- Email: [email protected]
Conducting Research in an Office Endovascular Center
CHAPTER 38
Conducting Research in an Office Endovascular Center LAURA D. BAULER, PHD
Research is essential to the success of the office-based endovascular center (OEC) because research solves problems. Without research the safety and efficacy of procedures performed in an OEC will not be proven, and these data provide the evidence needed to convince the Centers for Medicare and Medicaid Services (CMS) and insurance companies to continue to reimburse and expand the number of procedures that can be performed in an OEC. Quality improvement research allows you to track the success of your OEC and identify areas in your practice that could be improved upon. Both success rates and continued improvement of your practice will correlate directly to the recruitment and retention of patients. For clinicians who are associated with a medical school, research provides an opportunity to mentor students and residents, as well as advance your academic career. Most importantly, research is the key to advance the field of endovascular medicine, by testing new techniques, medications, and equipment, to identify tools that can be used to improve the health of patients. Research develops the evidence needed for evidencebased medicine. Currently, the field of translational medicine, which moves research from the bench to the bedside, is rapidly growing. Basic scientists identify a multitude of treatments that could benefit patients; however, they do not have the clinical knowledge and expertise needed to transition those treatments to the bedside. As few as one in five basic research discoveries lead to a clinical trial.1 By partnering with academic institutions, an OEC can provide a venue to bridge basic science research into the clinic. This chapter will provide the foundational knowledge needed to initiate medical research from developing a research question to publishing the findings. Aspects such as defining a study team, project design, literature searches, regulatory oversight, and resources will also be addressed. When initiating research for
the first time, we strongly advise identifying a mentor who can guide, train, and advise you as you develop your research project. However, even seasoned investigators should consider identifying collaborators who have expertise in areas beneficial to the project.
RESEARCH PROCESS The strength of our knowledge depends upon the quality of the research that supports it. Research is a systematic process that starts with a question. The question is answered by a carefully designed study with appropriate controls to ensure the answer is valid. The best studies build off the work of others to expand the knowledge of the field; a literature review is key in identifying this foundational knowledge. Recruitment of a study team will enable the work to be dispersed and provides the expertise needed for each component. The project protocol should be designed using the most appropriate methodology to accurately answer the research question. For any project involving human participants or data, the study must be approved by an institutional review board (IRB) to ensure the protection of the rights and safety of participants. After IRB approval the data collection can begin, followed by data analysis, and presentation of the results. This process is outlined in Fig. 38.1.
RESEARCH QUESTIONS The research process starts with a problem that forces you to begin asking questions. This may involve an aspect of medicine that does not make sense or a problem within the OEC practice itself that cannot be answered without collecting data. A research question guides a project like a map, directing what information needs to be obtained to answer the question. If the question is too broad or vague, the study will be
Office-Based Endovascular Centers. https://doi.org/10.1016/B978-0-323-67969-5.00038-1 Copyright © 2020 Elsevier Inc. All rights reserved.
315
316
SECTION VII
Other Important Considerations
Research Queson Development Presentaon of Findings
Study Team Recruitment
Literature Review
Data Analysis
Data Collecon
Study Design
Regulatory Review (IRB)
FIG. 38.1 The research process.
equally ambiguous and difficult to address; much like trying to use a map of the United States to direct patients to the location of your OEC. There are two types of questions, research questions and regular questions. A regular question can be easily answered, the information is already available, it just may take a bit of searching to find. A research question on the other hand has an answer that is unknown; it is a novel question that, when answered, will provide additional knowledge to the field. Good research starts with unanswered questions triggered by a curiosity that cannot be satisfied with a thorough literature search. The development of a solid research question requires knowledge of the field. Initial questions are commonly generated during the practice of evidencebased medicine following a literature search that reveals insufficient evidence to address the question. Conferences, field-specific journals, and conversations with colleagues can also serve as a source of questions. Above all, the researcher must be interested in the answer to the question; without this investment, the project will not be propelled forward.2 For research
TABLE 38.1
Good Research Question Characteristics. 1. Addresses a Problem 2. The answer is unknown 3. Topic is interesting and significant 4. Specific enough to be answered
in an OEC, an important factor to consider is the feasibility of the question; can it be addressed by investigating the patients in your practice, with data from a registry that you participate in, or by collaborating on projects initiated by other centers. The best research questions are very specific and significant. If we think back to the map analogy, good research questions are focused or “zoomed in” to the street level of your city, this provides a much better guide to reach your destination. The answer to the question should be significant, meaning that the problem that you are faced with needs to be solved. To publish, the problem and solution must be relevant and important to physicians and scientists beyond your practice. One method of developing a clinical research question is based upon the acronym PICO, which stands for patient/problem, intervention, control/comparison group, and outcome.3 The PICO method, commonly used in evidence-based medicine to guide development of a targeted literature search, provides a research question that is specific and answerable. It also enables easy searching of the literature to identify what studies have already been completed, and what questions are left unanswered. Regardless of the method used to develop your question, a good research question guides the project and has been developed with the desired outcomes in mind (Table 38.1).
THE STUDY TEAM Following the development of a good research question, a study team should be recruited to conduct and support the research. The principal investigator is in charge of the project and responsible for recruiting the study team. Team members may include colleagues and collaborators, mentees (residents and medical students), and research support personnel. Principal investigator (PI): The principal investigator is responsible for guiding the research team,
CHAPTER 38
Conducting Research in an Office Endovascular Center
providing research expertise, topic-specific knowledge, and funding the project. Ultimately the PI is responsible for all aspects of the project. In order to conduct research and successfully complete the project, someone must lead the project and direct the team. Project manager: The project manager is responsible for coordinating all aspects of a project including personnel, timelines, resources, and budget. This team member is often the “second-in-command” and can move the project forward when the PI is busy with other roles. A project manager can manage several projects at once but would need to have protected time dedicated to the project. This job may fall to an office manager, administrative staff within the OEC, or the PI. Due to the time and effort required to direct a research project, having the PI also be the project manager is not ideal. Information technology/electronic health record (EHR) personnel: These personnel are responsible for mining the EHR to obtain the data needed to answer the question. They may also be involved in ensuring that any patient personal identifying information (PII) is safely protected. A full-time individual in this role is likely not required; another member of the team may fulfill this role including an office manager, administrative staff, residents, or students. Research coordinator: This member is responsible for patient recruitment, documentation, and compliance with the clinical protocol. A research coordinator is especially important for participation in a clinical trial; however, a project manager may also fill this role. The need for a research coordinator depends upon the size and nature of the project, as well as the PI’s ability to dedicate time to research. For a retrospective study examining OEC patient records, this role is likely not needed. Data managers: This member of the team assembles the data collection tools and ensures the data are accurate, carefully documented, organized, and stored appropriately. They often work closely with the statisticians. A data manager is not a required role, as other team members may fulfill these tasks. Statisticians: For a clinical research project, a statistician is essential. They contribute several important components to the study, including determining the sample size needed to adequately power the study, determining which statistical tests are required to answer the research question, and performing the final analysis. There are multiple options for statistical support: (1) collaborate or hire a statistician, (2) recruit a team member with appropriate statistical knowledge, (3) obtain the necessary training for personnel to fulfill this role.
317
Medical librarian: A medical librarian can assist with the literature search to ensure that all relevant literature is identified. They provide knowledge of keywords and databases available as well as access to the medical literature. While not a required team member, a literature search is extremely important aspect of research to ensure that the project is novel and will add new knowledge to the field. Medical editor: This member provides knowledge of the publication process and editorial guidance on disseminating the project findings. They may identify journals as well as help with writing and revising the manuscript. They may also serve as a peer-reviewer of any manuscripts and abstracts that are generated. A formal medical editor is certainly not required to be a team member, a colleague with scholarly expertise and willingness to help would suffice. Residents and student trainees: A trainee can fulfill almost any role within the project other than the PI. Mentoring a trainee during a research project can also have benefits for the mentor and project. Trainees are often very motivated and bring new ideas to the project. Trainees can also provide assistance with any aspect of the project, lightening the load of a research project from senior team members and increasing the productivity of the team.4 Participation in research is a good learning opportunity for trainees who may want to pursue research in their future careers.5 It helps to build their CVs with research experiences, presentations, and publications. Research also provides trainees with an opportunity to learn more about the specialty while gaining experience and insight about the medical field. Research also provides trainees with an opportunity to collaborate with mentors and colleagues, they may call upon for support of their future careers with recommendation letters or connections. While a trainee is not a required part of a research project, trainees are often extremely useful members of the team.
