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Understanding Clinical Trials

Clinical research: what is it.

Your doctor may have said that you are eligible for a clinical trial, or you may have seen an ad for a clinical research study. What is clinical research, and is it right for you?

Clinical research is the comprehensive study of the safety and effectiveness of the most promising advances in patient care. Clinical research is different than laboratory research. It involves people who volunteer to help us better understand medicine and health. Lab research generally does not involve people — although it helps us learn which new ideas may help people.

Every drug, device, tool, diagnostic test, technique and technology used in medicine today was once tested in volunteers who took part in clinical research studies.

At Johns Hopkins Medicine, we believe that clinical research is key to improve care for people in our community and around the world. Once you understand more about clinical research, you may appreciate why it’s important to participate — for yourself and the community.

What Are the Types of Clinical Research?

There are two main kinds of clinical research:

Observational Studies

Observational studies are studies that aim to identify and analyze patterns in medical data or in biological samples, such as tissue or blood provided by study participants.

Clinical Trials

Clinical trials, which are also called interventional studies, test the safety and effectiveness of medical interventions — such as medications, procedures and tools — in living people.

Clinical research studies need people of every age, health status, race, gender, ethnicity and cultural background to participate. This will increase the chances that scientists and clinicians will develop treatments and procedures that are likely to be safe and work well in all people. Potential volunteers are carefully screened to ensure that they meet all of the requirements for any study before they begin. Most of the reasons people are not included in studies is because of concerns about safety.

Both healthy people and those with diagnosed medical conditions can take part in clinical research. Participation is always completely voluntary, and participants can leave a study at any time for any reason.

“The only way medical advancements can be made is if people volunteer to participate in clinical research. The research participant is just as necessary as the researcher in this partnership to advance health care.” Liz Martinez, Johns Hopkins Medicine Research Participant Advocate

Types of Research Studies

Within the two main kinds of clinical research, there are many types of studies. They vary based on the study goals, participants and other factors.

Biospecimen studies

Healthy volunteer studies.

Clinical trials study the safety and effectiveness of interventions and procedures on people’s health. Interventions may include medications, radiation, foods or behaviors, such as exercise. Usually, the treatments in clinical trials are studied in a laboratory and sometimes in animals before they are studied in humans. The goal of clinical trials is to find new and better ways of preventing, diagnosing and treating disease. They are used to test:

Drugs or medicines

New types of surgery

Medical devices

New ways of using current treatments

New ways of changing health behaviors

New ways to improve quality of life for sick patients

 Goals of Clinical Trials

Because every clinical trial is designed to answer one or more medical questions, different trials have different goals. Those goals include:

Treatment trials

Prevention trials, screening trials, phases of a clinical trial.

In general, a new drug needs to go through a series of four types of clinical trials. This helps researchers show that the medication is safe and effective. As a study moves through each phase, researchers learn more about a medication, including its risks and benefits.

Is the medication safe and what is the right dose?   Phase one trials involve small numbers of participants, often normal volunteers.

Does the new medication work and what are the side effects?   Phase two trials test the treatment or procedure on a larger number of participants. These participants usually have the condition or disease that the treatment is intended to remedy.

Is the new medication more effective than existing treatments?  Phase three trials have even more people enrolled. Some may get a placebo (a substance that has no medical effect) or an already approved treatment, so that the new medication can be compared to that treatment.

Is the new medication effective and safe over the long term?   Phase four happens after the treatment or procedure has been approved. Information about patients who are receiving the treatment is gathered and studied to see if any new information is seen when given to a large number of patients.

“Johns Hopkins has a comprehensive system overseeing research that is audited by the FDA and the Association for Accreditation of Human Research Protection Programs to make certain all research participants voluntarily agreed to join a study and their safety was maximized.” Gail Daumit, M.D., M.H.S., Vice Dean for Clinical Investigation, Johns Hopkins University School of Medicine

Is It Safe to Participate in Clinical Research?

There are several steps in place to protect volunteers who take part in clinical research studies. Clinical Research is regulated by the federal government. In addition, the institutional review board (IRB) and Human Subjects Research Protection Program at each study location have many safeguards built in to each study to protect the safety and privacy of participants.

Clinical researchers are required by law to follow the safety rules outlined by each study's protocol. A protocol is a detailed plan of what researchers will do in during the study.

In the U.S., every study site's IRB — which is made up of both medical experts and members of the general public — must approve all clinical research. IRB members also review plans for all clinical studies. And, they make sure that research participants are protected from as much risk as possible.

Earning Your Trust

This was not always the case. Many people of color are wary of joining clinical research because of previous poor treatment of underrepresented minorities throughout the U.S. This includes medical research performed on enslaved people without their consent, or not giving treatment to Black men who participated in the Tuskegee Study of Untreated Syphilis in the Negro Male. Since the 1970s, numerous regulations have been in place to protect the rights of study participants.

Many clinical research studies are also supervised by a data and safety monitoring committee. This is a group made up of experts in the area being studied. These biomedical professionals regularly monitor clinical studies as they progress. If they discover or suspect any problems with a study, they immediately stop the trial. In addition, Johns Hopkins Medicine’s Research Participant Advocacy Group focuses on improving the experience of people who participate in clinical research.

Clinical research participants with concerns about anything related to the study they are taking part in should contact Johns Hopkins Medicine’s IRB or our Research Participant Advocacy Group .

Learn More About Clinical Research at Johns Hopkins Medicine

For information about clinical trial opportunities at Johns Hopkins Medicine, visit our trials site.

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What are the different types of clinical research?

February 18, 2021

There are many different types of clinical research because researchers study many different things.  

Treatment research usually tests an intervention such as medication, psychotherapy, new devices, or new approaches.

Prevention research looks for better ways to prevent disorders from developing or returning. Different kinds of prevention research may study medicines, vitamins, or lifestyle changes.  

Diagnostic research refers to the practice of looking for better ways to identify a particular disorder or condition.  

Screening research aims to find the best ways to detect certain disorders or health conditions. 

Genetic studies aim to improve our ability to predict disorders by identifying and understanding how genes and illnesses may be related. Research in this area may explore ways in which a person’s genes make him or her more or less likely to develop a disorder. This may lead to development of tailor-made treatments based on a patient’s genetic make-up.  

Epidemiological studies look at how often and why disorders happen in certain groups of people.

Research studies can be outpatient or inpatient. Outpatient means that participants do not stay overnight at the hospital or research center. Inpatient means that participants will need to stay at least one night in the hospital or research center.  

Thank you for your interest in learning more about clinical research!

Research Types Explained: Basic, Clinical, Translational

“Research” is a broad stroke of a word, the verbal equivalent of painting a wall instead of a masterpiece. There are important distinctions among the three principal types of medical research — basic, clinical and translational.

Whereas basic research is looking at questions related to how nature works, translational research aims to take what’s learned in basic research and apply that in the development of solutions to medical problems. Clinical research, then, takes those solutions and studies them in clinical trials. Together, they form a continuous research loop that transforms ideas into action in the form of new treatments and tests, and advances cutting-edge developments from the lab bench to the patient’s bedside and back again.

Basic Research

When it comes to science, the “basic” in basic research describes something that’s an essential starting point. “If you think of it in terms of construction, you can’t put up a beautiful, elegant house without first putting in a foundation,” says David Frank, MD , Associate Professor of Medicine, Medical Oncology, at Dana-Farber Cancer Institute. “In science, if you don’t first understand the basic research, then you can’t move on to advanced applications.”

Basic medical research is usually conducted by scientists with a PhD in such fields as biology and chemistry, among many others. They study the core building blocks of life — DNA, cells, proteins, molecules, etc. — to answer fundamental questions about their structures and how they work.

For example, oncologists now know that mutations in DNA enable the unchecked growth of cells in cancer. A scientist conducting basic research might ask: How does DNA work in a healthy cell? How do mutations occur? Where along the DNA sequence do mutations happen? And why?

“Basic research is fundamentally curiosity-driven research,” says Milka Kostic, Program Director, Chemical Biology at Dana-Farber Cancer Institute. “Think of that moment when an apple fell on Isaac Newton’s head. He thought to himself, ‘Why did that happen?’ and then went on to try to find the answer. That’s basic research.”

Clinical Research

Clinical research explores whether new treatments, medications and diagnostic techniques are safe and effective in patients. Physicians administer these to patients in rigorously controlled clinical trials, so that they can accurately and precisely monitor patients’ progress and evaluate the treatment’s efficacy, or measurable benefit.

“In clinical research, we’re trying to define the best treatment for a patient with a given condition,” Frank says. “We’re asking such questions as: Will this new treatment extend the life of a patient with a given type of cancer? Could this supportive medication diminish nausea, diarrhea or other side effects? Could this diagnostic test help physicians detect cancer earlier or distinguish between fast- and slow-growing cancers?”

Successful clinical researchers must draw on not only their medical training but also their knowledge of such areas as statistics, controls and regulatory compliance.

Translational Research

It’s neither practical nor safe to transition directly from studying individual cells to testing on patients. Translational research provides that crucial pivot point. It bridges the gap between basic and clinical research by bringing together a number of specialists to refine and advance the application of a discovery. “Biomedical science is so complex, and there’s so much knowledge available.” Frank says. “It’s through collaboration that advances are made.”

For example, let’s say a basic researcher has identified a gene that looks like a promising candidate for targeted therapy. Translational researchers would then evaluate thousands, if not millions, of potential compounds for the ideal combination that could be developed into a medicine to achieve the desired effect. They’d refine and test the compound on intermediate models, in laboratory and animal models. Then they would analyze those test results to determine proper dosage, side effects and other safety considerations before moving to first-in-human clinical trials. It’s the complex interplay of chemistry, biology, oncology, biostatistics, genomics, pharmacology and other specialties that makes such a translational study a success.

Collaboration and technology have been the twin drivers of recent quantum leaps in the quality and quantity of translational research. “Now, using modern molecular techniques,” Frank says, “we can learn so much from a tissue sample from a patient that we couldn’t before.”

