Clinical study design

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Clinical study design is the formulation of trials and experiments, as well as observational studies in medical, clinical and other types of research (e.g., epidemiological) involving human beings. [1] The goal of a clinical study is to assess the safety, efficacy, and / or the mechanism of action of an investigational medicinal product (IMP) [2] or procedure, or new drug or device that is in development, but potentially not yet approved by a health authority (e.g. Food and Drug Administration). [3] It can also be to investigate a drug, device or procedure that has already been approved but is still in need of further investigation, typically with respect to long-term effects or cost-effectiveness. [4]

Contents

Some of the considerations here are shared under the more general topic of design of experiments but there can be others, in particular related to patient confidentiality and ethics.

Outline of types of designs for clinical studies

Treatment studies

Observational studies

1. Descriptive

2. Analytical

Important considerations

When choosing a study design, many factors must be taken into account. Different types of studies are subject to different types of bias. For example, recall bias is likely to occur in cross-sectional or case-control studies where subjects are asked to recall exposure to risk factors. Subjects with the relevant condition (e.g. breast cancer) may be more likely to recall the relevant exposures that they had undergone (e.g. hormone replacement therapy) than subjects who don't have the condition.[ citation needed ]

The ecological fallacy may occur when conclusions about individuals are drawn from analyses conducted on grouped data. The nature of this type of analysis tends to overestimate the degree of association between variables.[ citation needed ]

Seasonal studies

Conducting studies in seasonal indications (such as allergies, Seasonal Affective Disorder, influenza, and others) can complicate a trial as patients must be enrolled quickly. Additionally, seasonal variations and weather patterns can affect a seasonal study. [15] [16]

Other terms

See also

Related Research Articles

<span class="mw-page-title-main">Randomized controlled trial</span> Form of scientific experiment

A randomized controlled trial is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical techniques, medical devices, diagnostic procedures or other medical treatments.

<span class="mw-page-title-main">Clinical trial</span> Phase of clinical research in medicine

Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted.

In a blind or blinded experiment, information which may influence the participants of the experiment is withheld until after the experiment is complete. Good blinding can reduce or eliminate experimental biases that arise from a participants' expectations, observer's effect on the participants, observer bias, confirmation bias, and other sources. A blind can be imposed on any participant of an experiment, including subjects, researchers, technicians, data analysts, and evaluators. In some cases, while blinding would be useful, it is impossible or unethical. For example, it is not possible to blind a patient to their treatment in a physical therapy intervention. A good clinical protocol ensures that blinding is as effective as possible within ethical and practical constraints.

A cohort study is a particular form of longitudinal study that samples a cohort, performing a cross-section at intervals through time. It is a type of panel study where the individuals in the panel share a common characteristic.

A case–control study is a type of observational study in which two existing groups differing in outcome are identified and compared on the basis of some supposed causal attribute. Case–control studies are often used to identify factors that may contribute to a medical condition by comparing subjects who have the condition with patients who do not have the condition but are otherwise similar. They require fewer resources but provide less evidence for causal inference than a randomized controlled trial. A case–control study is often used to produce an odds ratio. Some statistical methods make it possible to use a case–control study to also estimate relative risk, risk differences, and other quantities.

<span class="mw-page-title-main">Scientific control</span> Methods employed to reduce error in science tests

A scientific control is an experiment or observation designed to minimize the effects of variables other than the independent variable. This increases the reliability of the results, often through a comparison between control measurements and the other measurements. Scientific controls are a part of the scientific method.

In the design of experiments, hypotheses are applied to experimental units in a treatment group. In comparative experiments, members of a control group receive a standard treatment, a placebo, or no treatment at all. There may be more than one treatment group, more than one control group, or both.

Clinical endpoints or clinical outcomes are outcome measures referring to occurrence of disease, symptom, sign or laboratory abnormality constituting a target outcome in clinical research trials. The term may also refer to any disease or sign that strongly motivates withdrawal of an individual or entity from the trial, then often termed a humane (clinical) endpoint.

