2 The Value of Clinical Research
Michael B. Wallace and Peter D. Siersema
In this review, we will cover major topics relevant to the performance and communication of clinical research, including key issues such as the value to clinical care, keys to conducting research, and how to build teams of successful researchers within institutions and between institutions. We will provide a basic overview on how to design clinical trials, generate research ideas, write grants, and conduct day-to-day clinical research. We will provide valuable information on how to present at national and international meetings and write and publish manuscripts. Finally, we will cover issues such as ethics and the future of scientific publications.
Clinical research provides value through guiding physicians and other caregivers on how to choose the optimal method of diagnosing and treating diseases. It is fundamentally different from basic research, which focuses on mechanisms of diseases as well as normal and abnormal biological processes. Clinical research particularly focuses on the patient. In our daily practice, we struggle through decisions in virtually all patients including, which diagnostic tests to perform, what the optimal treatments are, and how to deal with the costs and adverse effects of our diagnostic and treatment approaches. It is widely acknowledged that there are major gaps in our knowledge. High-value clinical research should include several key elements including:
Selecting clinically relevant interventions for comparison to current standards of care.
Inclusion of relevant and diverse populations.
Collection of health-related outcomes important to patients, physicians, and payers.
All clinical trials should be performed in a rigorous scientific manner that adheres to several key principles to provide accurate and reliable information. 1 Studies performed in a highly selected group of patients, who are fundamentally different from the patient we are currently caring for, do not provide reliable guidance. The value of clinical trials is only as great as the extent to which those results are communicated and made available to patients, colleagues, and providers. The process of scientific publication has long been the mechanism by which we communicate these results, although many other options are increasingly available; such as communication at scientific conferences, internet, and social-media based methods of data sharing.
2.2 Keys to Success
Clinical research is both tremendously rewarding and challenging. Over many years of conducting research we have defined four key elements to success:
A tough skin.
A team approach.
Attention to detail and a questioning approach.
Having long-term as well as short-term goals.
2.2.1 A Tough Skin
Even the most successful clinical investigators face many hurdles while conducting and publishing clinical research. Most competitive medical journals have acceptance rates of well under 20%. Large federal grants are even more competitive with funding rates now less than 10%. Thus, even excellent research proposals and papers may be rejected for funding and publication. To ultimately succeed, clinical investigators must be willing to accept the short-term failures and persist in conducting and publishing the research they believe in.
2.2.2 Building Teams
Building teams enables each member of the team to bring unique talents and ideas to a research project. Many of the best research projects occur at the boundary zones between different areas of expertise. A specific example of this is our research on the role of endoscopic ultrasound in lung cancer. 2 , 3 Both the field of endoscopic ultrasound and the field of lung cancer were represented by very different groups of physicians; however, working together identified unique contributions of each team. Beyond physicians, a successful team should include senior mentors, junior investigators, statisticians, experts in clinical trial design, study coordinators, and editorial assistants.
Fellows play one of the most important roles in the team. For the fellow, the goals are to perform the research and to learn the process. The only way to do this, is to practice. Most academic medical centers include research activities as a part of their core curriculum. In addition to clinical fellows, who spend part of their time doing research, many programs offer dedicated research fellowships in clinical investigation. These programs often include dedicated training in research methodologies and advanced degrees such as a Master or Doctoral degree. Such didactic training has been shown to increase the likelihood of long-term research success. 4
Research collaboration, both within an area of interest and across disciplines, fosters long-term academic productivity. In addition, collaboration with colleague researchers in other centers, both on a national and international level, often increases the clinical value of observations. Developing a long-term plan to integrate with other colleagues is critical. Key elements of this include shared authorship and shared responsibilities, both of which are best outlined at the beginning of a study. A challenging issue for many large groups is authorship on manuscripts. Overall, it is best to acknowledge the contributions of each member either throughout authorship, if they meet guidelines, or through acknowledgment. It is important to recognize that it is not necessary to include a division chair on every manuscript. The International Committee of Medical Journal Editors (ICMJE) provides widely accepted definitions of authorship. 5
Study coordinators do the majority of the day-to-day work of clinical trials. Clinical coordinator should be chosen based on the skills necessary for each trial. In some cases, a nurse is required when important clinical decisions need to be made. In other circumstances, data coordinators can collect clinical trial information in a reliable and efficient manner. Coordinators should be respected members of the team who are included in research planning discussions and acknowledged in manuscripts.
Statisticians play a key role in the design and analysis of studies. A common mistake is to involve statisticians only at the end of the study when analysis is needed. A much more effective strategy is to involve statisticians at the planning stages. In this way, variables can be carefully defined and chosen in a way that will optimize data analysis. Statisticians can also significantly improve the overall study design. For example, simple changes in study design can substantially alter the sample size needed. 6
Finally, partnering with editorial assistants may be highly valuable for some investigators. The skill of writing manuscripts is very different than the skill of conducting research. Many large academic centers have medical editors who can facilitate how we communicate our scientific discovery with the broader community.
2.3 Designing Clinical Trials
The field of endoscopy has matured substantially over the past 20 to 30 years. From one where simply describing our observations and experience was enough to be published, to now where competitive journals typically only publish well-designed controlled clinical trials and cohort studies. In order to be published, such high-quality clinical studies should be carefully designed to achieve our primary goal of seeking scientific truth. Designing clinical trials follows a general pattern from generating ideas, to study design, to grant writing, and finally completion of the study. Each of these is discussed further.
2.3.1 Generating Ideas
Generating ideas should be the easiest of all research activities. All those involved in patient care know that many decisions we make, for both diagnosis and treatment, have only a limited amount of scientific evidence. Thus, in almost every patient encounter, we can identify opportunities for research.
2.3.2 Refining Ideas
Many studies can take months or even years to complete, so the long list of possible research topics needs to be refined based on several key factors:
Is the topic of high interest to the investigator?
Are the resources to study the question available to the investigator, including adequate numbers of patients, access to large databases, collaborators with sufficient expertise, and funding sources?
Research questions should be further defined based on a very detailed review of the current literature. Ultimately, research is aimed at extending the envelope of knowledge beyond what is currently known. Many resources are available (PubMed, Google Scholar, Medline, etc.) to identify current knowledge and its gaps including review of published research and consultation with other experts. Almost all published studies end with a statement such as “further research is necessary to confirm/clarify….” These statements offer excellent clues on how to further refine a specific research question. Moreover, some outcomes need to be confirmed or even excluded because they seem clinically not rational.