas must work together. Such groups include but are not limited to: clinical research organizations, pharmaceutical sponsors, and physicians. Essential positions fulfilling these specific needs include: clinical research coordinators (CRC) and clinical research assistants (CRA) — who work on research study teams with physicians. Clinical research requires a successful integration of medicine and business by providing opportunities for employers, physicians, patients, and pharmaceutical and corporate research companies.
During the past 20 years, the science of performing clinical research has evolved. The pharmaceutical industry has seen mergers, acquisitions and layoffs. However, clinical research is thriving. Clinical research organizations (CROs) have seen consistent growth in revenue. As unemployment continues to rise, clinical research organizations are seeing the benefit of increased patient involvement. The following examples have been given by patients for their reasoning in participating in recent research:
- Participants gain access to new medicine, therapies, and/or medical devices before they are available to the public.
- Participants of clinical research are given an additional treatment option that may not otherwise exist.
- Investigational products may prove to be a more effective treatment than the current standard of care.
- Participants receive frequent and in depth individual medical attention from a research team of doctors, nurses, scientist, and other health professionals.
- Participants feel heroic for contributing to the advancement in the medicine.
When a patient chooses to participate in clinical research, he/she may receive the following services at no cost: medications, devices, supplies, medical exams, and laboratory and diagnostic tests. Patients may also receive compensation for their time and travel. A recent trend shows more patients are looking for ways to earn additional income.
Clinical research is essential to the development of new medications, new treatments, and new medical devices. Such trials may be categorized as one of the following:
- Treatment studies: test new treatments, new combinations of drugs, or new approaches to surgery and/or therapies, such as radiation or physical therapy.
- Prevention studies: investigate better approaches to eliminate disease which may include medicines, vaccines, or lifestyle changes, among other things.
- Diagnostic studies: evaluate and determine better methods of testing, or procedures for identifying a particular disease or condition.
- Screening studies: investigate and determine the best way to detect certain diseases or health conditions.
- Quality of life studies: (or supportive care studies) explore and measure ways to improve the comfort and quality of life of people with a chronic illness.
Carefully conducted clinical research studies are seen as the fastest and safest way to find effective treatments, improve standard of care, and identify methods to improve health care. In the search to understand, prevent and treat disease, clinical studies involving volunteers of a vast variety of ailments play a vital role. Participating in clinical research is essential for the development of new medications and new treatments. Not only do participants experience full benefits at no personal expense, they also have the satisfaction of knowing that results from research studies may help others in the future.
GETTING STARTED IN CLINICAL RESEARCH
How do I find clinical trials?
Websites, such as CenterWatch.com or Clinicaltrials.gov, can help those interested in participating find clinical trials. On Clinicaltrials.gov you can perform keyword searches based on topic and location (e.g., chronic low back pain & Scottsdale, Arizona). If you find a trial that you are interested in, reach out to the point of contact listed to inquire about becoming a potential study site. There are also Internet databases where physicians can submit practice information, and select diseases and illnesses they would prefer to study based on their patient population. Other possible means of identifying clinical trials include contacting drug or medical device companies.
Moreover, there are companies that exist to help match practices with clinical trials. CROs are contracted by study sponsors to find appropriate study sites and conduct the studies for the sponsor; site management organizations (SMOs) help physicians identify and apply for clinical trials.1 These organizations vary greatly in the services they provide to physicians who are looking to become principal investigators. For example, if a physician wants to conduct research, but has little to no research staff, a SMO can provide complete management of the site’s clinical research, from assisting in IRB application completion and other documentation, building a site’s needed infrastructure (including staff support and equipment), as well as assisting in patient recruitment and the logistics necessary to build the study protocol into a practice’s workflow. On the other hand, if a practice is well equipped with a coordinator, research staff, and other infrastructure needed to be successful, a SMO can serve as a liaison between the clinical trial sponsor and the site. SMOs such as Synergyst Research are great at locating clinical trials that match a practice’s patient population, and are instrumental in helping a site complete all necessary regulatory documents to apply for a trial, prepare for a pre-study site qualification visit, negotiate the study contract, and excel at ensuring a site is recruiting and enrolling patients.