Translational research provides a crucial pivot point after clinical trials as well. Investigators explore how the trial’s resulting treatment or guidelines can be implemented by physicians in their practice. And the clinical outcomes might also motivate basic researchers to reevaluate their original assumptions.

“Translational research is a two-way street,” Kostic says. “There is always conversation flowing in both directions. It’s a loop, a continuous cycle, with one research result inspiring another.”

Learn more about research at Dana-Farber .

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Clinical Research: Benefits, Risks, and Safety

On this page:

What are the potential benefits of participating in clinical research?

What are the potential risks of participating in clinical research, will i always get the experimental treatment in a clinical trial, how is the safety of clinical research participants protected.

If you’re interested in volunteering for clinical research, you may wonder: What makes a study a good fit for me? How do I know it’s safe? Clinical research involves studying health and illness in people through observational studies or clinical trials . Participating in a trial or study has many potential benefits and also some possible risks. Learn about the benefits and risks of participating in clinical research and how your safety is protected.

There are many possible benefits of being part of clinical research, including:

• You may have the chance to help scientists better understand your disease or condition and to advance treatments and ways to prevent it in the future.
• You may feel like you’re playing a more active role in your health.
• You may learn more about your disease or condition.
• You may be able to get information about support groups and resources.

In addition, some people participate in clinical trials because they hope to gain access to a potential new treatment for a disease before it is widely available.

Clinical trials and studies do come with some possible risks, including:

• The research may involve tests that pose a risk to participants. For example, certain physical tests may increase the chance of falling, and X-rays may cause a small increase in the risk of developing cancer.
• Participating in a study could also be inconvenient for you. For example, you may be required to have additional or longer medical appointments, more procedures, complex medication instructions, or hospital stays.

Additional risks of participating in clinical trials may include:

• For those who receive the experimental treatment, it may be uncomfortable or cause side effects (which can range from mild to serious).
• The experimental treatment might not work, or it may not be better than the standard treatment.
• For trials testing a new treatment, such as a new medication or device, you may end up not being part of the group that gets the experimental treatment. Instead, you may be assigned to the control (or comparison) group. In some studies, the control group receives a placebo, which is given in the same way as the treatment but has no effect.

Participant confidentiality is a concern in any kind of research. People other than the researchers, such as the study sponsors or experts who monitor safety, may be able to access medical information related to the study. Safeguards are in place to ensure that researchers tell potential participants what information could be shared and how their privacy will be protected before they consent to participate in research.

The study coordinators will provide detailed information and answer questions about the risks and benefits of participating in a particular study. Having this information can help you make an informed decision about whether to participate.

Clinical trial volunteers do not always get the treatment being tested. The gold standard for testing interventions in people is called a randomized controlled trial. Randomized means that volunteers are randomly assigned — chosen by chance — to receive either the experimental intervention (the test group) or a placebo or the current standard care (the control or comparison group). Then, researchers compare the effects in each group to determine whether the new treatment works.

When you enroll in a clinical trial, you may be assigned to the test group or to the control group. While participants in the control group do not receive the experimental treatment, these volunteers are just as important as those in the test group. Without the control group, scientists cannot be sure whether an experimental treatment is better than the standard or no treatment.

In many cases, you won’t know until the end of the trial whether you are in the test group or the control group. That’s because knowing the group assignment might influence the results of the trial. Studies are often “blinded” (or “masked”) to prevent this accidental bias. In a single-blind study, you are not told whether you are in the test group or the control group, but the research team knows. In a double-blind study, neither you nor the research team knows what group you are in until the trial is over. If medically necessary, however, it is always possible to find out which group you are in.

What is a placebo?

Whenever possible, clinical trials compare a new treatment for a specific condition to the standard treatment for that condition. When there is no standard treatment available, scientists may compare the new treatment to a placebo, which looks like the drug or treatment being tested but isn’t meant to actually change anything in your body. A pill that doesn’t contain any medicine is one example.

A trial that uses a placebo is described as a “placebo-controlled trial.” In this type of study, the test group receives the experimental treatment, and the control group receives the placebo.

Placebos are not used if an effective treatment is already available or if you would be put at risk by not having effective therapy. You will be told if placebos are used in the study before entering a trial as part of the process of informed consent.

What happens if a clinical trial ends early?

Most clinical trials run as planned from beginning to end. However, sometimes researchers end trials early. Clinical trials may be paused or stopped for a number of reasons:

• There is clear evidence that one intervention is more effective than another. When this happens, the trial may be stopped so that the new treatment can be made available to other people as soon as possible.
• The trial shows that the treatment doesn’t work or causes unexpected and serious side effects.
• The researchers can’t enroll enough people in the trial to provide meaningful results.

Even when a clinical trial ends early, it can still provide researchers with valuable information. For example, scientists may gain insights about how to best design and conduct clinical trials in a specific research area. In some cases, health information collected during a trial can lead to new potential therapies that researchers can test in the future.

Based on many years of experience and learning from past mistakes, strict rules are in place to keep participants safe . Today, every clinical investigator in the United States is required to monitor and make sure that every participant is safe. These safeguards are an essential part of the research.

Each clinical study follows a careful study plan, called a protocol, which describes what the researchers will do. The principal investigator, or head researcher, is responsible for ensuring the protocol is followed.

Safeguards to protect clinical research volunteers include Institutional Review Boards, informed consent, Data and Safety Monitoring Boards, and Observational Study Monitoring Boards.

• Most clinical studies in the U.S. must be approved by an Institutional Review Board (IRB) . The IRB is made up of doctors, scientists, and members of the general public who ensure that the study participants are not exposed to unnecessary risks. The people on the IRB regularly review the study and its results. They make sure that risks (or potential harm) to participants do not outweigh the potential benefits of the study.
• Informed consent also helps protect participants. Informed consent is the process by which you learn the key facts about a study before deciding whether to participate. Members of the research team explain the research before you start and throughout the study. They provide an informed consent document, which includes details about the study, such as its purpose, how long it will last, required procedures, and who to contact. The informed consent document also explains risks and potential benefits. You are free to ask questions, request more information, or withdraw from the study at any time.

Clinical trials and studies also have committees that monitor the safety of the research as it occurs.

• Clinical trials that test an intervention are closely supervised by a Data and Safety Monitoring Board . The board is made up of experts who review the results of the study as it progresses. If they determine that the experimental treatment is not working or is harming participants, they can stop the trial early.
• Observational Study Monitoring Boards monitor the safety of observational studies with large or vulnerable populations, or risks associated with tests or standard of care.

Several historical incidents have caused mistrust in clinical research. These events also led to the creation of laws that provide clinical research participants with multiple levels of protection.

One example is the U.S. Public Health Service Syphilis Study at Tuskegee , which was conducted between 1932 and 1972. In this study, researchers wanted to determine the effects of untreated syphilis. They did not explain the study’s risks or obtain informed consent from the participants, all of whom were Black men. They also did not offer the study participants penicillin when it became widely available in the mid-1940s, causing preventable illness and suffering. After news of the study leaked in 1972, it led to sweeping changes in standard research practices and guidelines to protect human research participants. Today, IRBs are responsible for reviewing all studies involving humans to ensure they meet these guidelines and for reporting any study plan that breaks the rules.

After obtaining all the information, you can make an informed decision about whether or not to participate in a clinical trial or study. If you decide to volunteer for clinical research, you will be given an informed consent form to sign. By signing the form, you show that you understand the details and want to be part of the research. However, the informed consent form is not a contract. You may leave the study at any time and for any reason.

Where can I find a clinical trial or study?

Looking for clinical research related to aging and age-related health conditions? There are many ways to find a trial or study. Talk to your health care provider and use online resources to:

• Search for a clinical trial or study .
• Look for clinical trials on Alzheimer’s disease, other dementias, and caregiving .
• Find a registry for a particular diagnosis or condition .
• Explore clinical trials and studies funded by NIA .

To learn more about a particular trial or study, you or your doctor can contact the research staff and ask questions. You can usually find contact information in the study description.

You may also be interested in

• Getting more information about clinical trials and studies
• Downloading and sharing an infographic with the benefits of participating in clinical research
• Learning about participating in Alzheimer's disease research

For more information about clinical research

Clinical Research Trials and You National Institutes of Health www.nih.gov/health-information/nih-clinical-research-trials-you

ClinicalTrials.gov www.clinicaltrials.gov 

U.S. Food and Drug Administration 888-463-6332 [email protected] www.fda.gov

This content is provided by the NIH National Institute on Aging (NIA). NIA scientists and other experts review this content to ensure it is accurate and up to date.

Content reviewed: May 18, 2023

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What are the Different Types of Clinical Research?

Altus Research, based in South Florida, is a clinical research site with expertise in all phases of clinical research. But what exactly is clinical research , and what do we mean when we talk about different phases? Here is a general overview to answer these key questions.

What is Clinical Research?

Clinical research is the branch of science devoted to determining the safety and effectiveness of medical treatments, devices, and approaches. It is the testing ground for methods that later go into widespread practice in the medical field.

Types of Clinical Research

There are eight main types of clinical research, each differing in its purpose and principal goals.

Treatment Research

This type of research focuses on developing new medical treatments, including novel medications or psychotherapy. It also involves testing new devices or medical approaches.

Prevention Research

This research focuses not on curing diseases and health problems, but on how they can be prevented in the first place.

Screening Research

These studies explore the effectiveness of novel methods of detecting the presence of disorders in the human body.

Diagnostic Research

Once problems have been detected, they must be properly identified (diagnosed) before treatment options can be considered. Diagnostic research focuses on how this identification process can best be completed.

Genetic Studies

Recent research suggests that the study of genetics might be a game-changer in the medical field, allowing professionals to identify a person as being at-risk for a particular disease, and then treat that disease according to the individual’s genetic make-up. The field of genetic studies focuses on how this can be done effectively.

Epidemiological Studies

This branch of research focuses on patterns of disorders within populations, seeking the causes of epidemics and studying how they can be controlled.

Quality of Life Research

Beyond prevention or treatment, this type of research explores how life can be made better for those with a chronic illness.

Phases of Clinical Trials

A typical clinical trial includes four distinct phases , each of which provides researchers with pivotal information about the drug or treatment in question.