LITERATURE REVIEW To develop a good specific research question, you need to have a thorough understanding of the current knowledge in the field: what research has been conducted, what is known, and what questions still remain. While the literature search typically comes after an initial research question has been developed, it serves to further shape and refine the research question into a specific and significant question. The literature review should be comprehensive, identifying all possible literature that has been conducted on a topic so that the research team can become experts in the field and
318
SECTION VII
Other Important Considerations
identify the gap in the literature that could be addressed by their research. For an OEC, physicians may not have ready access to the literature; obtaining privileges at a local hospital that has a library, collaborating with colleagues at an academic institution, or partnering with an academic institution as community or adjunct faculty member can provide access to the medical literature. A number of databases are available to identify medical literature including PubMed, CINAHL, Scopus, Embase, Google Scholar, or the Web of Science. These databases can be searched by keyword, subject, or author to identify relevant literature. Developing a search string to identify relevant literature may help you focus your results. As discussed above, PICO is a common tool used to generate a patient-centered medical search string (Fig. 38.2).6 As an example, if you were interested in determining what factors put patients with critical limb ischemia undergoing an endovascular intervention at risk for bleeding, you may use the following PICO keywords: P: critical limb ischemia, I: endovascular, O: bleeding. The C: comparison/control is often difficult to determine before the literature search, as you may not
know what control group was used in a particular study. While a PICO-based search string will provide focused results, it will be limited by the search terms used, thus may not be entirely encompassing of all relevant literature. Relevant literature may be found through a variety of means including multiple searches with different keywords, similar articles recommended by the search tool, from the reference list of key papers, or from manuscripts that have cited your key articles.
DESIGN OF THE STUDY AND RESEARCH PLAN The design of the study is critical in determining the value of the research. A well-designed study is constructed in a manner that avoids all possible bias, and controls for as many factors as possible, to ensure the conclusions drawn from the data are valid. It is best to consult with a statistician during the study design phase to determine the sample size and ensure that the data collected can be analyzed in a manner that addresses the research question. A vitally important aspect of a research study is the control group, as without appropriate controls you cannot determine with any
Populaon/Problem
Intervenon
Control/Comparison
Outcome
FIG. 38.2 PICO question components.
CHAPTER 38
Conducting Research in an Office Endovascular Center
certainty that a particular variable had an impact on the outcome. For clinical research the gold standard study type is a randomized controlled trial (RCT); however, this type of study is not always feasible or appropriate to address the research question. Clinical research can be divided into two categories: experimental research or observational research (Fig. 38.3). Experimental research involves the direct testing of a hypothesis or intervention, while observational research involves examination of the natural features of a study group without direct intervention.7 The best study design is determined by the research question and the desired outcomes of the project. Each study design has strengths and weaknesses that should be considered.
Experimental Research Experimental or interventional studies are often prospective and are designed to evaluate the direct impacts of a treatment on a specific disease outcome.
Randomized controlled trial (RCT): RCTs are the gold standard of clinical research; because of their design these studies can provide evidence for a causal relationship between an intervention and an outcome.8 Due to the careful enrollment of participants who are randomly assigned into the control or experimental group, the only anticipated difference between these groups is the intervention.7 These types of studies are extremely expensive, and recruitment is restricted resulting in problematic generalizability. For some studies, it would be unethical to conduct an RCT because when treatments are shown to improve the health of patients, it becomes unethical to maintain a control group. This is especially problematic for surgical interventions, as randomizing patients to a control group may result in irreparable consequences. Quasi-experimental, pre-/poststudy or nonrandomized controlled trial: These trials are similar to RCTs, in that an intervention is tested in one group and compared with another group. In the absence of the randomization, these studies may lack internal validity, in that
Clinical Research
Experimental Research
319
Observaonal Research
Prospecve
Retrospecve
Randomized Controlled Trial
Case Controlled
Case Controlled
Quasi-Experimental Non-randomized trial
Cohort
Cohort
Cross over Study
Cross-seconal
Cross-seconal Case Series/Case report
FIG. 38.3 Categories of research study design.
320
SECTION VII
Other Important Considerations
the treatment and control groups may not be comparable at baseline. Some of these biases can be overcome with careful statistical analysis, but others may not be overcome and may limit the generalizability of the results. Studies can be designed as single arm, which uses the same participant population as control and experimental subjects (as with pre-post studies), or as multiple arms where different groups are compared with each other.7 Crossover study: A crossover study is a type of interventional study where the study participants serve as both control and experimental group at different times during the study. Subjects are initially treated as experimental or control group in phase one, followed by a washout period where the treatment is stopped, and then in phase two the groups are swapped into the other condition. This crossover design demonstrates reversibility of a treatment and compensates for unsuccessful randomization, as subjects now become their own controls.7
Observational Research Observational research studies examine the study and control groups to determine if they have different outcomes or risk factors that may be causal in determining those outcomes. Observational research can be prospective or retrospective depending upon the order of events within the project. When the project is designed first, and data collection follows, this is termed prospective. When the data have already been collected, as is the case of an EHR or registry, followed by development of a research question and study design, then the study is retrospective. Cohort study: Cohort studies are used to determine the incidence rate and natural history of a disease. A study population or cohort with a unique set of characteristics is defined and then followed the over time to determine if a certain outcome develops. Multiple outcomes and exposure variables can be studied in the same population. Prospective cohort studies are often inefficient, as it may take a long time for the outcome to occur, and during that time participant dropout often occurs. However, cohort study data can be examined retrospectively to answer new questions. Case-control study: The purpose of a case-controlled study is to determine the relative importance of specific factors in impacting an outcome.9 These studies are typically conducted retrospectively, and participants are identified based upon the outcome of interest, and then matched with a control group who does not have the outcome.8 This is a good study design if you are studying outcomes that are rare, but suffers from
sampling bias in that you cannot control the selection of participants in your dataset. This type of study works well for secondary data analysis, such as that obtained from the EMR, and can be used to determine the relative odds of a certain surgical outcome such as mortality, 30day readmission, or bleeding complication following a particular surgical intervention. Cross-sectional study: Cross-sectional studies are used to determine prevalence of a specific outcome and exposure status simultaneously in a population.8,9 Determining the prevalence of an outcome allows the physician to determine the likelihood of a particular diagnosis for a particular patient. These studies can be done prospectively or retrospectively, and their accuracy depends upon careful study group selection to avoid biasing the results. For an OEC, a cross-sectional study would be a good starting point to identify the baseline prevalence of certain conditions within your patient population that could be used as a basis for further intervention and research. This type of study is also useful for measuring the impact of quality improvement studies pre- and postintervention. Case report or case series: A case report or series is a description of a disease process in a single individual or several subjects without a control group. The cases described are typically a variation from what is commonly seen in a disease, including unique presentation of disease, novel patient populations, or adverse consequences of treatment. Case reports are often the first report to identify a new disease or adverse health effect. These types of reports are fast, easy, and inexpensive. Describing several cases simultaneously with similar features increases the evidence available to support a hypothesis, but without a control group you cannot provide conclusive evidence to support or refute a hypothesis.
Quality Improvement Quality improvement is a type of research that is focused on improving the processes within an organization to improve the quality, cost, and value of the care provided. The work is often focused on targeting a triple aim, with the goals of improving (1) the health of a community, (2) reducing the cost of medical care, and (3) improving the population’s experience within the healthcare system.10 With these goals in mind, there are many projects within an OEC that could be targeted, such as reducing cost of procedures for patients and the practice, improving the health outcomes of the community based upon preventative care, and improving the patient care experience while being treated at the OEC. Successful QI projects have a champion directing
CHAPTER 38
Conducting Research in an Office Endovascular Center
the project, who is invested in the outcomes. Thus, allowing operators or staff to identify areas they want to improve increases the success of QI projects. These concepts and methodology used in quality improvement are expanded further in Chapter 13.