Identifying Research Personnel
Finding interesting and appropriate clinical trials is only the first of many steps to conducting clinical research. There are a number of vital personnel that you will need to ensure the success of clinical research at your practice. These include a principal investigator, study coordinator, and sub-investigators. The role of principal investigator is normally filled by an MD whose responsibilities include, but are not limited to: making medical decisions, ensuring proper care is given to study patients according to the study protocol, adhering to numerous regulations and other ethical standards for human participant research and protection, and controlling and accounting for study drugs.2,3 Many times new physician-researchers fail to realize the extensive management and documentation inherent to clinical trials; they begin a clinical trial scrambling to try and accommodate these demands. It is important to have a competent study coordinator who’s designated to handle the day-to-day clinical research tasks. Physicians serving as principal investigators are generally too busy seeing patients and managing their business to also handle the day-to-day clinical research tasks, so a competent, dedicated coordinator can take a lot of pressure off the principal investigator over the course of a clinical trial.
At Arizona Pain Specialists, a PhD serves as our research director. He arrived to our practice with the requisite skill set needed for us to be successful in clinical research, which has saved us many headaches in the long run. Not every site will be able to hire a PhD-trained researcher, but there are certain traits one can seek when hiring a study coordinator. These include someone who is: intelligent, self-sufficient, pleasant, flexible, charming, compulsive, detail-oriented and extremely well-organized. Although medical knowledge would be a plus, it is more easily acquired than the other qualities (especially because other medical personnel already on staff can serve as a source of this knowledge). A coordinator is sometimes referred to as a jack-of-all-trades because research permeates all areas of a practice (i.e., marketing, billing, scheduling, patient relations and interaction, facilities, and operations and processes.)1 In a given day, a coordinator may wear all of these hats, in addition to general research duties, which include: scouring patient charts for study candidates, patient recruitment, patient follow-up, consenting, data gathering and recording, specimen collection, managing and scheduling patient visits, monitoring visits, and other study meetings.
In addition to the principal investigator and study coordinator, a site may also have sub-investigators. These generally include other physicians, medical staff, lab personnel, and any others who will play a role in the completion of a clinical trial. All study personnel must complete important training prior to being able to be eligible to conduct clinical research. The FDA requires that all research staff complete good clinical practice (GCP) training. GCP is an ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve human participants. Compliance provides public assurance that the rights, safety, and well-being of trial participants are protected.4 Our research staff completed GCP training via an online course provided by the National Institute of Health. Many times a course such as this will be sufficient proof of GCP training, however there are some sponsors that require completion of a specific GCP training and certification prior to initiating a study site. In the case of the protection of human participants, one can never be too careful and have too much training, as the protection of human rights and their safety is paramount. In addition, research staff will also need a thorough understanding of the principles of conducting clinical trials, including their ethical and regulatory requirements.
Developing a Research Infrastructure
In addition to completing the necessary training to become a clinical research investigator, physicians must also consider how to build the proper infrastructure to be successful at clinical research. Clinical research tends to be most successful when it is integrated into the overall workflow of the practice, which requires the collaborative efforts of many different departments, including:
- Marketing: Develop advertisements and recruitment materials, help with recruitment strategies, obtain referrals, post information about your research, direct people to web site, make flyers and brochures to give patients3
- Billing: Assist in identifying all clinical trial costs, determine and designate standard-of-care costs vs. sponsor-paid costs, identification and documentation of research participant and services, linking research charges to research study account, budget development3
- Patient concierge: Schedule patients for study screenings and follow-up visits, answer patient questions and concerns, work to obtain patient records
- Facilities & Information Technology: Ensure your site has necessary research equipment, storage, archive space, secure data management servers
- Operations & clinic processes: Integrate clinical trial protocol into existing workflow across all facets of patient visits in clinic
It is often necessary to create separate billing and scheduling for study patients to ensure you are extremely careful not double dip (e.g., being paid for research visits by clinical trial sponsor and also charging patients for the same visit).