The first phase of a clinical trial involves testing the drug or treatment on a small number of people, then watching for safety, side effects and the ideal dosages.

In the second phase, a larger number of people are given the treatment, and researchers again check for side effects and safety.

The third phase sees the drug or treatment administered to very large groups of people, giving researchers a chance to observe a vast array of cases and monitor for safety, side effects, and effectiveness while comparing the treatment to other common methods.

The final phase of a clinical trial occurs after the drug or treatment has been approved by the FDA, and consists of post-marketing studies on side effects and effectiveness.

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Step 3: Clinical Research

While preclinical research answers basic questions about a drug’s safety, it is not a substitute for studies of ways the drug will interact with the human body. “Clinical research” refers to studies, or trials, that are done in people. As the developers design the clinical study, they will consider what they want to accomplish for each of the different Clinical Research Phases and begin the Investigational New Drug Process (IND), a process they must go through before clinical research begins.

On this page you will find information on:

Designing Clinical Trials

Clinical Research Phase Studies

The Investigational New Drug Process

Asking for FDA Assistance

FDA IND Review Team

Researchers design clinical trials to answer specific research questions related to a medical product. These trials follow a specific study plan, called a protocol , that is developed by the researcher or manufacturer. Before a clinical trial begins, researchers review prior information about the drug to develop research questions and objectives. Then, they decide:

Who qualifies to participate (selection criteria)

How many people will be part of the study

How long the study will last

Whether there will be a control group and other ways to limit research bias

How the drug will be given to patients and at what dosage

What assessments will be conducted, when, and what data will be collected

How the data will be reviewed and analyzed

Clinical trials follow a typical series from early, small-scale, Phase 1 studies to late-stage, large scale, Phase 3 studies.

What are the Clinical Trial Phases?

Watch this video to learn about the three phases of clinical trials.

Study Participants: 20 to 100 healthy volunteers or people with the disease/condition.

Length of Study: Several months

Purpose: Safety and dosage

During Phase 1 studies, researchers test a new drug in normal volunteers (healthy people). In most cases, 20 to 80 healthy volunteers or people with the disease/condition participate in Phase 1. However, if a new drug is intended for use in cancer patients, researchers conduct Phase 1 studies in patients with that type of cancer.

Phase 1 studies are closely monitored and gather information about how a drug interacts with the human body. Researchers adjust dosing schemes based on animal data to find out how much of a drug the body can tolerate and what its acute side effects are.

As a Phase 1 trial continues, researchers answer research questions related to how it works in the body, the side effects associated with increased dosage, and early information about how effective it is to determine how best to administer the drug to limit risks and maximize possible benefits. This is important to the design of Phase 2 studies.

Approximately 70% of drugs move to the next phase

Study Participants: Up to several hundred people with the disease/condition.

Length of Study: Several months to 2 years

Purpose: Efficacy and side effects

In Phase 2 studies, researchers administer the drug to a group of patients with the disease or condition for which the drug is being developed. Typically involving a few hundred patients, these studies aren't large enough to show whether the drug will be beneficial.

Instead, Phase 2 studies provide researchers with additional safety data. Researchers use these data to refine research questions, develop research methods, and design new Phase 3 research protocols.

Approximately 33% of drugs move to the next phase

Study Participants: 300 to 3,000 volunteers who have the disease or condition

Length of Study: 1 to 4 years

Purpose: Efficacy and monitoring of adverse reactions

Researchers design Phase 3 studies to demonstrate whether or not a product offers a treatment benefit to a specific population. Sometimes known as pivotal studies, these studies involve 300 to 3,000 participants.

Phase 3 studies provide most of the safety data. In previous studies, it is possible that less common side effects might have gone undetected. Because these studies are larger and longer in duration, the results are more likely to show long-term or rare side effects

Approximately 25-30% of drugs move to the next phase

Study Participants: Several thousand volunteers who have the disease/condition

Purpose: Safety and efficacy

Phase 4 trials are carried out once the drug or device has been approved by FDA during the Post-Market Safety Monitoring

Learn more about Clinical Trials .

Drug developers, or sponsors , must submit an Investigational New Drug (IND) application to FDA before beginning clinical research.

In the IND application, developers must include:

Animal study data and toxicity (side effects that cause great harm) data

Manufacturing information

Clinical protocols (study plans) for studies to be conducted

Data from any prior human research

Information about the investigator

Drug developers are free to ask for help from FDA at any point in the drug development process, including:

Pre-IND application, to review FDA guidance documents and get answers to questions that may help enhance their research

After Phase 2, to obtain guidance on the design of large Phase 3 studies

Any time during the process, to obtain an assessment of the IND application

Even though FDA offers extensive technical assistance, drug developers are not required to take FDA’s suggestions. As long as clinical trials are thoughtfully designed, reflect what developers know about a product, safeguard participants, and otherwise meet Federal standards, FDA allows wide latitude in clinical trial design.

The review team consists of a group of specialists in different scientific fields. Each member has different responsibilities.

Project Manager: Coordinates the team’s activities throughout the review process, and is the primary contact for the sponsor.

Medical Officer: Reviews all clinical study information and data before, during, and after the trial is complete.

Statistician: Interprets clinical trial designs and data, and works closely with the medical officer to evaluate protocols and safety and efficacy data.

Pharmacologist: Reviews preclinical studies.

Pharmakineticist: Focuses on the drug’s absorption, distribution, metabolism, and excretion processes.Interprets blood-level data at different time intervals from clinical trials, as a way to assess drug dosages and administration schedules.

Chemist: Evaluates a drug’s chemical compounds. Analyzes how a drug was made and its stability, quality control, continuity, the presence of impurities, etc.

Microbiologist: Reviews the data submitted, if the product is an antimicrobial product, to assess response across different classes of microbes.

The FDA review team has 30 days to review the original IND submission. The process protects volunteers who participate in clinical trials from unreasonable and significant risk in clinical trials. FDA responds to IND applications in one of two ways:

Approval to begin clinical trials.

Clinical hold to delay or stop the investigation. FDA can place a clinical hold for specific reasons, including:

Participants are exposed to unreasonable or significant risk.

Investigators are not qualified.

Materials for the volunteer participants are misleading.

The IND application does not include enough information about the trial’s risks.

A clinical hold is rare; instead, FDA often provides comments intended to improve the quality of a clinical trial. In most cases, if FDA is satisfied that the trial meets Federal standards, the applicant is allowed to proceed with the proposed study.

The developer is responsible for informing the review team about new protocols, as well as serious side effects seen during the trial. This information ensures that the team can monitor the trials carefully for signs of any problems. After the trial ends, researchers must submit study reports.

This process continues until the developer decides to end clinical trials or files a marketing application. Before filing a marketing application, a developer must have adequate data from two large, controlled clinical trials.

Research Methods Resources

Methods at a glance.

This section provides information and examples of methodological issues to be aware of when working with different study designs. Virtually all studies face methodological issues regarding the selection of the primary outcome(s), sample size estimation, missing outcomes, and multiple comparisons. Randomized studies face additional challenges related to the method for randomization. Other studies face specific challenges associated with their study design such as those that arise in effectiveness-implementation research; multiphase optimization strategy (MOST) studies; sequential, multiple assignment, randomized trials (SMART); crossover designs; non-inferiority trials; regression discontinuity designs; and paired availability designs. Some studies face issues involving exact tests, adherence to behavioral interventions, noncompliance in encouragement designs, evaluation of risk prediction models, or evaluation of surrogate endpoints.

Learn more about broadly applicable methods

Experiments, including clinical trials, differ considerably in the methods used to assign participants to study conditions (or study arms) and to deliver interventions to those participants.

This section provides information related to the design and analysis of experiments in which 

• participants are assigned in groups (or clusters) and individual observations are analyzed to evaluate the effect of the intervention, 
• participants are assigned individually but receive at least some of their intervention with other participants or through an intervention agent shared with other participants,
• participants are assigned in groups (or clusters) but groups cross over to the intervention condition at pre-determined time points in sequential, staggered fashion until all groups receive the intervention, and
• participants are assigned in groups, which are assigned to receive the intervention based on a cutoff value of some score value, and individual observations are used to evaluate the effect of the intervention.

This material is relevant for both human and animal studies as well as basic and applied research. And while it is important for investigators to become familiar with the issues presented on this website, it is even more important that they collaborate with a methodologist who is familiar with these issues.

In a parallel group-randomized trial (GRT), groups or clusters are randomized to study conditions, and observations are taken on the members of those groups with no crossover to a different condition during the trial.

Learn more about GRTs

In an individually randomized group-treatment (IRGT) trial, individuals are randomized to study conditions but receive at least some of their intervention with other participants or through an intervention agent shared with other participants.

Learn more about IRGTs

In a stepped wedge group- or cluster-randomized trial (SWGRT), groups or clusters are randomized to sequences that cross over to the intervention condition at predetermined time points in a staggered fashion until all groups receive the intervention.

Learn more about SWGRTs

In a group or cluster regression discontinuity design (GRDD), groups or clusters are assigned to study conditions if a group-level summary crosses a cut-off defined by an assignment score. Observations are taken on members of the groups.

Learn more about GRDDs

NIH Clinical Trial Requirements

The NIH launched a series of initiatives to enhance the accountability and transparency of clinical research. These initiatives target key points along the entire clinical trial lifecycle, from concept to reporting the results.

Check out the  Frequently Asked Questions  section or send us a message . 

Disclaimer: Substantial effort has been made to provide accurate and complete information on this website. However, we cannot guarantee that there will be no errors. Neither the U.S. Government nor the National Institutes of Health (NIH) assumes any legal liability for the accuracy, completeness, or usefulness of any information, products, or processes disclosed herein, or represents that use of such information, products, or processes would not infringe on privately owned rights. The NIH does not endorse or recommend any commercial products, processes, or services. The views and opinions of authors expressed on NIH websites do not necessarily state or reflect those of the U.S. Government, and they may not be used for advertising or product endorsement purposes.

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Master of Science

Clinical research methods.