Clinical Trials Clinical trials provide the evidence needed by the Food and Drug Administration (FDA) to evaluate the benefits and risks of a new medication or medical treatment to determine if it is safe for patients. In order to obtain the necessary data, thousands of patients are enrolled in clinical trials, many more patients than can reasonably be identified from a single institution. Participation in a clinical trial has several benefits: (1) the patients in your practice may benefit from novel drugs, devices, and treatments currently being studied; (2) the medical protocols within your OEC may change based upon new clinical evidence identified in the clinical trial and; (3) participating in a clinical trial is a good way to develop research experience and skills.11 Clinicians who have participated in clinical trials have also indicated that their clinic processes improved based upon documentation efforts required for the clinical trial, and that the profile of their practice has increased.11 A list of clinical trials currently being conducted can be found on the NIH website https://clinicaltrials.gov.
321
The Healthcare Cost and Utilization Project (HCUP): A repository of longitudinal statewide inpatient data. HCUP is the largest collection of hospital care data in the United States that includes all payers, encounterlevel data from 1988 to present.13 HCUP consists of several different databases including the National Inpatient Sample (NIS), the State Inpatient Database (SID), and the State Ambulatory Surgery and Services Databases (SASD). American College of Surgeons National Surgical Quality Improvement Program (ASC-NSQIP): A nationally validated, risk-adjusted, outcomes-based dataset that contains more than 28,000 cases with as many as 134 data points per patient tracked for 30 days after their operation. Currently, more than 710 individual hospitals have enrolled in this registry.14 Society of Vascular Surgery, Vascular Quality Initiative (VQI), and Patient Safety Organization (SVS-PSO): An aggregation and analysis of clinical data for patients undergoing specific vascular treatments designed to improve the quality, safety, effectiveness, and cost of vascular healthcare. Reports are generated twice per year to show trends, volume, process characteristics, and inhospital outcomes. The VQI consists of 12 registries with outcomes from more than 500,000 vascular procedures performed across the United States and Canada.15 Centers that participate in the VQI can compare their performance with region and national benchmarks.
Postmarket Studies Postmarket studies are studies conducted after the FDA has approved a product for marketing. They are typically sponsored studies that serve to collect additional information about a product’s safety, efficacy, and optimal use.12 These may include RCTs, drug interaction studies, efficacy studies, pharmacokinetic and pharmacodynamic studies, or pediatric trials. Some device companies pay for data to be collected if the OEC is a participant in a national registry.
RESEARCH RESOURCES Databases and Registries Beyond conducting research using the medical records or patients within your own practice, a number of resources exist that can be utilized for research including databases and patient registries (see also Chapter 19). Clinical registries have increasingly been generated from existing practice data for use as patient safety improvement tools, but can also be used as an observational database to address clinical research questions.
Medical Societies Numerous medical societies exist that may serve to foster research in the field. They provide an environment for researchers to identify mentors and collaborators, discuss the latest advancements in clinical research, promote discussions that stimulate research questions, or may provide registries or grants to further research. Relevant societies include the Society for Vascular Surgery, the Society for Vascular Medicine, the Society for Vascular Ultrasound, the Vascular and Endovascular Surgery Society, the International Society of Endovascular Specialists, American College of Cardiologists, Society of Interventional Radiology, and the Outpatient Endovascular and Interventional Society.
Practice-Based Research Networks Practice-based research networks (PBRN) are collaborations between clinical practice and academia designed to foster research.16 PBRNs connect healthcare to research by providing support to clinicians throughout the research process. These networks serve to help clinicians develop specific impactful research questions,
322
SECTION VII
Other Important Considerations
design and conduct studies, analyze data, and translate knowledge into practice. The PBRN network serves to better care for patients by conducting research in a patient population more representative of the general public, including patients with multiple comorbidities who are often excluded from RCTs. Additionally some diseases are only treated in certain settings making these topics more likely to be under represented in research studies.
Grants and Contracts For more extensive research projects, the project may require funding support to pay for personnel, resources, or services. The National Institute of Health is the leading funding resource for medical research in the United States, supporting more than 44,000 research projects in 2017.17 Starting in 2012, the National Center for Advancing Translational Sciences (NCATS) was established to fund translational research projects. Funding support for PBRNs can come from the Agency for Health Care Research and Quality (AHRQ). Funding may also come from local initiatives or societies as mentioned above. Many academic hospitals have award mechanisms that support the development of translational research or clinical trials. There are also nonprofit foundations, like the Kellogg Foundation, that support clinical research.
Regulations To ensure patient consent and understanding of the research, an informed consent document is an important part of any research project. For research studies that involve human subjects there are a number of ethical considerations that need to be accounted for before the research is initiated, including review of the research protocol by an institutional review board (IRB). If the OEC does not have access to the local IRB at an academic institution, there are regional IRBs that can be utilized to get project approval. Data obtained from medical records can be analyzed without informed consent as long as the findings of the project will not be published. For researchers interested in conducting quality improvement studies, this eases the burden of this hurdle, as long as they only report on the process utilized for improvement instead of the patient outcomes from the pre-post measures of their research.18 Institutional Review Board (IRB): The IRB is an ethical research committee, responsible for protecting the rights, welfare, and well-being of human research subjects.19 Most academic institutions have an IRB, which is responsible for reviewing research protocols to ensure
that the human subjects who will be asked to participate in that research are properly protected. Several factors are taken into consideration including the autonomy of the subject (their ability to opt in or out of the study), equitable selection of subjects, and the risk-benefits ratio of the study. Autonomy and consent are two of the cornerstone values in research ethics. The Declaration of Helsinki states that research “participants should be treated as autonomous beings capable of making an informed decision whether to participate in research.”20 In the case of database/EHR analysis at an OEC, individual patient consent can be obtained in their initial onboarding paperwork, or may be waived during the IRB review process if the research is determined to be of minimal risk to patients. The riskbenefit analysis helps the IRB determine how much risk the subjects will be exposed to in order to participate in the research, and what benefits will result from the study. The IRB reviews the research protocol including the scientific background of the project, rationale, objectives of the study, the study design, subject population (inclusion and exclusion criteria), subject recruitment, statistical analysis, expected results, study timeline, benefit and risk evaluation, dissemination plans, and any patient consent forms, surveys, or data collection forms that will be used in the study. Ethical considerations: Of recent concern is the involvement of physicians in clinical trials, as they and their patients may both benefit financially from enrolling in the research. Patients can benefit from enrolling in clinical trials through limited financial compensation and receipt of free healthcare. Financial incentives are one of the most important factors motivating physician involvement in research.21 Physicians are tasked with putting the concerns of their patient first above their own benefit, thus any incentives they receive must not influence their regard for their patients best interest.22 The IRB protocol should include measures that will be taken to avoid bias or influence of any financial incentives to study participation.
DATA COLLECTION Study Population The degree that the study population accurately represents the overall population of patients suffering from a disease or variable of interest determines the value and generalizability of the results. In the ideal situation, the characteristics of the study sample will directly match the overall population. Random sampling is the simplest method to match populations; however, depending upon the source of your study participants
CHAPTER 38
Conducting Research in an Office Endovascular Center
the study may already be biased, thus you may need to carefully design your study sampling method to account for these biases as much as possible. Careful consideration of all the variables that may impact your outcome, and devising methods to overcome these hurdles, will ensure selection of a study population that best represents the general population.
Sample Size The size of the study population should be predicted before the study begins. A statistician can use preexisting data about the outcome to help predict how many subjects need to be enrolled to adequately power the statistical analysis. Enrolling more subjects than is needed is costly and adds difficulty to the research project, but enrolling too few may mean the study fails to detect relationships that exist between variables and outcomes, and inadequately addresses the research question.23 A statistical power analysis will determine the probability that the study can identify relationships that exist in the data.