Overdiagnosis is the diagnosis of disease that will never cause symptoms or death during a patient's ordinarily expected lifetime and thus presents no practical threat regardless of being pathologic. Overdiagnosis is a side effect of screening for early forms of disease. Although screening saves lives in some cases, in others it may turn people into patients unnecessarily and may lead to treatments that do no good and perhaps do harm. Given the tremendous variability that is normal in biology, it is inherent that the more one screens, the more incidental findings will generally be found. For a large percentage of them, the most appropriate medical response is to recognize them as something that does not require intervention; but determining which action a particular finding warrants can be very difficult, whether because the differential diagnosis is uncertain or because the risk ratio is uncertain.

A hierarchy of evidence, comprising levels of evidence (LOEs), that is, evidence levels (ELs), is a heuristic used to rank the relative strength of results obtained from experimental research, especially medical research. There is broad agreement on the relative strength of large-scale, epidemiological studies. More than 80 different hierarchies have been proposed for assessing medical evidence. The design of the study and the endpoints measured affect the strength of the evidence. In clinical research, the best evidence for treatment efficacy is mainly from meta-analyses of randomized controlled trials (RCTs). Systematic reviews of completed, high-quality randomized controlled trials – such as those published by the Cochrane Collaboration – rank the same as systematic review of completed high-quality observational studies in regard to the study of side effects. Evidence hierarchies are often applied in evidence-based practices and are integral to evidence-based medicine (EBM).

<span class="mw-page-title-main">Observational study</span> Study with uncontrolled variable of interest

In fields such as epidemiology, social sciences, psychology and statistics, an observational study draws inferences from a sample to a population where the independent variable is not under the control of the researcher because of ethical concerns or logistical constraints. One common observational study is about the possible effect of a treatment on subjects, where the assignment of subjects into a treated group versus a control group is outside the control of the investigator. This is in contrast with experiments, such as randomized controlled trials, where each subject is randomly assigned to a treated group or a control group. Observational studies, for lacking an assignment mechanism, naturally present difficulties for inferential analysis.

A case series is a type of medical research study that tracks subjects with a known exposure, such as patients who have received a similar treatment, or examines their medical records for exposure and outcome. Case series may be consecutive or non-consecutive, depending on whether all cases presenting to the reporting authors over a period were included, or only a selection. When information on more than three patients is included, the case series is considered to be a systematic investigation designed to contribute to generalizable knowledge, and therefore submission is required to an institutional review board (IRB). Case series usually contain demographic information about the patient(s), for example, age, gender, ethnic origin. etc.

<span class="mw-page-title-main">Quasi-experiment</span> Empirical interventional study

A quasi-experiment is an empirical interventional study used to estimate the causal impact of an intervention on target population without random assignment. Quasi-experimental research shares similarities with the traditional experimental design or randomized controlled trial, but it specifically lacks the element of random assignment to treatment or control. Instead, quasi-experimental designs typically allow the researcher to control the assignment to the treatment condition, but using some criterion other than random assignment.

<span class="mw-page-title-main">Retrospective cohort study</span> Historic cohort study

A retrospective cohort study, also called a historic cohort study, is a longitudinal cohort study used in medical and psychological research. A cohort of individuals that share a common exposure factor is compared with another group of equivalent individuals not exposed to that factor, to determine the factor's influence on the incidence of a condition such as disease or death. Retrospective cohort studies have existed for approximately as long as prospective cohort studies.

<span class="mw-page-title-main">Prospective cohort study</span> Longitudinal cohort study

A prospective cohort study is a longitudinal cohort study that follows over time a group of similar individuals (cohorts) who differ with respect to certain factors under study, to determine how these factors affect rates of a certain outcome. For example, one might follow a cohort of middle-aged truck drivers who vary in terms of smoking habits, to test the hypothesis that the 20-year incidence rate of lung cancer will be highest among heavy smokers, followed by moderate smokers, and then nonsmokers.