The Clinical Research Methods (CRM) track in Biostatistics responds to a pressing need for advanced training in clinical research design and analysis. As medical school curricula become increasingly full and apprenticeship prospects wane, pathways to becoming a clinical researcher have narrowed. This program offers talented-but-novice investigators who already have a doctoral degree a chance to master the basic principles and scientific methods essential for conducting human research studies.

The 30-credit program can be completed within one year if initiated during the summer semester. Part-time students must complete the degree in five years. Throughout their course of study, CRM students receive formal, rigorous training in skills that are critical to the design and analysis of research studies involving human subjects.

Admissions Information

Applicants to the program must hold a doctoral degree in a clinical discipline or public health field. Recent applicants have included physicians, nurses, dentists, pharmacists, and other healthcare professionals who desire careers or are actively engaged in clinical research. An applicant's undergraduate training should include a one-semester course in calculus.

Applications are due on April 1st of each calendar year, to begin studies the following summer or fall, and include transcripts from college and graduate school, a curriculum vitae, a personal statement detailing the applicant's reasons for seeking clinical research training, and three letters of reference.

View competencies, course requirements, sample schedules, and more  in our Academics section. 

Search the Columbia Directory  to find current students in the program. 

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Topics: Clinical & Translational Research , Five Questions

How to Accelerate Clinical Research

Five questions with michelle beck and yemi talabi-oates on making connections..

At Brigham and Women’s Hospital (BWH), oncologists who’ve been doing gene therapy trials for a decade are teaming up with researchers in other fields to apply their knowledge to the new wave of non-oncology cell and gene therapy studies and avoid recreating the wheel.

And at Beth Israel Deaconess Medical Center (BIDMC), one researcher’s challenges enrolling Black patients for a diet intervention study led to the development of a satellite center at a community-based clinic, which other researchers are exploring for their own studies.

These are among the ways Harvard Catalyst’s Connector sites facilitate and accelerate clinical/translational research across the hospitals affiliated with Harvard Medical School (HMS). Connector links investigators to the medical centers’ sprawling clinical research enterprises and troubleshoots research bottlenecks. (Boston Children’s Hospital and Mass General Hospital also have Connector sites.)

Need a research problem solved?

The premise behind Connector is that clinical research can be challenging, especially in complex academic healthcare environments. Individual scientists can’t do it alone. Connector sites help researchers get science done right–hopefully the first time–while maintaining the highest standards for patient protection, regulatory compliance, and quality.

Connector draws upon the collective expertise of HMS-affiliated institutions to guide studies through the lifecycle of science. For investigators struggling to recruit or wrestling with logistics, the programs offer a kind of life-raft of resources and support, big or small.

As the administrative directors of Connector sites at BIDMC and BWH, respectively, Michelle Beck and Yemi Talabi-Oates are like the Ghostbusters of translational research: They are “who you gonna call” when you’ve got a research problem to solve.

We caught up with them both in one Zoom to find out what they wish investigators knew about Connector.

What’s your cocktail-party summary of what Connector is?

MB: A cocktail-party summary is hard because Connector does a bit of everything, depending on what the investigator wants. Connector sites are really good at figuring out how to set studies up. Our special sauce, so to speak, is the experience in knowing how to make things work.

“Connector sites are really good at figuring out how to set studies up. Our special sauce, so to speak, is the experience in knowing how to make things work.”

At BIDMC, Connector encompasses our Clinical Research Center, a full-service operation providing research coordination and personnel for the lifecycle of a study, including recruitment. We provide laboratory, dietary, specialized nursing–because research nursing is a little different than clinical care nursing–and all affiliated services for inpatients and outpatients in our own research space as well as in other locations.

We help research teams get the tools and resources they need in other parts of BIDMC or across the network of HMS-affiliated hospitals. We might refer them elsewhere or integrate their research into our portfolio.

YTO: Brigham’s version of the Connector is the Center for Clinical Investigation (CCI). We call ourselves the home of clinical research. We are the first stop if an investigator needs help or wants to learn how to implement clinical and translational research studies.

Investigators can use any or all of our resources, from something small to running the whole study. We can connect them with potential collaborators or just find somebody to read an EKG, if that’s what’s needed.

We have clinical space dedicated to research so we can accommodate patient visits. But just as importantly, investigators have access to vital services that are not patient-facing, such as data management, research coordination, and biostatistics support.

What do you wish investigators knew about Connector?

MB: People sometimes think that Connector is the CRC. While it is at some level, it’s also much more. Our strength lies in the collective experience of the many people who have already figured out how to design and conduct high-quality studies, who understand the steps for getting from point A to point B.

Our program director regularly meets with investigators to provide feedback on their grant applications, offer advice on how to find funding, or connect them with mentors.

All of the Connector sites have a role called a navigator. BIDMC navigators are experts in regulatory and operations. Depending on when they’re brought in, they can point investigators to resources or work through specific aspects of their study that might be challenging.

YTO: What I find with investigators is they don’t know what they don’t know. They may come to us with one question and not realize how many other things need to be considered before we can address that one question. Having that dialogue as early in the process as possible will help the investigator in the end.

Connector lets investigators tap the experience of a diverse clinical research team, whether it’s the nurses on the floor or a physician-investigator who’s done this before. It’s about knowing your patient population and what works with recruiting, right down to which time of day is easier for patients. It’s helping avoid the pitfalls that may come with being a newbie to research.

“Connector lets investigators tap the experience of a diverse clinical research team, whether it’s the nurses on the floor or a physician-investigator who’s done this before. It’s helping avoid the pitfalls that may come with being a newbie to research.”

One of the things I often say to early-career investigators or those testing a really novel idea is if you’re going to fail, fail fast. It’s okay to fail because you can use what you learn to make the next study better.

Give us an example of something you’re engaged in right now that illustrates how the Connector sites work.

YTO: One of our big pushes right now is to help investigators in the non-oncology space who are interested in conducting cell and gene therapy studies. We don’t want to recreate the wheel, so we’re connecting them to oncology physicians who have been doing these studies for a while. We’re bringing together players who aren’t otherwise talking to one another to figure out how current systems might be adapted for studies outside of oncology.

MB: We have a general medicine investigator who is running a diet intervention study for hypertension, focusing on enrolling Black Boston residents in areas with ‘food deserts’ –areas with grocery store scarcity. This investigator met with our Connector team early in his grant planning process. His studies are now funded, and he’s running them through our main Clinical Research Center at the Boston campus. But he is having a really hard time meeting his recruitment goals, so we are working with him to set up research support at our Bowdoin Street clinic.

Because of that collaboration, the clinic is being developed as a CRC satellite with a focus on community-engaged research that allows the local community to provide input on the studies conducted there. We are now working with other clinical groups to expand research at the site.

So by addressing a recruitment problem one investigator was having, we’re establishing a resource that other investigators can access to bring research to our community and potentially improve participant diversity in their studies.

Connector’s goal is to accelerate translational science, in line with the mission of Harvard Catalyst and other clinical and translational science programs funded by the National Center for Clinical and Translational Science (NCATS). From your perspective, is clinical research efficient enough?

MB: I think sometimes we have unrealistic expectations about efficiency. I honestly believe that we make things very efficient in our programs and within our institutions, but I don’t think clinical research itself is efficient, through no fault of our own.

It’s really difficult to run a study, especially if you think about the whole lifecycle. For an industry-initiated clinical trial for example, a sponsor wants you to have a budget, contract, IRB approval, and be ready to enroll your first patient within 60 days of being selected as a site, which is crazy. It’s not impossible but it’s highly unlikely, with so many steps and the complexity of various studies.

If you move too fast, you risk making mistakes. If you don’t think carefully about what’s involved in a study from a participant’s perspective, for example, you might meet your recruitment goals right away but have 60% who don’t meet inclusion/exclusion criteria at screening and 20% who didn’t realize they’d have to come in every day for the next six weeks. Those kinds of circumstances can be largely avoided with the right planning.

YTO: We definitely take some time on the front end to get all the information and tweak things where necessary to make sure the patient’s experience and the study team’s experience is positive and efficient. We want to make sure it’s done right, and that might take a little longer.

In the end I’d rather be confident that patients are safe and the data is accurate because we thought these things through up-front. That’s the time to do it, not when the patient shows up for the visit or the investigator sits down to write that paper with flawed data.

How does Connector affect the experience of patients involved in clinical research and why does that matter?

MB: Using a Clinical Research Center is hugely beneficial from the participant perspective. We had a study many years ago in which two people came in every month for seven years for the same study. They got to know each other, and they knew all our staff; they would even bake banana bread for the research center staff. I think if patients get to know the research center, that’s another mechanism for patient retention, particularly for longitudinal studies.

YTO: Agreed. Our nurses and clinical staff on the floor definitely make connections with the research participants, and they often learn something that could be valuable to the study team. Having that connection is key.

It’s not just the study team; it’s every member of the staff. It’s the person who smiles when they walk in the door, or the one who knows about their child or their cat and asks about it. That matters when you want a patient to come back again and again into the next month or year.

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• Clinical trials and evidence

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Alternatives to Animal Testing Models in Clinical and Biomedical Research

Over the past several years, a growing number of alternative techniques have been developed and used to replace animal testing models in clinical and biomedical research..

• Alivia Kaylor, MSc

Before the FDA Modernization Act 2.0 was passed in December 2022, the US government required that all investigational drugs be tested on animals before they could advance to human trials. Although this act does not ban animal testing, it allows researchers to use scientifically proven, non-animal testing methods, such as cell-based assays, microfluidic chips, tissue models, computer models, and human volunteers, when possible.

Animal Testing

Animal testing models have been used throughout history, dating back to 500 BC in ancient Greece. Researching animals is essential for translating discoveries and observations in the laboratory or clinic into new treatments.

Today, standard animal models usually include mice and rats due to their anatomical, genetic, and physiological similarity to humans and their ease of maintenance and size, short life cycle, and abundant genetic resources.

In several research fields, non-human primates (NHPs) — a group of hominins, apes, and monkeys that are biologically and evolutionally similar to humans — are used for scientific, educational, and exhibition purposes. Because NHPs have short life spans and are susceptible to many of the same health conditions that affect humans, they serve as ideal research subjects for studying entire life cycles or several generations.