Data Collection Tools Care should be taken during the data collection phase to ensure that the data are accurate, complete, and organized. Missing values or duplication of records can cause problems down the road. A number of tools exist that can support the data collection process. For studies utilizing data in an EHR, the data can be obtained from an information technologist who can export a certain dataset with the variables of interest. However, not all EHRs are designed for research, thus the data may need to be abstracted from the medical record by study team members. Above all, the researchers must ensure that the subjects in their study are protected, this means developing a data management plan to protect any PII. Data may be collected into a simple password-protected database or into a tool designed for research data collection such as REDCap (Research Electronic Data Capture).24 REDCap is a HIPAA-compliant data collection tool that enables academic researchers to develop surveys or data collection instruments.
DATA ANALYSIS Analysis of the data is the most exciting aspect of the study, as you can finally begin to answer your question. With most medical questions the answer is rarely black or white, instead we are asking about the probability that a variable impacts an outcome. Statistics allows us to measure these probabilities. To get an accurate answer to the research question, an expert, typically a
323
statistician, should conduct the analysis. Utilizing the appropriate data analysis method depends on the study design, variables collected, and desired outcome. Data analysis tools should be identified in the design phase of the study.
PRESENTING YOUR FINDINGS
Research findings should be disseminated beyond your group to maximize the benefits of conducting a project. Publication is the ultimate goal, creating a permanent record of the research and its findings. The work can also be disseminated at local, regional, or national conferences by submitting an abstract for presentation in a poster or oral format. While clinical research studies have clear value, quality improvement studies describing the process of improvement utilized to achieve your goals can also be published and are valuable to other groups who are attempting similar initiatives for improvement. To ease the burden of the presentation process, collaboration with an academic colleague or with a medical writer or editor can help by providing knowledge of the publication process.
PARTNERING WITH A MEDICAL SCHOOL For many of the topics discussed above, access to resources and individuals who can collaborate on your project can be facilitated through partnering with a medical school. You can gain access to a number or resources including the library, students and residents, grants management, statisticians, medical editors, management of industry contracts, and colleagues. Due to the complexity and regulations surrounding a clinical trial, medical schools often have entire departments dedicated to ensuring compliance with FDA regulations.25 Partnering with the medical school may be done through collaborations with medical school faculty or by joining a medical school as community faculty. At most medical schools, community faculty are volunteers who contribute to education, research, community engagement, and committees at the medical school. In return, community faculty gain access to the medical school resources described above in addition to opportunities for continuing education. For many medical schools their required commitment is minimal, often 25e50 h of service per year. For OECs looking to collaborate on research projects, committing to include students and residents on your research projects may satisfy these requirements.
324
SECTION VII
Other Important Considerations
FINAL CONSIDERATIONS Conducting research requires an investment of time, resources, and effort toward a project. As research projects always take more time than anticipated, the research team must be fully invested and interested in the project to dedicate the time needed to move the project forward and successfully accomplish their goals. Numerous students and residents are interested in participating in research, but they often fail to realize the time commitment required. Setting clear expectations of time, investment, and quality is important to make sure the mentor-mentee relationship is built on common ground. Thus careful selection of students or residents is critical to both advance the project and generate a good mentor-mentee relationship that will be mutually beneficial. Similar care should be taken in identifying collaborators that have the needed skills for a project.
CONCLUSION Research is essential to address questions that arise during the practice of medicine. While some questions can easily be addressed with a literature search, true research problems will have unanswerable questions that require research to solve. An OEC has a responsibility to provide the best patient care possible and to do this; research is a necessary aspect of patient care. Through contributing to registries, undertaking quality improvement studies, or answering unanswered questions, physicians of an OEC can make meaningful contributions to improving medical care provided. Not only does this research directly benefit the OEC, but it also can benefit the field of endovascular medicine.
REFERENCES 1. Cripe TP, Thomson B, Boat TF, Williams DA. Promoting translational research in academic health centers: navigating the “roadmap,”. Acad Med. 2005. https://doi.org/ 10.1097/00001888-200511000-00008. 2. Alon U. How to choose a good scientific problem. Mol Cell. 2009;35:726e728. https://doi.org/10.1016/j.molcel.2009. 09.013. 3. Evidence-Based Medicine Resource Guide. Georg. Univ. Dahlgren Meml. Libr.; 2019. 4. Morrison-Beedy D, Aronowitz T, Dyne J, Mkandawire L. Mentoring students and junior faculty in faculty research: a win-win scenario. J Prof Nurs. 2001. https://doi.org/ 10.1053/jpnu.2001.28184. 5. Mabvuure NT. Twelve tips for introducing students to research and publishing: a medical student’s perspective. Med Teach. 2012;34:705e709. https://doi.org/10.3109/ 0142159X.2012.684915.
6. Richardson WS, et al. The well built clinical question: a key to evidence based decisions. ACP J Club. 1995. https:// doi.org/10.7326/ACPJC-1995-123-3-A12. 7. Thiese MS. Observational and interventional study design types; an overview. Biochem Medica. 2014. https://doi.org/ 10.11613/BM.2014.022. 8. Noordzij M, Dekker FW, Zoccali C, Jager KJ. Study designs in clinical research. Nephron Clin Pract. 2009. https:// doi.org/10.1159/000235610. 9. Mann C. Observational research methods. Research design II. Emerg Med J. 2003. https://doi.org/10.1136/emj.20.1.54. 10. Triple Aim for Populations. Inst. Healthc. Improv.; 2019. http://www.ihi.org/Topics/TripleAim/Pages/Overview.aspx. 11. Batchelor JM, Chapman A, Craig FE, et al. Generating new evidence, improving clinical practice and developing research capacity: the benefits of recruiting to the U.K. Dermatology Clinical Trials Network’s STOP GAP and BLISTER trials. Br J Dermatol. 2017. https://doi.org/ 10.1111/bjd.15959. 12. Postmarketing clinical trials, U.S. Food drug Adm. 2018. 13. HCUP Overview. Healthcare Cost and Utilization Project (HCUP). Agency Healthc. Res. Qual.; 2018. https://www. hcup-us.ahrq.gov/overview.jsp. 14. Ingraham AM, Richards KE, Hall BL, Ko CY. Quality improvement in surgery: the American College of Surgeons national surgical quality improvement program approach. Adv Surg. 2010. https://doi.org/10.1016/j.yasu.2010.05.003. 15. Vascular Quality Initiative, (2019). https://www.vqi.org/. Accessed October 18, 2019. 16. Pirotta M, Temple-Smith M. Practice-based research networks. Aust Fam Physician. 2017;46(10):793e795. 17. RePORT. Funding Facts. Natl. Institutes Heal.; 2018. https://report.nih.gov/fundingfacts/fundingfacts.aspx. 18. Feldman SR. Participating in trials can inform better clinical practice. Br J Dermatol. 2017;177:1148e1149. https://doi.org/10.1111/bjd.15946. 19. Institutional Review Board Guidebook. Off. Hum. Res. Prot.; 2019. 20. World Medical Association. Declaration of Helsinki world medical association declaration of Helsinki. Bull World Heal Organ. 2001. doi:S0042-96862001000400016 [pii]. 21. Rahman S, Majumder A, Shaban S, Rahman N, Ahmed SM, Abdulrahman K, Dsouza UJ. Physician participation in clinical research and trials: issues and approaches. Adv Med Educ Pract. 2011. https://doi.org/10.2147/amep.s14103. 22. Fisher JA. Practicing research ethics: private-sector physicians & pharmaceutical clinical trials. Soc Sci Med. 2008. https://doi.org/10.1016/j.socscimed.2008.02.001. 23. Suresh G, Suresh K, Thomas S. Design, data analysis and sampling techniques for clinical research. Ann Indian Acad Neurol. 2011;14:287. https://doi.org/10.4103/09722327.91951. 24. REDCap: Research Electronic Data Capture, (n.d.). https:// projectredcap.org/about/(accessed March 29, 2019). 25. Arbit HM, Paller MS. A program to provide regulatory support for investigator-initiated clinical research. Acad Med. 2006. https://doi.org/10.1097/00001888200602000-00009.