A glossary of terms used in clinical research.

The following outline is provided as an overview of and topical guide to clinical research:

<span class="mw-page-title-main">Placebo-controlled study</span>

Placebo-controlled studies are a way of testing a medical therapy in which, in addition to a group of subjects that receives the treatment to be evaluated, a separate control group receives a sham "placebo" treatment which is specifically designed to have no real effect. Placebos are most commonly used in blinded trials, where subjects do not know whether they are receiving real or placebo treatment. Often, there is also a further "natural history" group that does not receive any treatment at all.

<span class="mw-page-title-main">Phases of clinical research</span> Clinical trial stages using human subjects

The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for drug safety in a few human subjects, then expand to many study participants to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays.

References

  1. ↑ Miquel Porta (2014) "A dictionary of epidemiology", 6th edn, New York: Oxford University Press. ISBN   9780199976737.
  2. ↑ "Investigational Medicinal Product (IMP) | Noclor". www.noclor.nhs.uk. Archived from the original on 2020-09-26. Retrieved 2019-11-19.
  3. ↑ Ann (April 14, 2006). "Clinical Study Management". ProMedica International. Retrieved June 4, 2019.
  4. ↑ Nichols, Hannah (May 18, 2018). "How do clinical trials work and who can participate?". Medical News Today. Retrieved June 4, 2019.
  5. ↑ Shiel, William C. Jr. (December 21, 2018). "Randomized control trial". Medicine Net. Retrieved June 4, 2019.
  6. ↑ "Are these data real? Statistical methods for the detection of data fabrication in clinical trials". The BMJ. July 28, 2005. Retrieved June 4, 2019.
  7. ↑ Shiel, William C. Jr. (December 21, 2018). "Nonblinded study". Medicine Net. Retrieved June 4, 2019.
  8. ↑ Mahajan, Rajiv; Gupta, Kapil (August 2012). "Adaptive design clinical trials: Methodology, challenges and prospect". Indian Journal of Pharmacology. 42 (4): 201–7. doi: 10.4103/0253-7613.68417 . PMC   2941608 . PMID   20927243.
  9. ↑ "NCI Dictionary of Cancer Terms". National Cancer Institute. 2 February 2011. Retrieved June 4, 2019.
  10. ↑ Kontopantelis, E.; Doran, T.; Springate, D. A.; Buchan, I.; Reeves, D. (June 9, 2015). "Regression based quasi-experimental approach when randomisation is not an option: interrupted time series analysis". The BMJ. 350: h2750. doi:10.1136/bmj.h2750. PMC   4460815 . PMID   26058820.
  11. 1 2 Mathes, Tim; Pieper, Dawid (July 17, 2017). "Clarifying the distinction between case series and cohort studies in systematic reviews of comparative studies: potential impact on body of evidence and workload". BMC Med Res Methodol. 17 (1): 107. doi: 10.1186/s12874-017-0391-8 . PMC   5513097 . PMID   28716005.
  12. ↑ "NCI Dictionary of Cancer Terms". National Cancer Institute. 2 February 2011. Retrieved June 4, 2019.
  13. ↑ "NCI Dictionary of Cancer Terms". National Cancer Institute. 2 February 2011. Retrieved June 4, 2019.
  14. ↑ "NCI Dictionary of Cancer Terms". National Cancer Institute. 2 February 2011. Retrieved June 4, 2019.
  15. ↑ Yamin Khan; Sarah Tilly. "Flu, Season, Diseases Affect Trials". Applied Clinical Trials Online. Archived from the original on 11 July 2011. Retrieved 26 February 2010.
  16. ↑ Yamin Khan; Sarah Tilly. "Seasonality: The Clinical Trial Manager's Logistical Challenge" (PDF). published by: Pharm-Olam International (POI). Archived from the original (PDF) on 15 July 2011. Retrieved 26 April 2010.
  17. ↑ "Prospective vs. Retrospective Studies". Stats Direct. Retrieved May 30, 2019.
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