NHPs are vital for researching a wide array of diseases:

• central nervous system diseases (Alzheimer’s, Parkinson’s, and Huntington’s)
• cancer (liver, renal, gastric)
• metabolic disorders (diabetes and obesity)
• cardiovascular diseases (atherosclerosis and cardiac arrhythmias)
• infectious diseases (HIV/AIDS, malaria, SARS, COVID-19)
• ocular diseases (dry eyes, cataract glaucoma, age-related macular degeneration)
• reproductive conditions (endometriosis, polycystic ovarian syndrome, pelvic inflammatory diseases)

However, as NHP suppliers struggle to meet an unprecedented surge in global demand to study these types of diseases, research institutions have found it increasingly challenging to obtain NHPs in the past several months.

Animal Welfare

Although federal organizations have developed clinical laws and regulations — such as the  Animal Welfare Act  (AWA) and its succeeding policies — to regulate the treatment of research animals, this practice has been under intense scrutiny by animal rights advocates and policymakers for decades.

According to AWA regulations, principal investigators (PIs) must seek alternatives to painful or distressing procedures. If no other options are viable, researchers must submit a written notice to their Institutional Animal Care and Use Committee (IACUC) that outlines how the team determined that there are no alternatives available. To take it a step further, PIs must also supply written assurance that their research activities do not duplicate prior experiments unnecessarily.

While animal testing has helped humans advance our scientific understanding and develop new medicines and treatments, some experts who study animal testing argue that it can be expensive and ineffective.

“We have many important drugs that have been developed using animal tests. But as we get into some of these more difficult diseases, especially neurological diseases, the animal models aren't serving us as well,” Paul Locke, MPH, JD, DrPH, a scientist and lawyer at Johns Hopkins University, told Wired . “Researchers need new ways to unlock the molecular mechanisms causing these diseases, and the alternatives hold great promise.”

Advocates like Locke highlight studies that demonstrate animal testing can be an  unreliable predictor of toxicity  in the human body. For example, fialuridine , a drug developed for treating hepatitis B, causes liver failure and is toxic to humans but not mice.

Because  90% of general drug candidates in clinical trials never reach the market , drugs that target the brain typically have an  even higher failure rate . These proven inconsistencies and associated time, cost, and ethical concerns have encouraged scientists to develop alternative testing methods that better recapitulate human physiology. 

What Are Alternatives to Animal Testing?

Using alternatives to animal testing in clinical research when suitable does not put patients at risk or delay medical progress. Instead, non-animal testing methods such as human cell- and tissue-based testing, human volunteer testing, and computational and mathematical models can be more accurate, cost-effective, and quicker than traditional animal models.

Human Cell- and Tissue-Based Testing

Miniature cellular and tissue models, such as organs-on-a-chip and 3D bioprinting , use human cells to mimic organ functions and structures to screen treatments and test drugs. This allows researchers to simplify a system, limiting the number of variables. Instead of animals, these human-based models can be used to study biological and disease processes and drug metabolism.

Organs-on-a-Chip

Microfluidic organs-on-a-chip are small, clear, flexible polymer devices that comprise human cells and push fluid through tiny channels to imitate blood flow. In 2010, a team at Harvard University’s Wyss Institute developed the first successful human-cell chip. The first of its kind, the lung-on-a-chip, carried out basic lung functions, like respiration. And now, researchers have expanded upon this concept by successfully creating chips that mimic the liver, stomach, intestine, brain, and skin, among others.

Because roughly 30% of medications fail in human clinical trials due to toxicity — despite pre-clinical data using animal and cell models — tissue chips function as new human cell-based approaches that help researchers accurately determine how effective a therapeutic candidate would be in clinical studies.

By eliminating toxic or ineffective drugs earlier in development, drug manufacturers can save valuable time and money. These chips also could teach scientists a great deal about disease progression, leading to better prevention, diagnosis, and treatment approaches.

Because many industry experts recognize the widespread benefits of human-specific chips, this method is becoming popular in drug discovery and development.

Organs-on-a-chip technology allows scientists to easily replicate human tissue and organ functions to assess the safety and efficacy of new drugs. For instance, the Liver-Chip, a liver-on-a-chip device , can detect drug-induced liver injury missed by animal testing models.

Tissue Bioprinting

Three-dimensional (3D) tissue bioprinting is a revolutionary scientific advancement in drug discovery and development that uses new assay models to predict drug impacts on humans better. These tissue models mimic characteristics of live human tissues and are developed on microplates to test the toxicity and efficacy of small molecules or other therapeutics.

By leveraging tissue engineering, stem cell research, disease biology, and in situ  detection devices for tissue characterization and drug development, 3D tissue bioprinting produces disease-relevant tissue models that can reduce the predictability gap between the results from current 2D cell-based assays and the results from testing in humans.

Human Volunteer Testing

Thanks to numerous technological advances, new and sophisticated scanning devices and recording methods can now be used to study human volunteers safely.

For example, advancements in brain imaging techniques allow researchers to see inside the brain to monitor the progression and treatment of certain brain diseases. Researchers use these approaches to better understand diseases by comparing their results with the results of healthy volunteers.

In other research areas, such as nutrition, substance use, and pain management, consenting humans can help replace animal testing models. Compared to animal subjects, human volunteers provide a significant advantage by having the ability to speak with researchers and offer additional information during the study.

As opposed to animal testing, human volunteers that donate healthy and compromised tissues via surgery provide a more appropriate way of studying human biology and disease. For example, skin and eye models made from reconstituted human skin and other tissues have been developed to replace rabbit irritation tests.

By donating tissue, alive and deceased donors increase the number of human samples available for research and reduce the number of animal subjects needed. In the past, post-mortem brain tissue has provided important breakthroughs in understanding brain regeneration and the effects of multiple sclerosis and Parkinson’s disease.

Computational and Mathematical Models

With the growing capabilities of computers and computer programs, the ability to model certain aspects of the human body has become easier than ever.

Current computer models of the heart, lungs, kidneys, skin, and digestive and musculoskeletal systems have been developed to conduct virtual experiments based on existing mathematical data and information. Additionally, data mining tools assist researchers in making predictions about one substance based on existing data from similar substances.

Many alternatives to animal testing methods aim to overcome translational barriers toward developing urgently needed treatments for unmet medical needs. As a result, using non-animal models for research could save the lives of more humans and animals, time, and money. And without sacrificing quality and safety, alternatives to animal testing could improve the quality of society while improving health outcomes.

• The Fundamentals of Animal Testing in Clinical Research
• Understanding the Value, Complexity of Clinical Trials in the US
• How Brain-in-a-Dish Technology Can Impact the Treatment of MDD

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COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK

Clinical Research Coordinator

• Herbert Irving Comprehensive Cancer Center
• Columbia University Medical Center
• Opening on: Aug 20 2024
• Job Type: Officer of Administration
• Bargaining Unit:
• Regular/Temporary: Regular
• End Date if Temporary:
• Hours Per Week: 35
• Standard Work Schedule:
• Salary Range: $62,400 - $65,000

Position Summary

The Clinical Research Coordinator manages clinical trials conducted through the Clinical Protocol & Data Management Office. This position reports directly to the Clinical Research Manager of the specific disease site this incumbent is assigned to. The Clinical Research Coordinator manages clinical trials (including some regulatory and budget requirements) and assists in the coordination of tests/visits for patients, working with the study team to maximize work efficiency to gather all required data and relevant clinical information.

Subject to business needs, we may support flexible and hybrid work arrangements. Options will be discussed during the interview process.

Responsibilities

Responsibilities include, but are not limited to:

GENERAL STUDY MANAGEMENT

• Reviewing research protocols
• Assisting Principal Investigators in drafting budgets and submitting studies
• Interacting with the regulatory office to maintain regulatory documentation and administrative files for each protocol
• Under the supervision of the clinical research management office supervisor, the coordinator maintains procedures necessary for timely and complete data management and complies with required supervision tools such as work logs and regular meetings.
• The coordinator will also comply with necessary regulatory responsibilities

PATIENT MANAGEMENT

• Coordinates study enrollment, protocol treatment, and follow-up care for patients participating in clinical trials in conjunction with the clinical research nurse, research pharmacy, treatment center, and other study staff
• Working with the research nurse, treating physicians, and Principal Investigators to confirm that each patient meets eligibility criteria specified for protocols and enrollment into clinical trials
• Communicating with various departments, physicians, labs, outside hospitals, and all members of the clinical team to ensure accuracy, timely retrieval of data, and confirm the appropriateness and timeliness of tests
• Collecting follow-up data on patient post-treatment as required by the protocol and submit monthly reports to the clinical protocol office, tracking patient enrollment and accounts/payments for sponsored protocols
• Completes timely research billing review
• Maintains and updates sponsor-related, university and department databases/logs

DATA MANAGEMENT

• Handling data management requirements for each patient enrolled
• Abstracts, assembles, and organizes clinical research data
• Coordinator performs other related duties and participates in special projects as assigned

Minimum Qualifications

• Bachelor’s Degree or equivalent in education, training, and experience.

Preferred Qualifications

• Experience in a clinical research setting with knowledge of HIPAA and GCP.

Other Requirements

• Excellent interpersonal and organizational skills.
• Computer Skills: proficiency with MS Word programs and familiarity with Mac and PC platforms.

Equal Opportunity Employer / Disability / Veteran

Columbia University is committed to the hiring of qualified local residents.

Commitment to Diversity 

Columbia university is dedicated to increasing diversity in its workforce, its student body, and its educational programs. achieving continued academic excellence and creating a vibrant university community require nothing less. in fulfilling its mission to advance diversity at the university, columbia seeks to hire, retain, and promote exceptionally talented individuals from diverse backgrounds.  , share this job.

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• v.11(2); 2019 Feb

Planning and Conducting Clinical Research: The Whole Process

Boon-how chew.