Conducting Research in an Office Endovascular Center LAURA D. BAULER, PHD
Research is essential to the success of the office-based endovascular center (OEC) because research solves problems. Without research the safety and efficacy of procedures performed in an OEC will not be proven, and these data provide the evidence needed to convince the Centers for Medicare and Medicaid Services (CMS) and insurance companies to continue to reimburse and expand the number of procedures that can be performed in an OEC. Quality improvement research allows you to track the success of your OEC and identify areas in your practice that could be improved upon. Both success rates and continued improvement of your practice will correlate directly to the recruitment and retention of patients. For clinicians who are associated with a medical school, research provides an opportunity to mentor students and residents, as well as advance your academic career. Most importantly, research is the key to advance the field of endovascular medicine, by testing new techniques, medications, and equipment, to identify tools that can be used to improve the health of patients. Research develops the evidence needed for evidencebased medicine. Currently, the field of translational medicine, which moves research from the bench to the bedside, is rapidly growing. Basic scientists identify a multitude of treatments that could benefit patients; however, they do not have the clinical knowledge and expertise needed to transition those treatments to the bedside. As few as one in five basic research discoveries lead to a clinical trial.1 By partnering with academic institutions, an OEC can provide a venue to bridge basic science research into the clinic. This chapter will provide the foundational knowledge needed to initiate medical research from developing a research question to publishing the findings. Aspects such as defining a study team, project design, literature searches, regulatory oversight, and resources will also be addressed. When initiating research for
the first time, we strongly advise identifying a mentor who can guide, train, and advise you as you develop your research project. However, even seasoned investigators should consider identifying collaborators who have expertise in areas beneficial to the project.
RESEARCH PROCESS The strength of our knowledge depends upon the quality of the research that supports it. Research is a systematic process that starts with a question. The question is answered by a carefully designed study with appropriate controls to ensure the answer is valid. The best studies build off the work of others to expand the knowledge of the field; a literature review is key in identifying this foundational knowledge. Recruitment of a study team will enable the work to be dispersed and provides the expertise needed for each component. The project protocol should be designed using the most appropriate methodology to accurately answer the research question. For any project involving human participants or data, the study must be approved by an institutional review board (IRB) to ensure the protection of the rights and safety of participants. After IRB approval the data collection can begin, followed by data analysis, and presentation of the results. This process is outlined in Fig. 38.1.
RESEARCH QUESTIONS The research process starts with a problem that forces you to begin asking questions. This may involve an aspect of medicine that does not make sense or a problem within the OEC practice itself that cannot be answered without collecting data. A research question guides a project like a map, directing what information needs to be obtained to answer the question. If the question is too broad or vague, the study will be
Office-Based Endovascular Centers. https://doi.org/10.1016/B978-0-323-67969-5.00038-1 Copyright © 2020 Elsevier Inc. All rights reserved.
315
316
SECTION VII
Other Important Considerations
Research Queson Development Presentaon of Findings
Study Team Recruitment
Literature Review
Data Analysis
Data Collecon
Study Design
Regulatory Review (IRB)
FIG. 38.1 The research process.
equally ambiguous and difficult to address; much like trying to use a map of the United States to direct patients to the location of your OEC. There are two types of questions, research questions and regular questions. A regular question can be easily answered, the information is already available, it just may take a bit of searching to find. A research question on the other hand has an answer that is unknown; it is a novel question that, when answered, will provide additional knowledge to the field. Good research starts with unanswered questions triggered by a curiosity that cannot be satisfied with a thorough literature search. The development of a solid research question requires knowledge of the field. Initial questions are commonly generated during the practice of evidencebased medicine following a literature search that reveals insufficient evidence to address the question. Conferences, field-specific journals, and conversations with colleagues can also serve as a source of questions. Above all, the researcher must be interested in the answer to the question; without this investment, the project will not be propelled forward.2 For research
TABLE 38.1
Good Research Question Characteristics. 1. Addresses a Problem 2. The answer is unknown 3. Topic is interesting and significant 4. Specific enough to be answered
in an OEC, an important factor to consider is the feasibility of the question; can it be addressed by investigating the patients in your practice, with data from a registry that you participate in, or by collaborating on projects initiated by other centers. The best research questions are very specific and significant. If we think back to the map analogy, good research questions are focused or “zoomed in” to the street level of your city, this provides a much better guide to reach your destination. The answer to the question should be significant, meaning that the problem that you are faced with needs to be solved. To publish, the problem and solution must be relevant and important to physicians and scientists beyond your practice. One method of developing a clinical research question is based upon the acronym PICO, which stands for patient/problem, intervention, control/comparison group, and outcome.3 The PICO method, commonly used in evidence-based medicine to guide development of a targeted literature search, provides a research question that is specific and answerable. It also enables easy searching of the literature to identify what studies have already been completed, and what questions are left unanswered. Regardless of the method used to develop your question, a good research question guides the project and has been developed with the desired outcomes in mind (Table 38.1).
THE STUDY TEAM Following the development of a good research question, a study team should be recruited to conduct and support the research. The principal investigator is in charge of the project and responsible for recruiting the study team. Team members may include colleagues and collaborators, mentees (residents and medical students), and research support personnel. Principal investigator (PI): The principal investigator is responsible for guiding the research team,
CHAPTER 38
Conducting Research in an Office Endovascular Center
providing research expertise, topic-specific knowledge, and funding the project. Ultimately the PI is responsible for all aspects of the project. In order to conduct research and successfully complete the project, someone must lead the project and direct the team. Project manager: The project manager is responsible for coordinating all aspects of a project including personnel, timelines, resources, and budget. This team member is often the “second-in-command” and can move the project forward when the PI is busy with other roles. A project manager can manage several projects at once but would need to have protected time dedicated to the project. This job may fall to an office manager, administrative staff within the OEC, or the PI. Due to the time and effort required to direct a research project, having the PI also be the project manager is not ideal. Information technology/electronic health record (EHR) personnel: These personnel are responsible for mining the EHR to obtain the data needed to answer the question. They may also be involved in ensuring that any patient personal identifying information (PII) is safely protected. A full-time individual in this role is likely not required; another member of the team may fulfill this role including an office manager, administrative staff, residents, or students. Research coordinator: This member is responsible for patient recruitment, documentation, and compliance with the clinical protocol. A research coordinator is especially important for participation in a clinical trial; however, a project manager may also fill this role. The need for a research coordinator depends upon the size and nature of the project, as well as the PI’s ability to dedicate time to research. For a retrospective study examining OEC patient records, this role is likely not needed. Data managers: This member of the team assembles the data collection tools and ensures the data are accurate, carefully documented, organized, and stored appropriately. They often work closely with the statisticians. A data manager is not a required role, as other team members may fulfill these tasks. Statisticians: For a clinical research project, a statistician is essential. They contribute several important components to the study, including determining the sample size needed to adequately power the study, determining which statistical tests are required to answer the research question, and performing the final analysis. There are multiple options for statistical support: (1) collaborate or hire a statistician, (2) recruit a team member with appropriate statistical knowledge, (3) obtain the necessary training for personnel to fulfill this role.
317
Medical librarian: A medical librarian can assist with the literature search to ensure that all relevant literature is identified. They provide knowledge of keywords and databases available as well as access to the medical literature. While not a required team member, a literature search is extremely important aspect of research to ensure that the project is novel and will add new knowledge to the field. Medical editor: This member provides knowledge of the publication process and editorial guidance on disseminating the project findings. They may identify journals as well as help with writing and revising the manuscript. They may also serve as a peer-reviewer of any manuscripts and abstracts that are generated. A formal medical editor is certainly not required to be a team member, a colleague with scholarly expertise and willingness to help would suffice. Residents and student trainees: A trainee can fulfill almost any role within the project other than the PI. Mentoring a trainee during a research project can also have benefits for the mentor and project. Trainees are often very motivated and bring new ideas to the project. Trainees can also provide assistance with any aspect of the project, lightening the load of a research project from senior team members and increasing the productivity of the team.4 Participation in research is a good learning opportunity for trainees who may want to pursue research in their future careers.5 It helps to build their CVs with research experiences, presentations, and publications. Research also provides trainees with an opportunity to learn more about the specialty while gaining experience and insight about the medical field. Research also provides trainees with an opportunity to collaborate with mentors and colleagues, they may call upon for support of their future careers with recommendation letters or connections. While a trainee is not a required part of a research project, trainees are often extremely useful members of the team.
