1. Fowler, Susan B.
  2. Stack, Katherine

Article Content

Research is systematic inquiry that uses orderly scientific methods to answer questions or solve problems (Polit & Beck, 2004). Clinical nursing research is a term applied to scientific study that focuses on the clinical setting. The common thread throughout clinically focused research is the human response to actual or potential health problems. Research priorities range from very specific topics like determining whether end-tidal CO2 monitors are reliable in infants with very low birth weights (American Academy of Pediatrics, 2005) to more general topics like creating a healing, humane environment (American Association of Critical-Care Nurses, 1999).


Research with a focus on clinical trials is a very specific type of research. A clinical trial is defined as a research study that involves human participants and is designed to answer specific health questions about how to control or cure disease and how to enhance health (Habel, 2005). Key elements of clinical trials are a prospective approach, study of a specific intervention, and comparison to a control group that does not receive the intervention.


Four phases of clinical trials have been defined by government agencies (National Institutes of Health [NIH], 2005). Phase I trials are studies being performed for the first time in humans; they involve healthy volunteers (<100) and explore the safety and toxicity of an intervention. Investigators seek to determine how well an intervention is tolerated. Sufficient information about a drug's pharmacokinetics and pharmacological effects need to be obtained from this initial investigation in order to proceed to the design of a well-controlled, scientifically valid Phase II study. For example, a present Phase I clinical trial focuses on a rationally engineered drug with better stability, toxicity, and efficacy than other current FDA-approved drugs for refractory or metastatic solid tumors.


Approximately 100-300 individuals with a specific disease are involved in Phase II clinical trials, which investigate safety, efficacy, and dose adjustments. The effect of an intervention is sought, as well as an understanding of adverse events (AEs) associated with the intervention. An example of a Phase II study would be administering varying doses of a chemotherapy agent intraoperatively in malignant brain tumor patients.


As part of a consideration of indications for labeling and continued safety and efficacy, thousands of participants are enrolled in multisite, randomized, blinded, placebo-controlled Phase III studies. New treatments are compared with the best currently available or standard treatment. An adequate basis of information must be generated from Phase III studies to extrapolate results to the general population and transmit information for labeling. A Phase III trial listed on targets an ointment with nitroglycerin to relieve Raynaud's symptoms and increase blood flow to fingers.


Finally, a study completed after marketing has been approved is a Phase IV trial, which examines new indications, dosing strategies, new patient populations, and quality of life. These studies involve drugs that are already available for licensed practitioners to prescribe to patients. Studying a medication approved for seizures for a specific type of pain would be an example of a Phase IV trial.


In clinical trials, the actual title given to a nurse varies and may include research nurse, research coordinator, clinical research coordinator, research clinician, or clinical trials coordinator. Regardless of the title, nurses engaged in clinical trials develop, coordinate, and implement research and administrative strategies essential to the successful management of research conducted by principal investigators (PIs). Nurses perform a variety of duties involved in the organization, oversight, documentation, and compilation of clinical research data. The education level required for a position as a clinical trials coordinator is not standard, but often a bachelor's degree with related clinical trials research or other closely related research experience is recommended.


Nurses can also serve as PIs or coinvestigators. As coinvestigators nurses


* determine participant eligibility


* obtain informed consent


* collaborate with other members of the study team


* assist with study drug administration


* monitor participants using specific assessment scales


* gather information on serious adverse events (SAE)


* participate in causality determination for SAEs.



Previous experience as a study coordinator can enhance the role of coinvestigator. A major responsibility of a study coordinator is creating the chart of a participant enrolled in a clinical trial. Demographic information, a signed medical release form, documentation of the informed consent process, the consent, a checklist of inclusion and exclusion criteria, a concomitant medication list, a medical history, a physical examination, visit-specific procedures, and a description of AEs are essential elements of the participant's chart. Managing participant records requires organization, attention to detail, and timely completion.


Nurses engaged in clinical trials, regardless of their role, must have a thorough understanding of the institutional review board (IRB) role and reporting requirements. Research proposals need to be reviewed to ensure protection of human rights. The core element is the informed consent. Nurses involved in research should consult the IRB prior to official submission of the proposal and informed consent form to learn of specific individual IRB requirements. It is often helpful for a nurse new to clinical trials to look at consent forms that have already been approved by an IRB.


IRBs often have a template for an informed consent form that incorporates essential elements including eligibility requirements, study purpose and description, duration of the study, risks and benefits, other options, compensation, and acknowledgment of an understanding of study participation and the consent form. The challenge for the clinical trials coordinator is to blend or combine the proposed informed consent provided by the study sponsor with the individual institution's suggested format and requirements.


Experience has taught all who are involved with clinical trials that risks of study participation, in particular, need to be explicit. If possible, the duration of risk should be identified. Institutions need to know whether any compensation is available if the participant experiences injury as a result of participation in the study and who will pay for related treatment. For example, it should be clear that the hospital will provide medical care but that it will not pay for injury-related treatment; instead, the participant's insurance will be billed accordingly.


Consent forms must contain all components required by regulations from the Food and Drug Administration (1998) and the International Conference on Harmonization (1996). A copy must be provided to the participant. Dated footers on the consent will help distinguish versions, because changes may occur before the start of the study as well as during the trial period. The clinical trials coordinator is the key individual for modification of consents, ensuring placement of consent forms in participants' medical records and study binders and communication with the IRB regarding requested changes to the informed consent.