Once you’ve established the infrastructure needed to accommodate your first clinical trial it becomes much easier to do future trials. The first trial for which you are a principal investigator will come with a steep learning curve (depending on the type of trial), but that will pay off with future studies. If a sponsor believes you have the infrastructure and patient population to meet study criteria they will schedule a pre-study site qualification visit. During this visit a representative from the sponsor, and possibly the CRO they are working with, will visit your practice to determine if your site is qualified to participate in the trial. They will likely review the original site information survey that assesses your patient population, equipment on-site for research purposes, infrastructure you have in place, personnel to work on the trial, and overall space needed to comply with the study protocol.
At this point you will probably not have access to the study protocol, but you can still establish a majority of the research infrastructure. If you are selected as a site you will then receive the study protocol. At that time you will want to make it a priority to modify your current workflow and operations to meet the study obligations defined in the protocol. One way to make a great first impression to the sponsor is to show that your practice is prepared to conduct research by having study equipment already purchased and setup. Some common research equipment that applies to almost all clinical trials includes1,5:
- Personnel: An MD to serve as principal investigator, a dedicated study coordinator, and any additional staff that will serve as sub-investigators
- Workspace for study coordinator and study monitor (when they visit to review completed case report forms)
- An institutional review board (IRB): Committee designated to protect the rights, safety, and well-being of participants in a clinical trial; either a local IRB (at the study site or within a couple miles) or a central IRB (a commercial IRB that provides services for multiple sites) may be used
- Internet access and e-mail capability
- Fax machine
- Storage facilities (usually shelving, drawers, and locked cabinets) for housing:
- Case report forms (CRFS)
- Study drug or investigational agent
- Extraneous materials for specific study (e.g., liquid nitrogen dewar, centrifuge, urine drug screen cups)
- A pharmacist, phlebotomist, and lab, radiology, or other technical support depending on specifics of protocol (some sponsors permit the use of external labs as long as they are accredited and listed on the appropriate regulatory documents)
Completing the necessary formalities
Shortly after the site qualification visit you will be notified whether or not your practice was selected as a research site. If selected, you will need to complete the remaining regulatory documents, including FDA form 1572, which is a federal form that declares the investigator will abide by federal regulations regarding the use of drugs in an investigational setting, CVs, medical licenses, and GCP training certificates, to name just a few.
You will also receive a clinical trial agreement (CTA), the study protocol, and a budget for review and approval. The protocol specifies your duties and obligations during the trial. Medscape.com provides a set of nine questions to consider when evaluating a protocol and determining if the trial is right for your practice:
- Is the protocol scientifically sound and does it have merit?
- Do you have the staff and equipment to complete the protocol requirements?
- Do you have the study population, or can you get the study population referred from other doctors?
- Is the budget adequate, the contract acceptable?
- Do you have the time to devote to trial oversight, attending meetings and meeting with study monitors (from the CRO)?
- Does it affect your regular practice operations? If so, can you integrate the protocol into your current workflow?
- Who will manage the billing? Who will set up the research billing to avoid “double dipping”?
- Who handles data quality and integrity, data management, and study findings?
- How will you market the site to existing and potential new patients?
If you approve the CTA, budget, and protocol and agree to become a study site you will have to obtain IRB approval and prepare for a site initiation visit. Usually the CRO will take the practice information you have given them and submit the IRB application on your behalf. There are other instances in which you will have to prepare an IRB application and submit it to a local or central IRB for approval. Fortunately, all of the study documents will have already been created for you by the study sponsor so you will only have to complete the IRB application for your site.
The final steps……to getting started
The last step before actual recruitment and enrollment of participants is the site initiation visit. Usually a CRA from the sponsor’s CRO will conduct this visit. During the SIV, a CRA will provide a detailed tour of the study protocol and discuss all necessary study procedures, including the screening process, enrollment, randomization and treatment assignment, data capture using CRFS (or ECRFs if done electronically), follow-up visits, adverse events, and study termination. The SIV can last several hours and normally the study coordinator is required to be present for the entire meeting. The principal investigator will also be required to attend a portion of the meeting. The overall purpose of the SIV is to provide complete study training to ensure that you and your site are completely prepared to complete all study procedures.