LITERATURE REVIEW To develop a good specific research question, you need to have a thorough understanding of the current knowledge in the field: what research has been conducted, what is known, and what questions still remain. While the literature search typically comes after an initial research question has been developed, it serves to further shape and refine the research question into a specific and significant question. The literature review should be comprehensive, identifying all possible literature that has been conducted on a topic so that the research team can become experts in the field and
318
SECTION VII
Other Important Considerations
identify the gap in the literature that could be addressed by their research. For an OEC, physicians may not have ready access to the literature; obtaining privileges at a local hospital that has a library, collaborating with colleagues at an academic institution, or partnering with an academic institution as community or adjunct faculty member can provide access to the medical literature. A number of databases are available to identify medical literature including PubMed, CINAHL, Scopus, Embase, Google Scholar, or the Web of Science. These databases can be searched by keyword, subject, or author to identify relevant literature. Developing a search string to identify relevant literature may help you focus your results. As discussed above, PICO is a common tool used to generate a patient-centered medical search string (Fig. 38.2).6 As an example, if you were interested in determining what factors put patients with critical limb ischemia undergoing an endovascular intervention at risk for bleeding, you may use the following PICO keywords: P: critical limb ischemia, I: endovascular, O: bleeding. The C: comparison/control is often difficult to determine before the literature search, as you may not
know what control group was used in a particular study. While a PICO-based search string will provide focused results, it will be limited by the search terms used, thus may not be entirely encompassing of all relevant literature. Relevant literature may be found through a variety of means including multiple searches with different keywords, similar articles recommended by the search tool, from the reference list of key papers, or from manuscripts that have cited your key articles.
DESIGN OF THE STUDY AND RESEARCH PLAN The design of the study is critical in determining the value of the research. A well-designed study is constructed in a manner that avoids all possible bias, and controls for as many factors as possible, to ensure the conclusions drawn from the data are valid. It is best to consult with a statistician during the study design phase to determine the sample size and ensure that the data collected can be analyzed in a manner that addresses the research question. A vitally important aspect of a research study is the control group, as without appropriate controls you cannot determine with any
Populaon/Problem
Intervenon
Control/Comparison
Outcome
FIG. 38.2 PICO question components.
CHAPTER 38
Conducting Research in an Office Endovascular Center
certainty that a particular variable had an impact on the outcome. For clinical research the gold standard study type is a randomized controlled trial (RCT); however, this type of study is not always feasible or appropriate to address the research question. Clinical research can be divided into two categories: experimental research or observational research (Fig. 38.3). Experimental research involves the direct testing of a hypothesis or intervention, while observational research involves examination of the natural features of a study group without direct intervention.7 The best study design is determined by the research question and the desired outcomes of the project. Each study design has strengths and weaknesses that should be considered.
Experimental Research Experimental or interventional studies are often prospective and are designed to evaluate the direct impacts of a treatment on a specific disease outcome.
Randomized controlled trial (RCT): RCTs are the gold standard of clinical research; because of their design these studies can provide evidence for a causal relationship between an intervention and an outcome.8 Due to the careful enrollment of participants who are randomly assigned into the control or experimental group, the only anticipated difference between these groups is the intervention.7 These types of studies are extremely expensive, and recruitment is restricted resulting in problematic generalizability. For some studies, it would be unethical to conduct an RCT because when treatments are shown to improve the health of patients, it becomes unethical to maintain a control group. This is especially problematic for surgical interventions, as randomizing patients to a control group may result in irreparable consequences. Quasi-experimental, pre-/poststudy or nonrandomized controlled trial: These trials are similar to RCTs, in that an intervention is tested in one group and compared with another group. In the absence of the randomization, these studies may lack internal validity, in that
Clinical Research
Experimental Research
319
Observaonal Research
Prospecve
Retrospecve
Randomized Controlled Trial
Case Controlled
Case Controlled
Quasi-Experimental Non-randomized trial
Cohort
Cohort
Cross over Study
Cross-seconal
Cross-seconal Case Series/Case report
FIG. 38.3 Categories of research study design.
320
SECTION VII
Other Important Considerations
the treatment and control groups may not be comparable at baseline. Some of these biases can be overcome with careful statistical analysis, but others may not be overcome and may limit the generalizability of the results. Studies can be designed as single arm, which uses the same participant population as control and experimental subjects (as with pre-post studies), or as multiple arms where different groups are compared with each other.7 Crossover study: A crossover study is a type of interventional study where the study participants serve as both control and experimental group at different times during the study. Subjects are initially treated as experimental or control group in phase one, followed by a washout period where the treatment is stopped, and then in phase two the groups are swapped into the other condition. This crossover design demonstrates reversibility of a treatment and compensates for unsuccessful randomization, as subjects now become their own controls.7
Observational Research Observational research studies examine the study and control groups to determine if they have different outcomes or risk factors that may be causal in determining those outcomes. Observational research can be prospective or retrospective depending upon the order of events within the project. When the project is designed first, and data collection follows, this is termed prospective. When the data have already been collected, as is the case of an EHR or registry, followed by development of a research question and study design, then the study is retrospective. Cohort study: Cohort studies are used to determine the incidence rate and natural history of a disease. A study population or cohort with a unique set of characteristics is defined and then followed the over time to determine if a certain outcome develops. Multiple outcomes and exposure variables can be studied in the same population. Prospective cohort studies are often inefficient, as it may take a long time for the outcome to occur, and during that time participant dropout often occurs. However, cohort study data can be examined retrospectively to answer new questions. Case-control study: The purpose of a case-controlled study is to determine the relative importance of specific factors in impacting an outcome.9 These studies are typically conducted retrospectively, and participants are identified based upon the outcome of interest, and then matched with a control group who does not have the outcome.8 This is a good study design if you are studying outcomes that are rare, but suffers from
sampling bias in that you cannot control the selection of participants in your dataset. This type of study works well for secondary data analysis, such as that obtained from the EMR, and can be used to determine the relative odds of a certain surgical outcome such as mortality, 30day readmission, or bleeding complication following a particular surgical intervention. Cross-sectional study: Cross-sectional studies are used to determine prevalence of a specific outcome and exposure status simultaneously in a population.8,9 Determining the prevalence of an outcome allows the physician to determine the likelihood of a particular diagnosis for a particular patient. These studies can be done prospectively or retrospectively, and their accuracy depends upon careful study group selection to avoid biasing the results. For an OEC, a cross-sectional study would be a good starting point to identify the baseline prevalence of certain conditions within your patient population that could be used as a basis for further intervention and research. This type of study is also useful for measuring the impact of quality improvement studies pre- and postintervention. Case report or case series: A case report or series is a description of a disease process in a single individual or several subjects without a control group. The cases described are typically a variation from what is commonly seen in a disease, including unique presentation of disease, novel patient populations, or adverse consequences of treatment. Case reports are often the first report to identify a new disease or adverse health effect. These types of reports are fast, easy, and inexpensive. Describing several cases simultaneously with similar features increases the evidence available to support a hypothesis, but without a control group you cannot provide conclusive evidence to support or refute a hypothesis.
Quality Improvement Quality improvement is a type of research that is focused on improving the processes within an organization to improve the quality, cost, and value of the care provided. The work is often focused on targeting a triple aim, with the goals of improving (1) the health of a community, (2) reducing the cost of medical care, and (3) improving the population’s experience within the healthcare system.10 With these goals in mind, there are many projects within an OEC that could be targeted, such as reducing cost of procedures for patients and the practice, improving the health outcomes of the community based upon preventative care, and improving the patient care experience while being treated at the OEC. Successful QI projects have a champion directing
CHAPTER 38
Conducting Research in an Office Endovascular Center
the project, who is invested in the outcomes. Thus, allowing operators or staff to identify areas they want to improve increases the success of QI projects. These concepts and methodology used in quality improvement are expanded further in Chapter 13.
