This topic will review activities that are typically undertaken at an investigational site while conducting a study.
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Hi, I’m Dr. Lisa Epps. I have been working as a Clinical Investigator for 10 years. One of my favorite tasks is to introduce professionals to the discipline of clinical research. Today I am sharing what it takes to conduct a study with Miguel Lopez, who just started working as a Clinical Study Coordinator.
To conduct a study successfully, it is necessary to be able to identify and distinguish the stages of a study, and understand the tasks and activities associated with each stage. A successfully conducted study will provide high quality, reliable, data and ensure that the rights, safety, and welfare of the subjects are being protected.
This topic will provide more information on:
· The stages of a clinical study after study start-up, that is,
§ Subject Enrollment,
§ Ongoing Conduct, and
§ Subject Exit or study completion
· The tasks and activities associated with these stages
An Investigator preparing to conduct a study will begin with study start-up, which starts with the Feasibility process. During feasibility, the Sponsor and the Investigator determine if the Investigator has the knowledge, resources, subjects, and interest to conduct the study. Once this is confirmed, the Investigator participates in the Qualification process during which the feasibility information is explored in more depth to determine if the Investigator should be selected for participation. If selected, the Investigator is then initiated, which means that required training, approvals, and resources are put in place to conduct the study. The investigator cannot begin participation in the study until these activities are completed. After the investigator is initiated in the study, the next stage, the Study Conduct stage, begins. We will concentrate on this stage for the remainder of this topic.
Once all subjects have completed or exited the study, the Study moves from the Study Conduct stage to the study Close-out stage, in which study related activities at the site are completed in an organized manner.
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Predicting and meeting your enrollment commitments for a study requires careful thought and preparation including planning around how you will Identify, Recruit and Qualify potential subjects. Let’s look at these areas in more detail over the next few pages of this topic.
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Once you have a clear picture of what the appropriate subject for the study looks like, you will begin planning for recruitment. Often, when they actually start enrolling subjects for a study, Investigators are surprised to find that it is more difficult than they had expected. Most Sponsors will require that you provide initial information during the study feasibility or the Site Qualification Visit, that is, before the Sponsor decides on site selection. As an Investigator working on subject recruitment, try to answer the following question: How many subjects do I see with this indication? The number that comes up will comprise of your subject population.
Within this subject population, how many are likely to meet the inclusion and exclusion criteria for the study? This is your potentially qualified subject pool. Of potentially qualified subjects, how many are realistically likely to be interested in participating in a clinical study? If your site does not regularly participate in research, this may be a new concept for your subjects. Of your subjects who may be interested, how many consent after you explain the study and are able to be compliant? And of those, how many satisfy all entry criteria and enroll?
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Miguel Lopez:
Dr. Epps, are there any challenges in the recruiting process?
Dr. Epps:
Well, as you can see, the potential subject pool becomes smaller and smaller with each step. It is therefore important to be realistic when determining if your practice will be able to provide enough subjects to meet subject enrollment expectation. And even with all the estimates in place, your recruitment plan should still have a back-up strategy, in case the initial approach is found to be not effective. For example, if you fail to provide enough potential subjects, or cannot recruit the potential number within the enrollment period, what resources can you utilize to help meet the subject enrollment expectations? To prepare for this, you can collaborate with the Sponsor and also ask other sites about their successful recruitment strategies. Some examples of recruitment strategies are: reviewing patient charts and hospital records, patient referral groups, TV and Newspaper advertisements, or notices in the waiting room. It might depend on your local regulations if you can use all, or only some of these recruitment strategies.
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The screening of subjects is the first step to determine if they qualify for study participation.
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Enrolling a subject who does not qualify for the study can put the subject’s safety at risk, as well as compromise the integrity of the study data. Following some simple steps will ensure that you have selected qualified subjects.
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Good job! You’ve just completed reviewing the enrollment stage of conducting a clinical study. Now, let’s take a look at the Ongoing Conduct stage. In this stage, you will have active subjects in the study. Key components of study conduct include knowing the schedule of events for subjects, reporting data, handling deviations, and retaining subjects in the study. Let’s look at these areas in more detail.
Missing study data and errors in processes undermine the analysis both for the subject and for the entire study. Planning for all visits and procedures required, and for the sufficient supply of Investigational Product, is therefore critical to the success of the study.
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The data you collect is critical to the study. Let’s take a look at how you report data to the Sponsor. Note that we will not discuss reporting Safety Events here, as there is a separate informational topic covering Adverse Events & Safety.
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Recently, I sat down with Dr. Epps to understand the significance of deviations from the Study Protocol. It was very helpful! Did you know that deviating from the approved Study Protocol can place a subject at risk as well as compromise the study results? Let’s review Dr. Epp’s explanations further.