1 Family Medicine, Universiti Putra Malaysia, Serdang, MYS

The goal of this review was to present the essential steps in the entire process of clinical research. Research should begin with an educated idea arising from a clinical practice issue. A research topic rooted in a clinical problem provides the motivation for the completion of the research and relevancy for affecting medical practice changes and improvements. The research idea is further informed through a systematic literature review, clarified into a conceptual framework, and defined into an answerable research question. Engagement with clinical experts, experienced researchers, relevant stakeholders of the research topic, and even patients can enhance the research question’s relevance, feasibility, and efficiency. Clinical research can be completed in two major steps: study designing and study reporting. Three study designs should be planned in sequence and iterated until properly refined: theoretical design, data collection design, and statistical analysis design. The design of data collection could be further categorized into three facets: experimental or non-experimental, sampling or census, and time features of the variables to be studied. The ultimate aims of research reporting are to present findings succinctly and timely. Concise, explicit, and complete reporting are the guiding principles in clinical studies reporting.

Introduction and background

Medical and clinical research can be classified in many different ways. Probably, most people are familiar with basic (laboratory) research, clinical research, healthcare (services) research, health systems (policy) research, and educational research. Clinical research in this review refers to scientific research related to clinical practices. There are many ways a clinical research's findings can become invalid or less impactful including ignorance of previous similar studies, a paucity of similar studies, poor study design and implementation, low test agent efficacy, no predetermined statistical analysis, insufficient reporting, bias, and conflicts of interest [ 1 - 4 ]. Scientific, ethical, and moral decadence among researchers can be due to incognizant criteria in academic promotion and remuneration and too many forced studies by amateurs and students for the sake of research without adequate training or guidance [ 2 , 5 - 6 ]. This article will review the proper methods to conduct medical research from the planning stage to submission for publication (Table ​ (Table1 1 ).

a Feasibility and efficiency are considered during the refinement of the research question and adhered to during data collection.

Epidemiologic studies in clinical and medical fields focus on the effect of a determinant on an outcome [ 7 ]. Measurement errors that happen systematically give rise to biases leading to invalid study results, whereas random measurement errors will cause imprecise reporting of effects. Precision can usually be increased with an increased sample size provided biases are avoided or trivialized. Otherwise, the increased precision will aggravate the biases. Because epidemiologic, clinical research focuses on measurement, measurement errors are addressed throughout the research process. Obtaining the most accurate estimate of a treatment effect constitutes the whole business of epidemiologic research in clinical practice. This is greatly facilitated by clinical expertise and current scientific knowledge of the research topic. Current scientific knowledge is acquired through literature reviews or in collaboration with an expert clinician. Collaboration and consultation with an expert clinician should also include input from the target population to confirm the relevance of the research question. The novelty of a research topic is less important than the clinical applicability of the topic. Researchers need to acquire appropriate writing and reporting skills from the beginning of their careers, and these skills should improve with persistent use and regular reviewing of published journal articles. A published clinical research study stands on solid scientific ground to inform clinical practice given the article has passed through proper peer-reviews, revision, and content improvement.

Systematic literature reviews

Systematic literature reviews of published papers will inform authors of the existing clinical evidence on a research topic. This is an important step to reduce wasted efforts and evaluate the planned study [ 8 ]. Conducting a systematic literature review is a well-known important step before embarking on a new study [ 9 ]. A rigorously performed and cautiously interpreted systematic review that includes in-process trials can inform researchers of several factors [ 10 ]. Reviewing the literature will inform the choice of recruitment methods, outcome measures, questionnaires, intervention details, and statistical strategies – useful information to increase the study’s relevance, value, and power. A good review of previous studies will also provide evidence of the effects of an intervention that may or may not be worthwhile; this would suggest either no further studies are warranted or that further study of the intervention is needed. A review can also inform whether a larger and better study is preferable to an additional small study. Reviews of previously published work may yield few studies or low-quality evidence from small or poorly designed studies on certain intervention or observation; this may encourage or discourage further research or prompt consideration of a first clinical trial.

Conceptual framework

The result of a literature review should include identifying a working conceptual framework to clarify the nature of the research problem, questions, and designs, and even guide the latter discussion of the findings and development of possible solutions. Conceptual frameworks represent ways of thinking about a problem or how complex things work the way they do [ 11 ]. Different frameworks will emphasize different variables and outcomes, and their inter-relatedness. Each framework highlights or emphasizes different aspects of a problem or research question. Often, any single conceptual framework presents only a partial view of reality [ 11 ]. Furthermore, each framework magnifies certain elements of the problem. Therefore, a thorough literature search is warranted for authors to avoid repeating the same research endeavors or mistakes. It may also help them find relevant conceptual frameworks including those that are outside one’s specialty or system. 

Conceptual frameworks can come from theories with well-organized principles and propositions that have been confirmed by observations or experiments. Conceptual frameworks can also come from models derived from theories, observations or sets of concepts or even evidence-based best practices derived from past studies [ 11 ].

Researchers convey their assumptions of the associations of the variables explicitly in the conceptual framework to connect the research to the literature. After selecting a single conceptual framework or a combination of a few frameworks, a clinical study can be completed in two fundamental steps: study design and study report. Three study designs should be planned in sequence and iterated until satisfaction: the theoretical design, data collection design, and statistical analysis design [ 7 ]. 

Study designs

Theoretical Design

Theoretical design is the next important step in the research process after a literature review and conceptual framework identification. While the theoretical design is a crucial step in research planning, it is often dealt with lightly because of the more alluring second step (data collection design). In the theoretical design phase, a research question is designed to address a clinical problem, which involves an informed understanding based on the literature review and effective collaboration with the right experts and clinicians. A well-developed research question will have an initial hypothesis of the possible relationship between the explanatory variable/exposure and the outcome. This will inform the nature of the study design, be it qualitative or quantitative, primary or secondary, and non-causal or causal (Figure ​ (Figure1 1 ).

A study is qualitative if the research question aims to explore, understand, describe, discover or generate reasons underlying certain phenomena. Qualitative studies usually focus on a process to determine how and why things happen [ 12 ]. Quantitative studies use deductive reasoning, and numerical statistical quantification of the association between groups on data often gathered during experiments [ 13 ]. A primary clinical study is an original study gathering a new set of patient-level data. Secondary research draws on the existing available data and pooling them into a larger database to generate a wider perspective or a more powerful conclusion. Non-causal or descriptive research aims to identify the determinants or associated factors for the outcome or health condition, without regard for causal relationships. Causal research is an exploration of the determinants of an outcome while mitigating confounding variables. Table ​ Table2 2 shows examples of non-causal (e.g., diagnostic and prognostic) and causal (e.g., intervention and etiologic) clinical studies. Concordance between the research question, its aim, and the choice of theoretical design will provide a strong foundation and the right direction for the research process and path. 

A problem in clinical epidemiology is phrased in a mathematical relationship below, where the outcome is a function of the determinant (D) conditional on the extraneous determinants (ED) or more commonly known as the confounding factors [ 7 ]:

For non-causal research, Outcome = f (D1, D2…Dn) For causal research, Outcome = f (D | ED)

A fine research question is composed of at least three components: 1) an outcome or a health condition, 2) determinant/s or associated factors to the outcome, and 3) the domain. The outcome and the determinants have to be clearly conceptualized and operationalized as measurable variables (Table ​ (Table3; 3 ; PICOT [ 14 ] and FINER [ 15 ]). The study domain is the theoretical source population from which the study population will be sampled, similar to the wording on a drug package insert that reads, “use this medication (study results) in people with this disease” [ 7 ].

The interpretation of study results as they apply to wider populations is known as generalization, and generalization can either be statistical or made using scientific inferences [ 16 ]. Generalization supported by statistical inferences is seen in studies on disease prevalence where the sample population is representative of the source population. By contrast, generalizations made using scientific inferences are not bound by the representativeness of the sample in the study; rather, the generalization should be plausible from the underlying scientific mechanisms as long as the study design is valid and nonbiased. Scientific inferences and generalizations are usually the aims of causal studies. 

Confounding: Confounding is a situation where true effects are obscured or confused [ 7 , 16 ]. Confounding variables or confounders affect the validity of a study’s outcomes and should be prevented or mitigated in the planning stages and further managed in the analytical stages. Confounders are also known as extraneous determinants in epidemiology due to their inherent and simultaneous relationships to both the determinant and outcome (Figure ​ (Figure2), 2 ), which are usually one-determinant-to-one outcome in causal clinical studies. The known confounders are also called observed confounders. These can be minimized using randomization, restriction, or a matching strategy. Residual confounding has occurred in a causal relationship when identified confounders were not measured accurately. Unobserved confounding occurs when the confounding effect is present as a variable or factor not observed or yet defined and, thus, not measured in the study. Age and gender are almost universal confounders followed by ethnicity and socio-economic status.

Confounders have three main characteristics. They are a potential risk factor for the disease, associated with the determinant of interest, and should not be an intermediate variable between the determinant and the outcome or a precursor to the determinant. For example, a sedentary lifestyle is a cause for acute coronary syndrome (ACS), and smoking could be a confounder but not cardiorespiratory unfitness (which is an intermediate factor between a sedentary lifestyle and ACS). For patients with ACS, not having a pair of sports shoes is not a confounder – it is a correlate for the sedentary lifestyle. Similarly, depression would be a precursor, not a confounder.

Sample size consideration: Sample size calculation provides the required number of participants to be recruited in a new study to detect true differences in the target population if they exist. Sample size calculation is based on three facets: an estimated difference in group sizes, the probability of α (Type I) and β (Type II) errors chosen based on the nature of the treatment or intervention, and the estimated variability (interval data) or proportion of the outcome (nominal data) [ 17 - 18 ]. The clinically important effect sizes are determined based on expert consensus or patients’ perception of benefit. Value and economic consideration have increasingly been included in sample size estimations. Sample size and the degree to which the sample represents the target population affect the accuracy and generalization of a study’s reported effects. 

Pilot study: Pilot studies assess the feasibility of the proposed research procedures on small sample size. Pilot studies test the efficiency of participant recruitment with minimal practice or service interruptions. Pilot studies should not be conducted to obtain a projected effect size for a larger study population because, in a typical pilot study, the sample size is small, leading to a large standard error of that effect size. This leads to bias when projected for a large population. In the case of underestimation, this could lead to inappropriately terminating the full-scale study. As the small pilot study is equally prone to bias of overestimation of the effect size, this would lead to an underpowered study and a failed full-scale study [ 19 ]. 