Following the SIV your practice’s focus should be on recruiting and enrolling as many patients as possible that meet study criteria. Nearly 80% of trials fail because of an inadequate number of patients, so when you are trying to land clinical trials for your site your primary selling point should be your ability to populate the study – but make sure you can back up your promises.6 Meeting your target enrollment goal is the best way to insure your site is selected for future clinical trials.
Establishing all the components of a clinical research program can be daunting, as it takes significant time and start-up costs. Consider it like any other investment – be smart about selecting trials, be diligent in your review of the protocol and CTA, adequately prepare your practice and staff, and closely monitor the day-to-day operations of the research so you can prosper in the long run. A successful clinical research program can result in numerous achievements for you and your practice, including7:
- Professional development
- Be at the forefront of new pain management treatments
- Develop research partnerships and collaboration with other physicians
- Work with investigational medications and products
- Professional recognition (often contingent on number of patients enrolled in study)
- Present research at national conferences
- Speak at conferences and other educational events
- Co-author papers
- Earn continuing education credits
- Help design future protocols
- Be seen as a leader within field by assisting in the development of breakthrough drugs and treatments
- Personal satisfaction
- Offer patients treatments that may not be available elsewhere
- Play a pivotal role in the advancement of pain management by helping establish new medicines and medical devices
- New revenue stream
- Receive compensation from sponsors for successfully conducting clinical trials through enrollment of participants and completion of follow-up visits
- Properly executed studies can net practices as much as $58000 in revenue, with net income as much as 40%.6
Although beginning a clinical research program will take a lot of time and effort, if executed properly it can be an extremely rewarding endeavor. Clinical trials are at the heart of all medical advances. Carefully conducted, quality clinical trials are the world standard for identifying and developing the best possible methods to prevent, detect, and treat medical conditions and diseases, as well as develop new medical devices and procedures. These trials have the potential to change the course of pain management and the lives of patients suffering from chronic pain. In becoming an active clinical researcher you put yourself and your practice at the forefront of a rapidly advancing field that you can help shape.
Dr. McJunkin and Dr. Lynch founded Arizona Pain Specialists, a comprehensive pain management practice with three locations, seven pain physicians, ten midlevel providers, three chiropractors, on-site research, and behavioral therapy. They teach nationally and are consultants for St. Jude Medical and Stryker Interventional Spine. Through their partner company, Boost Medical, they provide practice management and consulting services to other pain doctors throughout the country. For more information, visit ArizonaPain.com and BoostMedical.com.
Trudy Madan, MHA, is the CEO and Sheri Campbell is the VP of Marketing and Operations for Synergyst Research. Synergyst Research contracts with physicians to assist with administrative duties and increase clinical research studies. In 2011, Synergyst Research negotiated more than 150 research studies in all specialties. Discovery Clinical Trials partners with physicians to create research centers within private practices. As of 2011, Discovery Clinical Trials created 19 research center partnerships with physicians across the United States. Please visit us online at www.synergystresearch.net and www.discoverytrials.com . For more information, email firstname.lastname@example.org or call 210-447-2080.
- Stone, J. (2010). Conducting clinical research: A practical guide for physicians, nurses, study coordinators, and investigators (2nd Ed.). Mountainside MD Press: Cumberland, MD.
- FDA. “Investigational New Drug Application.”
- Arimendy, C. How to start doing office-based clinical trials. June 09, 2010. www.medscape.com/viewarticle720916. Accessed January 26, 2012.
- Guideline for good clinical practice. www.ichgcp.net. Accessed January 27, 2012.
- Ginsberg, D. (2009). Becoming a successful clinical research investigator (2nd Ed.). CenterWatch: Boston, MA.
- Rollins, G. Physicians find clinical research brings income and treatment options. August 1, 2002. www. sendemissary.com/Focus-on-Clinical-Investigators-Coordinators/clinical-research-benefits-for-physicians.html. Accessed January 24, 2012.
- Clinicaltrials.com Knowledge Center. www.clinicaltrials.com/knowledge_center/?faq_category=Investigators#. Accessed January 24, 2012.