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Miguel Lopez: Dr. Epps, first of all: What are the expectations regarding the compliance with the Study Protocol?
Dr. Epps: According to ICH-GCP section 4.5, the Investigator or institution should conduct the study in compliance with the Study Protocol agreed to by the Sponsor, and, if required, by the Regulatory Authority(ies), and which was given approval or favorable opinion by the IRB/IEC.
The Investigator should not implement any deviations or changes from the Study Protocol without agreement by the Sponsor and approval by the IRB/IEC, except where necessary to eliminate an immediate hazard to the subject.
Miguel Lopez: What should we do in case a deviation has occurred, despite our best efforts to adhere to the Study Protocol?
Dr. Epps: It is important that deviations be documented and reported to the Sponsor/Sponsor representative. Deviations often require reporting to your IRB/IEC as well- please familiarize with the IRB/IECs specific reporting requirements. In some deviation cases, the subject may no longer be eligible to continue in the Study Protocol. It is important to communicate any deviations to the Sponsor.
Reporting is only part of effective management of deviations. The root cause of the deviation must be determined and documented and based upon that, effective actions must be taken to address the current deviation. This is known as the corrective action plan. You should also plan actions to prevent the deviation from reoccurring. This is known as the preventative action plan. The whole process must be documented.
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Good job! You’ve just completed reviewing details of the Ongoing Conduct stage of a clinical study. Now, let’s take a look at the subject exit or completion stage. This is the stage where your patients are exiting the study. Some patients may exit the study prematurely. Others will finish the study as per protocol. Let’s look at some important points to consider for this stage.
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In summary, being able to describe and distinguish the different stages of a clinical study, and the tasks and activities associated with them, are instrumental for the successful conduct of the study. A successfully conducted study will ensure the collection of high quality, reliable, data, and ensure that the rights, safety, and welfare of the subjects are being protected.
The three stages of Study Conduct are subject enrolment, ongoing conduct, and subject exit or completion. Key activities in study conduct include the selection of eligible subjects, planning the visit flow, and management of any protocol deviations.
· Understanding the stages of a clinical study will help ensure that we:
§ Collect high quality, reliable data
§ Protect the rights, safety, and welfare of subjects
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Attributable, legible, contemporaneous, original, accurate
A procedure in which one or more parties in the trial are kept unaware of the treatment assignment(s). Single blinding usually refers to the subject(s) being unaware, and double blinding usually refers to the subject(s), investigator(s), monitor, and, in some cases, data analyst(s) being unaware of the treatment assignment(s).
Complete, consistent, enduring, available
A paper or electronic copy of the original record that has been verified (e.g. by a dated signature) or has been generated through a validated process to produce an exact copy having all of the same attributes and information as the original.
Code of Federal Regulations
Collaborative Institutional Training Initiative
Federal Commission for the Protection against Sanitary Risk (Mexico)
Action to eliminate a detected nonconformity
Clinical Research Coordinator
Case Report Form
Contract Research Organization
Clinical trial agreement or study contract
Curriculum vitae
Electronic Data Capture
European Medicines Agency (Europe)
Electronic Medical Record
Food and Drug Administration (USA)
Good Clinical Practice; A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected
Investigator Brochure
Informed Consent Form
The short form of ‘International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use’. ICH is unique in bringing together the regulatory authorities and pharmaceutical industry of Europe, Japan and the US to discuss scientific and technical aspects of drug registration.
Independent Ethics Committee
A person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial, who attends the informed consent process if the subject of the subject’s legally acceptable representative cannot read, and who reads the informed consent form and any other written information supplied to the subject
Investigational New Drug
Any public or private entity of agency or medical or dental facility where clinical trials are conducted
A person responsible for the conduct of the clinical trial at a trial site.
Investigational Product
Institutional Review Board
Investigator Study File
Interactive Response Technology, also referred to as IRT or IWRS depending on the type of technology used
Medicines and Healthcare Products Regulatory Agency (United Kingdom)
New Drug Application
National Institute for the Control of Pharmaceutical and Biological Products (China)
Notice of Initiation of Disqualification Proceedings and Opportunity to Explain
National Institute of Health
Non Investigational Product
Notice of Opportunity for Hearing
Action to eliminate the cause of a potential non-conformity or other undesirable situation
The process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce bias
A method of problem solving used for identifying the underlying causal factor of the noncompliance. If the root cause is removed the error is prevented from recurring.
Serious Adverse Event
Standard Operating Procedure; detailed written instructions to achieve uniformity of the performance of a specific function
An individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial
The term unmasked is equivalent to the term unblinded. Unblinded/ unmasked can refer to a role in the study execution in which one party involved in the trial does know the treatment assignment. This strategy may be used for studies where a matching comparator is not available.