The Design of Data Collection

The “perfect” study design in the theoretical phase now faces the practical and realistic challenges of feasibility. This is the step where different methods for data collection are considered, with one selected as the most appropriate based on the theoretical design along with feasibility and efficiency. The goal of this stage is to achieve the highest possible validity with the lowest risk of biases given available resources and existing constraints. 

In causal research, data on the outcome and determinants are collected with utmost accuracy via a strict protocol to maximize validity and precision. The validity of an instrument is defined as the degree of fidelity of the instrument, measuring what it is intended to measure, that is, the results of the measurement correlate with the true state of an occurrence. Another widely used word for validity is accuracy. Internal validity refers to the degree of accuracy of a study’s results to its own study sample. Internal validity is influenced by the study designs, whereas the external validity refers to the applicability of a study’s result in other populations. External validity is also known as generalizability and expresses the validity of assuming the similarity and comparability between the study population and the other populations. Reliability of an instrument denotes the extent of agreeableness of the results of repeated measurements of an occurrence by that instrument at a different time, by different investigators or in a different setting. Other terms that are used for reliability include reproducibility and precision. Preventing confounders by identifying and including them in data collection will allow statistical adjustment in the later analyses. In descriptive research, outcomes must be confirmed with a referent standard, and the determinants should be as valid as those found in real clinical practice.

Common designs for data collection include cross-sectional, case-control, cohort, and randomized controlled trials (RCTs). Many other modern epidemiology study designs are based on these classical study designs such as nested case-control, case-crossover, case-control without control, and stepwise wedge clustered RCTs. A cross-sectional study is typically a snapshot of the study population, and an RCT is almost always a prospective study. Case-control and cohort studies can be retrospective or prospective in data collection. The nested case-control design differs from the traditional case-control design in that it is “nested” in a well-defined cohort from which information on the cohorts can be obtained. This design also satisfies the assumption that cases and controls represent random samples of the same study base. Table ​ Table4 4 provides examples of these data collection designs.

Additional aspects in data collection: No single design of data collection for any research question as stated in the theoretical design will be perfect in actual conduct. This is because of myriad issues facing the investigators such as the dynamic clinical practices, constraints of time and budget, the urgency for an answer to the research question, and the ethical integrity of the proposed experiment. Therefore, feasibility and efficiency without sacrificing validity and precision are important considerations in data collection design. Therefore, data collection design requires additional consideration in the following three aspects: experimental/non-experimental, sampling, and timing [ 7 ]:

Experimental or non-experimental: Non-experimental research (i.e., “observational”), in contrast to experimental, involves data collection of the study participants in their natural or real-world environments. Non-experimental researches are usually the diagnostic and prognostic studies with cross-sectional in data collection. The pinnacle of non-experimental research is the comparative effectiveness study, which is grouped with other non-experimental study designs such as cross-sectional, case-control, and cohort studies [ 20 ]. It is also known as the benchmarking-controlled trials because of the element of peer comparison (using comparable groups) in interpreting the outcome effects [ 20 ]. Experimental study designs are characterized by an intervention on a selected group of the study population in a controlled environment, and often in the presence of a similar group of the study population to act as a comparison group who receive no intervention (i.e., the control group). Thus, the widely known RCT is classified as an experimental design in data collection. An experimental study design without randomization is referred to as a quasi-experimental study. Experimental studies try to determine the efficacy of a new intervention on a specified population. Table ​ Table5 5 presents the advantages and disadvantages of experimental and non-experimental studies [ 21 ].

a May be an issue in cross-sectional studies that require a long recall to the past such as dietary patterns, antenatal events, and life experiences during childhood.

Once an intervention yields a proven effect in an experimental study, non-experimental and quasi-experimental studies can be used to determine the intervention’s effect in a wider population and within real-world settings and clinical practices. Pragmatic or comparative effectiveness are the usual designs used for data collection in these situations [ 22 ].

Sampling/census: Census is a data collection on the whole source population (i.e., the study population is the source population). This is possible when the defined population is restricted to a given geographical area. A cohort study uses the census method in data collection. An ecologic study is a cohort study that collects summary measures of the study population instead of individual patient data. However, many studies sample from the source population and infer the results of the study to the source population for feasibility and efficiency because adequate sampling provides similar results to the census of the whole population. Important aspects of sampling in research planning are sample size and representation of the population. Sample size calculation accounts for the number of participants needed to be in the study to discover the actual association between the determinant and outcome. Sample size calculation relies on the primary objective or outcome of interest and is informed by the estimated possible differences or effect size from previous similar studies. Therefore, the sample size is a scientific estimation for the design of the planned study.

A sampling of participants or cases in a study can represent the study population and the larger population of patients in that disease space, but only in prevalence, diagnostic, and prognostic studies. Etiologic and interventional studies do not share this same level of representation. A cross-sectional study design is common for determining disease prevalence in the population. Cross-sectional studies can also determine the referent ranges of variables in the population and measure change over time (e.g., repeated cross-sectional studies). Besides being cost- and time-efficient, cross-sectional studies have no loss to follow-up; recall bias; learning effect on the participant; or variability over time in equipment, measurement, and technician. A cross-sectional design for an etiologic study is possible when the determinants do not change with time (e.g., gender, ethnicity, genetic traits, and blood groups). 

In etiologic research, comparability between the exposed and the non-exposed groups is more important than sample representation. Comparability between these two groups will provide an accurate estimate of the effect of the exposure (risk factor) on the outcome (disease) and enable valid inference of the causal relation to the domain (the theoretical population). In a case-control study, a sampling of the control group should be taken from the same study population (study base), have similar profiles to the cases (matching) but do not have the outcome seen in the cases. Matching important factors minimizes the confounding of the factors and increases statistical efficiency by ensuring similar numbers of cases and controls in confounders’ strata [ 23 - 24 ]. Nonetheless, perfect matching is neither necessary nor achievable in a case-control study because a partial match could achieve most of the benefits of the perfect match regarding a more precise estimate of odds ratio than statistical control of confounding in unmatched designs [ 25 - 26 ]. Moreover, perfect or full matching can lead to an underestimation of the point estimates [ 27 - 28 ].

Time feature: The timing of data collection for the determinant and outcome characterizes the types of studies. A cross-sectional study has the axis of time zero (T = 0) for both the determinant and the outcome, which separates it from all other types of research that have time for the outcome T > 0. Retrospective or prospective studies refer to the direction of data collection. In retrospective studies, information on the determinant and outcome have been collected or recorded before. In prospective studies, this information will be collected in the future. These terms should not be used to describe the relationship between the determinant and the outcome in etiologic studies. Time of exposure to the determinant, the time of induction, and the time at risk for the outcome are important aspects to understand. Time at risk is the period of time exposed to the determinant risk factors. Time of induction is the time from the sufficient exposure to the risk or causal factors to the occurrence of a disease. The latent period is when the occurrence of a disease without manifestation of the disease such as in “silence” diseases for example cancers, hypertension and type 2 diabetes mellitus which is detected from screening practices. Figure ​ Figure3 3 illustrates the time features of a variable. Variable timing is important for accurate data capture. 

The Design of Statistical Analysis

Statistical analysis of epidemiologic data provides the estimate of effects after correcting for biases (e.g., confounding factors) measures the variability in the data from random errors or chance [ 7 , 16 , 29 ]. An effect estimate gives the size of an association between the studied variables or the level of effectiveness of an intervention. This quantitative result allows for comparison and assessment of the usefulness and significance of the association or the intervention between studies. This significance must be interpreted with a statistical model and an appropriate study design. Random errors could arise in the study resulting from unexplained personal choices by the participants. Random error is, therefore, when values or units of measurement between variables change in non-concerted or non-directional manner. Conversely, when these values or units of measurement between variables change in a concerted or directional manner, we note a significant relationship as shown by statistical significance. 

Variability: Researchers almost always collect the needed data through a sampling of subjects/participants from a population instead of a census. The process of sampling or multiple sampling in different geographical regions or over different periods contributes to varied information due to the random inclusion of different participants and chance occurrence. This sampling variation becomes the focus of statistics when communicating the degree and intensity of variation in the sampled data and the level of inference in the population. Sampling variation can be influenced profoundly by the total number of participants and the width of differences of the measured variable (standard deviation). Hence, the characteristics of the participants, measurements and sample size are all important factors in planning a study.

Statistical strategy: Statistical strategy is usually determined based on the theoretical and data collection designs. Use of a prespecified statistical strategy (including the decision to dichotomize any continuous data at certain cut-points, sub-group analysis or sensitive analyses) is recommended in the study proposal (i.e., protocol) to prevent data dredging and data-driven reports that predispose to bias. The nature of the study hypothesis also dictates whether directional (one-tailed) or non-directional (two-tailed) significance tests are conducted. In most studies, two-sided tests are used except in specific instances when unidirectional hypotheses may be appropriate (e.g., in superiority or non-inferiority trials). While data exploration is discouraged, epidemiological research is, by nature of its objectives, statistical research. Hence, it is acceptable to report the presence of persistent associations between any variables with plausible underlying mechanisms during the exploration of the data. The statistical methods used to produce the results should be explicitly explained. Many different statistical tests are used to handle various kinds of data appropriately (e.g., interval vs discrete), and/or the various distribution of the data (e.g., normally distributed or skewed). For additional details on statistical explanations and underlying concepts of statistical tests, readers are recommended the references as cited in this sentence [ 30 - 31 ]. 

Steps in statistical analyses: Statistical analysis begins with checking for data entry errors. Duplicates are eliminated, and proper units should be confirmed. Extremely low, high or suspicious values are confirmed from the source data again. If this is not possible, this is better classified as a missing value. However, if the unverified suspicious data are not obviously wrong, they should be further examined as an outlier in the analysis. The data checking and cleaning enables the analyst to establish a connection with the raw data and to anticipate possible results from further analyses. This initial step involves descriptive statistics that analyze central tendency (i.e., mode, median, and mean) and dispersion (i.e., (minimum, maximum, range, quartiles, absolute deviation, variance, and standard deviation) of the data. Certain graphical plotting such as scatter plot, a box-whiskers plot, histogram or normal Q-Q plot are helpful at this stage to verify data normality in distribution. See Figure ​ Figure4 4 for the statistical tests available for analyses of different types of data.