Clinical Trials Clinical trials provide the evidence needed by the Food and Drug Administration (FDA) to evaluate the benefits and risks of a new medication or medical treatment to determine if it is safe for patients. In order to obtain the necessary data, thousands of patients are enrolled in clinical trials, many more patients than can reasonably be identified from a single institution. Participation in a clinical trial has several benefits: (1) the patients in your practice may benefit from novel drugs, devices, and treatments currently being studied; (2) the medical protocols within your OEC may change based upon new clinical evidence identified in the clinical trial and; (3) participating in a clinical trial is a good way to develop research experience and skills.11 Clinicians who have participated in clinical trials have also indicated that their clinic processes improved based upon documentation efforts required for the clinical trial, and that the profile of their practice has increased.11 A list of clinical trials currently being conducted can be found on the NIH website https://clinicaltrials.gov.
321
The Healthcare Cost and Utilization Project (HCUP): A repository of longitudinal statewide inpatient data. HCUP is the largest collection of hospital care data in the United States that includes all payers, encounterlevel data from 1988 to present.13 HCUP consists of several different databases including the National Inpatient Sample (NIS), the State Inpatient Database (SID), and the State Ambulatory Surgery and Services Databases (SASD). American College of Surgeons National Surgical Quality Improvement Program (ASC-NSQIP): A nationally validated, risk-adjusted, outcomes-based dataset that contains more than 28,000 cases with as many as 134 data points per patient tracked for 30 days after their operation. Currently, more than 710 individual hospitals have enrolled in this registry.14 Society of Vascular Surgery, Vascular Quality Initiative (VQI), and Patient Safety Organization (SVS-PSO): An aggregation and analysis of clinical data for patients undergoing specific vascular treatments designed to improve the quality, safety, effectiveness, and cost of vascular healthcare. Reports are generated twice per year to show trends, volume, process characteristics, and inhospital outcomes. The VQI consists of 12 registries with outcomes from more than 500,000 vascular procedures performed across the United States and Canada.15 Centers that participate in the VQI can compare their performance with region and national benchmarks.
Postmarket Studies Postmarket studies are studies conducted after the FDA has approved a product for marketing. They are typically sponsored studies that serve to collect additional information about a product’s safety, efficacy, and optimal use.12 These may include RCTs, drug interaction studies, efficacy studies, pharmacokinetic and pharmacodynamic studies, or pediatric trials. Some device companies pay for data to be collected if the OEC is a participant in a national registry.
RESEARCH RESOURCES Databases and Registries Beyond conducting research using the medical records or patients within your own practice, a number of resources exist that can be utilized for research including databases and patient registries (see also Chapter 19). Clinical registries have increasingly been generated from existing practice data for use as patient safety improvement tools, but can also be used as an observational database to address clinical research questions.
Medical Societies Numerous medical societies exist that may serve to foster research in the field. They provide an environment for researchers to identify mentors and collaborators, discuss the latest advancements in clinical research, promote discussions that stimulate research questions, or may provide registries or grants to further research. Relevant societies include the Society for Vascular Surgery, the Society for Vascular Medicine, the Society for Vascular Ultrasound, the Vascular and Endovascular Surgery Society, the International Society of Endovascular Specialists, American College of Cardiologists, Society of Interventional Radiology, and the Outpatient Endovascular and Interventional Society.
Practice-Based Research Networks Practice-based research networks (PBRN) are collaborations between clinical practice and academia designed to foster research.16 PBRNs connect healthcare to research by providing support to clinicians throughout the research process. These networks serve to help clinicians develop specific impactful research questions,
322
SECTION VII
Other Important Considerations
design and conduct studies, analyze data, and translate knowledge into practice. The PBRN network serves to better care for patients by conducting research in a patient population more representative of the general public, including patients with multiple comorbidities who are often excluded from RCTs. Additionally some diseases are only treated in certain settings making these topics more likely to be under represented in research studies.
Grants and Contracts For more extensive research projects, the project may require funding support to pay for personnel, resources, or services. The National Institute of Health is the leading funding resource for medical research in the United States, supporting more than 44,000 research projects in 2017.17 Starting in 2012, the National Center for Advancing Translational Sciences (NCATS) was established to fund translational research projects. Funding support for PBRNs can come from the Agency for Health Care Research and Quality (AHRQ). Funding may also come from local initiatives or societies as mentioned above. Many academic hospitals have award mechanisms that support the development of translational research or clinical trials. There are also nonprofit foundations, like the Kellogg Foundation, that support clinical research.
Regulations To ensure patient consent and understanding of the research, an informed consent document is an important part of any research project. For research studies that involve human subjects there are a number of ethical considerations that need to be accounted for before the research is initiated, including review of the research protocol by an institutional review board (IRB). If the OEC does not have access to the local IRB at an academic institution, there are regional IRBs that can be utilized to get project approval. Data obtained from medical records can be analyzed without informed consent as long as the findings of the project will not be published. For researchers interested in conducting quality improvement studies, this eases the burden of this hurdle, as long as they only report on the process utilized for improvement instead of the patient outcomes from the pre-post measures of their research.18 Institutional Review Board (IRB): The IRB is an ethical research committee, responsible for protecting the rights, welfare, and well-being of human research subjects.19 Most academic institutions have an IRB, which is responsible for reviewing research protocols to ensure
that the human subjects who will be asked to participate in that research are properly protected. Several factors are taken into consideration including the autonomy of the subject (their ability to opt in or out of the study), equitable selection of subjects, and the risk-benefits ratio of the study. Autonomy and consent are two of the cornerstone values in research ethics. The Declaration of Helsinki states that research “participants should be treated as autonomous beings capable of making an informed decision whether to participate in research.”20 In the case of database/EHR analysis at an OEC, individual patient consent can be obtained in their initial onboarding paperwork, or may be waived during the IRB review process if the research is determined to be of minimal risk to patients. The riskbenefit analysis helps the IRB determine how much risk the subjects will be exposed to in order to participate in the research, and what benefits will result from the study. The IRB reviews the research protocol including the scientific background of the project, rationale, objectives of the study, the study design, subject population (inclusion and exclusion criteria), subject recruitment, statistical analysis, expected results, study timeline, benefit and risk evaluation, dissemination plans, and any patient consent forms, surveys, or data collection forms that will be used in the study. Ethical considerations: Of recent concern is the involvement of physicians in clinical trials, as they and their patients may both benefit financially from enrolling in the research. Patients can benefit from enrolling in clinical trials through limited financial compensation and receipt of free healthcare. Financial incentives are one of the most important factors motivating physician involvement in research.21 Physicians are tasked with putting the concerns of their patient first above their own benefit, thus any incentives they receive must not influence their regard for their patients best interest.22 The IRB protocol should include measures that will be taken to avoid bias or influence of any financial incentives to study participation.
DATA COLLECTION Study Population The degree that the study population accurately represents the overall population of patients suffering from a disease or variable of interest determines the value and generalizability of the results. In the ideal situation, the characteristics of the study sample will directly match the overall population. Random sampling is the simplest method to match populations; however, depending upon the source of your study participants
CHAPTER 38
Conducting Research in an Office Endovascular Center
the study may already be biased, thus you may need to carefully design your study sampling method to account for these biases as much as possible. Careful consideration of all the variables that may impact your outcome, and devising methods to overcome these hurdles, will ensure selection of a study population that best represents the general population.
Sample Size The size of the study population should be predicted before the study begins. A statistician can use preexisting data about the outcome to help predict how many subjects need to be enrolled to adequately power the statistical analysis. Enrolling more subjects than is needed is costly and adds difficulty to the research project, but enrolling too few may mean the study fails to detect relationships that exist between variables and outcomes, and inadequately addresses the research question.23 A statistical power analysis will determine the probability that the study can identify relationships that exist in the data.