Research participants need to be informed of multiple aspects of a clinical trial including


* why the study is being done


* who is conducting the study


* who is going to be in the study


* what kinds of tests and treatments are involved


* how long the study will last


* who will pay for the study (Habel, 2005).



The important issue is whether potential participants have a clear understanding of what participation in the study involves and what risks and benefits are entailed (Sosin, 2004). Although the ultimate responsibility for the participants' understanding of the study and consent lies with the PI, the study coordinator has a crucial role in making sure that participants have thorough understanding through frequent and thorough explanations and in providing adequate time for participants to comprehend the information (Hinkle & Bowman, 2002; Sosin).


Nurses engaged in clinical trials must have a thorough understanding of the institutional review board role and reporting requirements.


Full review of the study protocol, informed consent, and IRB application is required for most clinical trials because participant risk can be significant and participation involves more than simply completing questionnaires or other forms. The trials coordinator assists the PI with the IRB application process and submission of necessary documents. Attendance at the IRB meeting when the study is reviewed can help the coordinator better understand the research process and assist the PI in responding to questions related to the study.


All AEs occurring in a clinical study must be reported. An AE is a new event that the participant experiences following enrollment in the study. It is a deviation from the participant's baseline health. A thorough medical history and physical examination provide the foundation for determining an AE. Although this baseline information is often the responsibility of the PI, the coordinator collaboratively assists with gathering information. A worsening baseline condition is considered an AE. No causal relationship of the event to the study intervention (e.g., a drug) is implied with an AE. It can range from constipation to a broken leg.


An AE becomes an SAE when it results in death, a life-threatening situation, a significant or persistent disability, or an unplanned hospitalization or a prolonged existing hospitalization. The AE of a broken leg that requires hospitalization for surgical intervention is an SAE. All SAEs, regardless of their relationship to the study intervention, must be reported immediately to the sponsor. A nurse as a clinical trials coordinator has the necessary skills to gather all data related to an SAE and complete the required paperwork and reporting. Nurses have the knowledge and expertise to understand an SAE, gather relevant data, and assist study team members with interpretation of the situation. The coordinator assists the PI with determination of causality, although the ultimate determination is done by the PI.


The study coordinator works closely with personnel monitoring the study. Monitoring visits take preparation and time. Problem areas often are found with the informed consent, protocol conduct, deficient records, drug supply, IRB contact, and missing records. Problems with the consent often stem from inadequate control of the version in use, no evidence of the consent process in the medical records, and missing signatures on the form itself. The clinical trials coordinator must be organized and must develop a system of document collection to ensure few deficiencies in documentation.


IRB issues are related to tardy reporting of AEs, failure to report changes in the statement of the PI or the resignation of the subinvestigator, and failure to submit final reports to the IRB. Missing records might include expired or missing medical licenses and curricula vitae that are not updated, signed, and dated. Drug accountability must be maintained, with logs updated on an ongoing basis, corrections made in the right manner, and unused or empty containers retained. Attention to detail is critical to prevent such errors. Most identified problems can be correctly and collaboratively resolved by the study coordinator, monitor, and PI.


Research ethics have evolved over time (NIH, 2006). The Nuremberg Code, established after World War II, clarified many basic principles of ethical research conduct and focused on voluntary informed consent. The World Medical Association created the Declaration of Helsinki in 1964, which stresses that the well-being of the research participant should take precedence over the interests of science and society. The declaration also recommends written informed consent. The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research (U.S. Department of Health, Education, and Welfare, 1979) resulted from awareness of the Tuskegee study in which 400 men with latent syphilis were followed for the natural course of the disease rather than receiving treatment. Respect for persons, beneficence, and justice are the three fundamental principles for ethical conduct of research involving human research participants.


The Association of Clinical Research Professionals (ACRP, 2004) has a code of ethics that nurses involved in clinical trials should uphold and practice. ACRP recommends that research personnel


1. hold the safety and welfare of human participants as their highest goal


2. execute work according to scientific standards of objectivity, accuracy, and integrity


3. advance their knowledge and understanding through education and training


4. safeguard the quality and credibility of professional judgment from inappropriate influence


5. ensure that principles of informed consent are honored in spirit and in practice.



In addition, research personnel should maintain the confidentiality of all records and communications, make full disclosure in advance of engaging in research, and feel comfortable challenging the practices of others that may be detrimental to good clinical practice.


Nurses employed as clinical trial coordinators face challenges in study implementation. Coordinators must strive for understanding of the research protocol by PIs. Although most coordinators intimately understand the protocol, the ultimate responsibility lies with the PI. Working closely with multiple disciplines to adhere to protocol requirements that involve more than the standard of care requires communication, support, and appreciation of efforts (Rice & Cheak, 2000). For example, getting radiologists to read scans in a different way may take time and constant communication. The study coordinator should be readily available for consultation with staff nurses and others concerning the applicable details of a given study (Hinkle & Bowman, 2002).


Strategies to enhance the professional growth of a study coordinator include involvement in various types of trials or clinical areas and greater responsibility for regulatory requirements. A study coordinator who focuses primarily on pharmaceutical trials may want to become involved in clinical trials involving equipment and procedures.


Study coordinators receive many personal and professional rewards. For some, the ability to spend more time with patients and their families gives the most satisfaction. Many nurses who work in clinical trials comment on the autonomy afforded them, which capitalizes on nursing professionalism. Nurses also enjoy the collaborative relationships with other members of the research team and find that such collaboration fits well with nursing. The diversity of tasks and flexibility of involvement in acute and preventive studies are another attraction for study coordinators.




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