Once data characteristics are ascertained, further statistical tests are selected. The analytical strategy sometimes involves the transformation of the data distribution for the selected tests (e.g., log, natural log, exponential, quadratic) or for checking the robustness of the association between the determinants and their outcomes. This step is also referred to as inferential statistics whereby the results are about hypothesis testing and generalization to the wider population that the study’s sampled participants represent. The last statistical step is checking whether the statistical analyses fulfill the assumptions of that particular statistical test and model to avoid violation and misleading results. These assumptions include evaluating normality, variance homogeneity, and residuals included in the final statistical model. Other statistical values such as Akaike information criterion, variance inflation factor/tolerance, and R2 are also considered when choosing the best-fitted models. Transforming raw data could be done, or a higher level of statistical analyses can be used (e.g., generalized linear models and mixed-effect modeling). Successful statistical analysis allows conclusions of the study to fit the data. 

Bayesian and Frequentist statistical frameworks: Most of the current clinical research reporting is based on the frequentist approach and hypotheses testing p values and confidence intervals. The frequentist approach assumes the acquired data are random, attained by random sampling, through randomized experiments or influences, and with random errors. The distribution of the data (its point estimate and confident interval) infers a true parameter in the real population. The major conceptual difference between Bayesian statistics and frequentist statistics is that in Bayesian statistics, the parameter (i.e., the studied variable in the population) is random and the data acquired is real (true or fix). Therefore, the Bayesian approach provides a probability interval for the parameter. The studied parameter is random because it could vary and be affected by prior beliefs, experience or evidence of plausibility. In the Bayesian statistical approach, this prior belief or available knowledge is quantified into a probability distribution and incorporated into the acquired data to get the results (i.e., the posterior distribution). This uses mathematical theory of Bayes’ Theorem to “turn around” conditional probabilities.

The goal of research reporting is to present findings succinctly and timely via conference proceedings or journal publication. Concise and explicit language use, with all the necessary details to enable replication and judgment of the study applicability, are the guiding principles in clinical studies reporting.

Writing for Reporting

Medical writing is very much a technical chore that accommodates little artistic expression. Research reporting in medicine and health sciences emphasize clear and standardized reporting, eschewing adjectives and adverbs extensively used in popular literature. Regularly reviewing published journal articles can familiarize authors with proper reporting styles and help enhance writing skills. Authors should familiarize themselves with standard, concise, and appropriate rhetoric for the intended audience, which includes consideration for journal reviewers, editors, and referees. However, proper language can be somewhat subjective. While each publication may have varying requirements for submission, the technical requirements for formatting an article are usually available via author or submission guidelines provided by the target journal. 

Research reports for publication often contain a title, abstract, introduction, methods, results, discussion, and conclusions section, and authors may want to write each section in sequence. However, best practices indicate the abstract and title should be written last. Authors may find that when writing one section of the report, ideas come to mind that pertains to other sections, so careful note taking is encouraged. One effective approach is to organize and write the result section first, followed by the discussion and conclusions sections. Once these are drafted, write the introduction, abstract, and the title of the report. Regardless of the sequence of writing, the author should begin with a clear and relevant research question to guide the statistical analyses, result interpretation, and discussion. The study findings can be a motivator to propel the author through the writing process, and the conclusions can help the author draft a focused introduction.

Writing for Publication

Specific recommendations on effective medical writing and table generation are available [ 32 ]. One such resource is Effective Medical Writing: The Write Way to Get Published, which is an updated collection of medical writing articles previously published in the Singapore Medical Journal [ 33 ]. The British Medical Journal’s Statistics Notes series also elucidates common and important statistical concepts and usages in clinical studies. Writing guides are also available from individual professional societies, journals, or publishers such as Chest (American College of Physicians) medical writing tips, PLoS Reporting guidelines collection, Springer’s Journal Author Academy, and SAGE’s Research methods [ 34 - 37 ]. Standardized research reporting guidelines often come in the form of checklists and flow diagrams. Table ​ Table6 6 presents a list of reporting guidelines. A full compilation of these guidelines is available at the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network website [ 38 ] which aims to improve the reliability and value of medical literature by promoting transparent and accurate reporting of research studies. Publication of the trial protocol in a publicly available database is almost compulsory for publication of the full report in many potential journals.

Graphics and Tables

Graphics and tables should emphasize salient features of the underlying data and should coherently summarize large quantities of information. Although graphics provide a break from dense prose, authors must not forget that these illustrations should be scientifically informative, not decorative. The titles for graphics and tables should be clear, informative, provide the sample size, and use minimal font weight and formatting only to distinguish headings, data entry or to highlight certain results. Provide a consistent number of decimal points for the numerical results, and with no more than four for the P value. Most journals prefer cell-delineated tables created using the table function in word processing or spreadsheet programs. Some journals require specific table formatting such as the absence or presence of intermediate horizontal lines between cells.

Decisions of authorship are both sensitive and important and should be made at an early stage by the study’s stakeholders. Guidelines and journals’ instructions to authors abound with authorship qualifications. The guideline on authorship by the International Committee of Medical Journal Editors is widely known and provides a standard used by many medical and clinical journals [ 39 ]. Generally, authors are those who have made major contributions to the design, conduct, and analysis of the study, and who provided critical readings of the manuscript (if not involved directly in manuscript writing). 

Picking a target journal for submission

Once a report has been written and revised, the authors should select a relevant target journal for submission. Authors should avoid predatory journals—publications that do not aim to advance science and disseminate quality research. These journals focus on commercial gain in medical and clinical publishing. Two good resources for authors during journal selection are Think-Check-Submit and the defunct Beall's List of Predatory Publishers and Journals (now archived and maintained by an anonymous third-party) [ 40 , 41 ]. Alternatively, reputable journal indexes such as Thomson Reuters Journal Citation Reports, SCOPUS, MedLine, PubMed, EMBASE, EBSCO Publishing's Electronic Databases are available areas to start the search for an appropriate target journal. Authors should review the journals’ names, aims/scope, and recently published articles to determine the kind of research each journal accepts for publication. Open-access journals almost always charge article publication fees, while subscription-based journals tend to publish without author fees and instead rely on subscription or access fees for the full text of published articles.

Conclusions

Conducting a valid clinical research requires consideration of theoretical study design, data collection design, and statistical analysis design. Proper study design implementation and quality control during data collection ensures high-quality data analysis and can mitigate bias and confounders during statistical analysis and data interpretation. Clear, effective study reporting facilitates dissemination, appreciation, and adoption, and allows the researchers to affect real-world change in clinical practices and care models. Neutral or absence of findings in a clinical study are as important as positive or negative findings. Valid studies, even when they report an absence of expected results, still inform scientific communities of the nature of a certain treatment or intervention, and this contributes to future research, systematic reviews, and meta-analyses. Reporting a study adequately and comprehensively is important for accuracy, transparency, and reproducibility of the scientific work as well as informing readers.

Acknowledgments

The author would like to thank Universiti Putra Malaysia and the Ministry of Higher Education, Malaysia for their support in sponsoring the Ph.D. study and living allowances for Boon-How Chew.

The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.

The materials presented in this paper is being organized by the author into a book.

A randomized double-blind placebo-controlled clinical trial of Guanfacine Extended Release for aggression and self-injurious behavior associated with Prader-Willi Syndrome

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Introduction: Prader-Willi Syndrome (PWS), a rare genetic disorder, affects development and behavior, frequently resulting in self-injury, aggression, hyperphagia, oppositional behavior, impulsivity and over-activity causing significant morbidity. Currently, limited therapeutic options are available to manage these neuropsychiatric manifestations. The aim of this clinical trial was to assess the efficacy of guanfacine-extended release (GXR) in reducing aggression and self-injury in individuals with PWS. Trial Design: Randomized, double-blind, placebo-controlled trial conducted under IRB approval. Methods: Subjects with a diagnosis of PWS, 6-35 years of age, with moderate to severe aggressive and/or self-injurious behavior as determined by the Clinical Global Impression (CGI)-Severity scale, were included in an 8-week double-blind, placebo-controlled, fixed-flexible dose clinical trial of GXR, that was followed by an 8-week open-label extension phase. Validated behavioral instruments and physician assessments measured the efficacy of GXR treatment, its safety and tolerability. Results: GXR was effective in reducing aggression/agitation and hyperactivity/noncompliance as measured by the Aberrant Behavior Checklist (ABC) scales (p=0.03). Overall aberrant behavior scores significantly reduced in the GXR arm. Aggression as measured by the Modified Overt Aggression Scale (MOAS) also showed a significant reduction. Skin-picking lesions as measured by the Self Injury Trauma (SIT) scale decreased in response to GXR. No serious adverse events were experienced by any of the study participants. Fatigue /sedation was the only adverse event significantly associated with GXR. The GXR group demonstrated significant overall clinical improvement as measured by the CGI-Improvement (CGI-I) scale. (p<0.01). Conclusion: Findings of this pragmatic trial strongly support the use of GXR for treatment of aggression, skin picking, and hyperactivity in children, adolescents, and adults with PWS. Trial Registration: ClinicalTrials.gov Identifier - NCT05657860

Competing Interest Statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: DS has served as a consultant to Soleno Therapeutics, Acadia Pharmaceuticals, Tonix Pharmaceuticals, and Consynance Therapeutics. MS and TJ have no other competing interests to report.

Clinical Trial

ClinicalTrials.gov identifier: NCT05657860

Funding Statement

Author declarations.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was approved by the Institutional Review Board of Maimonides Medical Center (# 2020-11-03-MMC). Written, IRB-approved informed consent was obtained from each participant's parent or legal guardian, and assent was obtained from each participant, as applicable.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Data Availability

All relevant data are within the manuscript and its Supporting Information files and will be available upon its publication.

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