Data Collection Tools Care should be taken during the data collection phase to ensure that the data are accurate, complete, and organized. Missing values or duplication of records can cause problems down the road. A number of tools exist that can support the data collection process. For studies utilizing data in an EHR, the data can be obtained from an information technologist who can export a certain dataset with the variables of interest. However, not all EHRs are designed for research, thus the data may need to be abstracted from the medical record by study team members. Above all, the researchers must ensure that the subjects in their study are protected, this means developing a data management plan to protect any PII. Data may be collected into a simple password-protected database or into a tool designed for research data collection such as REDCap (Research Electronic Data Capture).24 REDCap is a HIPAA-compliant data collection tool that enables academic researchers to develop surveys or data collection instruments.
DATA ANALYSIS Analysis of the data is the most exciting aspect of the study, as you can finally begin to answer your question. With most medical questions the answer is rarely black or white, instead we are asking about the probability that a variable impacts an outcome. Statistics allows us to measure these probabilities. To get an accurate answer to the research question, an expert, typically a
323
statistician, should conduct the analysis. Utilizing the appropriate data analysis method depends on the study design, variables collected, and desired outcome. Data analysis tools should be identified in the design phase of the study.
PRESENTING YOUR FINDINGS
Research findings should be disseminated beyond your group to maximize the benefits of conducting a project. Publication is the ultimate goal, creating a permanent record of the research and its findings. The work can also be disseminated at local, regional, or national conferences by submitting an abstract for presentation in a poster or oral format. While clinical research studies have clear value, quality improvement studies describing the process of improvement utilized to achieve your goals can also be published and are valuable to other groups who are attempting similar initiatives for improvement. To ease the burden of the presentation process, collaboration with an academic colleague or with a medical writer or editor can help by providing knowledge of the publication process.
PARTNERING WITH A MEDICAL SCHOOL For many of the topics discussed above, access to resources and individuals who can collaborate on your project can be facilitated through partnering with a medical school. You can gain access to a number or resources including the library, students and residents, grants management, statisticians, medical editors, management of industry contracts, and colleagues. Due to the complexity and regulations surrounding a clinical trial, medical schools often have entire departments dedicated to ensuring compliance with FDA regulations.25 Partnering with the medical school may be done through collaborations with medical school faculty or by joining a medical school as community faculty. At most medical schools, community faculty are volunteers who contribute to education, research, community engagement, and committees at the medical school. In return, community faculty gain access to the medical school resources described above in addition to opportunities for continuing education. For many medical schools their required commitment is minimal, often 25e50 h of service per year. For OECs looking to collaborate on research projects, committing to include students and residents on your research projects may satisfy these requirements.
324
SECTION VII
Other Important Considerations
FINAL CONSIDERATIONS Conducting research requires an investment of time, resources, and effort toward a project. As research projects always take more time than anticipated, the research team must be fully invested and interested in the project to dedicate the time needed to move the project forward and successfully accomplish their goals. Numerous students and residents are interested in participating in research, but they often fail to realize the time commitment required. Setting clear expectations of time, investment, and quality is important to make sure the mentor-mentee relationship is built on common ground. Thus careful selection of students or residents is critical to both advance the project and generate a good mentor-mentee relationship that will be mutually beneficial. Similar care should be taken in identifying collaborators that have the needed skills for a project.
CONCLUSION Research is essential to address questions that arise during the practice of medicine. While some questions can easily be addressed with a literature search, true research problems will have unanswerable questions that require research to solve. An OEC has a responsibility to provide the best patient care possible and to do this; research is a necessary aspect of patient care. Through contributing to registries, undertaking quality improvement studies, or answering unanswered questions, physicians of an OEC can make meaningful contributions to improving medical care provided. Not only does this research directly benefit the OEC, but it also can benefit the field of endovascular medicine.
REFERENCES 1. Cripe TP, Thomson B, Boat TF, Williams DA. Promoting translational research in academic health centers: navigating the “roadmap,”. Acad Med. 2005. https://doi.org/ 10.1097/00001888-200511000-00008. 2. Alon U. How to choose a good scientific problem. Mol Cell. 2009;35:726e728. https://doi.org/10.1016/j.molcel.2009. 09.013. 3. Evidence-Based Medicine Resource Guide. Georg. Univ. Dahlgren Meml. Libr.; 2019. 4. Morrison-Beedy D, Aronowitz T, Dyne J, Mkandawire L. Mentoring students and junior faculty in faculty research: a win-win scenario. J Prof Nurs. 2001. https://doi.org/ 10.1053/jpnu.2001.28184. 5. Mabvuure NT. Twelve tips for introducing students to research and publishing: a medical student’s perspective. Med Teach. 2012;34:705e709. https://doi.org/10.3109/ 0142159X.2012.684915.
6. Richardson WS, et al. The well built clinical question: a key to evidence based decisions. ACP J Club. 1995. https:// doi.org/10.7326/ACPJC-1995-123-3-A12. 7. Thiese MS. Observational and interventional study design types; an overview. Biochem Medica. 2014. https://doi.org/ 10.11613/BM.2014.022. 8. Noordzij M, Dekker FW, Zoccali C, Jager KJ. Study designs in clinical research. Nephron Clin Pract. 2009. https:// doi.org/10.1159/000235610. 9. Mann C. Observational research methods. Research design II. Emerg Med J. 2003. https://doi.org/10.1136/emj.20.1.54. 10. Triple Aim for Populations. Inst. Healthc. Improv.; 2019. http://www.ihi.org/Topics/TripleAim/Pages/Overview.aspx. 11. Batchelor JM, Chapman A, Craig FE, et al. Generating new evidence, improving clinical practice and developing research capacity: the benefits of recruiting to the U.K. Dermatology Clinical Trials Network’s STOP GAP and BLISTER trials. Br J Dermatol. 2017. https://doi.org/ 10.1111/bjd.15959. 12. Postmarketing clinical trials, U.S. Food drug Adm. 2018. 13. HCUP Overview. Healthcare Cost and Utilization Project (HCUP). Agency Healthc. Res. Qual.; 2018. https://www. hcup-us.ahrq.gov/overview.jsp. 14. Ingraham AM, Richards KE, Hall BL, Ko CY. Quality improvement in surgery: the American College of Surgeons national surgical quality improvement program approach. Adv Surg. 2010. https://doi.org/10.1016/j.yasu.2010.05.003. 15. Vascular Quality Initiative, (2019). https://www.vqi.org/. Accessed October 18, 2019. 16. Pirotta M, Temple-Smith M. Practice-based research networks. Aust Fam Physician. 2017;46(10):793e795. 17. RePORT. Funding Facts. Natl. Institutes Heal.; 2018. https://report.nih.gov/fundingfacts/fundingfacts.aspx. 18. Feldman SR. Participating in trials can inform better clinical practice. Br J Dermatol. 2017;177:1148e1149. https://doi.org/10.1111/bjd.15946. 19. Institutional Review Board Guidebook. Off. Hum. Res. Prot.; 2019. 20. World Medical Association. Declaration of Helsinki world medical association declaration of Helsinki. Bull World Heal Organ. 2001. doi:S0042-96862001000400016 [pii]. 21. Rahman S, Majumder A, Shaban S, Rahman N, Ahmed SM, Abdulrahman K, Dsouza UJ. Physician participation in clinical research and trials: issues and approaches. Adv Med Educ Pract. 2011. https://doi.org/10.2147/amep.s14103. 22. Fisher JA. Practicing research ethics: private-sector physicians & pharmaceutical clinical trials. Soc Sci Med. 2008. https://doi.org/10.1016/j.socscimed.2008.02.001. 23. Suresh G, Suresh K, Thomas S. Design, data analysis and sampling techniques for clinical research. Ann Indian Acad Neurol. 2011;14:287. https://doi.org/10.4103/09722327.91951. 24. REDCap: Research Electronic Data Capture, (n.d.). https:// projectredcap.org/about/(accessed March 29, 2019). 25. Arbit HM, Paller MS. A program to provide regulatory support for investigator-initiated clinical research. Acad Med. 2006. https://doi.org/10.1097/00001888200602000-00009.