Innovative Clinical Trial Methods: Key Approaches and Techniques

What is Clinical Trial Method?

Introduction

Clinical trial methods integrate strategies to achieve valid conclusions about trial objectives and safeguard participants, utilizing both quantitative and qualitative research approaches. Emphasising the significance of statistical reasoning in clinical research, a clinical trial method is integral to the methodology of clinical trials. Therefore, understanding the various types of clinical trial methods is crucial for conducting effective clinical research. Clinical trials are essential in comparing the impacts of one intervention against another, involving participants who may be patients, healthy individuals, or a combination of both. They play a crucial role in advancing our understanding of human health and disease, as well as in the development of innovative and effective therapies. This article delves into a comprehensive exploration of clinical trial methods highlighting their importance in clinical trials.

Importance and Considerations in Methodology

Conducting clinical research necessitates a systematic approach, involving meticulous planning, execution, and sampling to ensure the acquisition of reliable and validated results. Researchers must possess a comprehensive understanding of various research methodologies. The choice of a specific methodology is contingent upon factors such as:

Hypothesis under investigation
Research question or problem statement
Study objectives
Study’s nature
Participant pool
Controls
Intervention
Variables

The credibility and validity of results hinge on a well-defined overall study design, encompassing clear objectives, reproducible methodology, careful data collection and analysis to minimise errors and bias, and effective reporting of findings. Therefore, the selection of an appropriate methodology is crucial for obtaining valid results, emphasising the necessity for researchers to have a solid grasp of research methodology.

Types of Clinical Research

Clinical research can be broadly classified as quantitative or qualitative based on study design. Further categorisation of quantitative into descriptive or analytical considers data collection techniques and the direction of causality, including factors like time relationships.

Types of Clinical Research

Fig. 1: Types of Clinical Research

Quantitative Clinical Research

Quantitative Clinical Research involves the systematic collection and analysis of numerical data to quantify relationships, patterns, and trends within a larger population.

Descriptive Research

Descriptive research involves recording and reporting new or unusual events, like disease prevalence in a family, without randomisation. It includes case reports for individual patients, case series for common characteristics, and surveillance studies for continuous monitoring of disease occurrence in a population.

Analytical Research

Analytical studies, unlike descriptive studies, incorporate control groups for comparative evaluations. These can be experimental (intervention) studies or observational (non-intervention) studies.

Observational Studies

Non-interventional studies where patients receive therapy based on diagnosis and therapeutic need. They include therapeutic, prognostic, and observational drug studies, case series, and single case reports.

Fig. 2: Classification of Observational Studies

Observational studies can be broadly classified as individual and aggregate studies:

Aggregate Observation Studies

These studies aggregate individual-level data based on geographic area, year, or other parameters. They provide insights into the distribution of diseases in populations, such as aggregating data on COVID-19 or cancer registries.

Individual Observation Studies

These studies analyse disaggregated individual results, grouping subjects based on outcomes or exposures. These are further divided into the following:

Case-control studies group subjects based on selected outcomes, comparing exposure experiences between case and control groups.
Cohort studies group subjects based on exposure, allowing the study of multiple outcomes.
- Retrospective cohort studies look back at archived data, while prospective cohort studies follow cohorts over time.
Cross-sectional studies assess exposures and outcomes concurrently, providing prevalence data but not causation insights.

Experimental Studies

Experimental studies encompass intervention trials, comprising preclinical trials conducted on animals and clinical trials conducted on humans. They employ main designs such as randomised controlled trials and non-randomised controlled trials.

Fig. 3: Classification of Experimental Studies

Non-randomised Studies

In these studies, the study population is chosen based on predetermined criteria, and intervention is prescribed according to the course of the disease. In cases where randomisation is not feasible or ethical, such as surgical interventions for specific patient groups, non-randomised designs are employed. Non-randomised studies can be categorised into three additional types:

Quasi-experiment: This involves assigning exposure to the intervention similar to a randomised controlled trial, but subjects are not randomised.
Field Trial: These large-scale studies assess therapeutic interventions, such as the efficacy of COVID-19 vaccines. They require numerous samples, especially when the incidence of a particular disease is low.
Community Trial: Interventions are allocated to a community group, as seen in testing the effects of water fluoridation on communities.

Randomised Controlled Trials

These trials typically involve random division of study participants into two groups, with the experimental group receiving the intervention and the control group not receiving it (or possibly receiving an existing standard of care). The assignment of the intervention is generally randomised. Subsequently, participants are monitored over a period to evaluate changes in outcomes within both groups. The comparison of outcomes in these groups enables an assessment of the intervention’s impact. As these studies are conducted with a prospective approach, wherein the investigator allocates the intervention, this study type offers a robust level of evidence and is frequently regarded as the gold standard. Randomised controlled trials can be categorised into four additional types:

Parallel Group Design: This is the most common method. In this design, a substantial number of subjects or patients are enrolled in two groups (experimental vs control), followed up, and observed for outcomes concurrently over a designated period.
Crossover Design: This design involves the sequential administration of two interventions in the two enrolled groups (experimental vs control), and the assessment of their effects. It applies to drugs with reversible and transient effects. Notably, the number of required patients is smaller compared to other designs.
Factorial Design: This study design lets investigators see how one or more interventions; both together affect the group of participants or patients. There are generally 4 groups in this design. One group receives both interventions, the other two groups receive one intervention each, and the last group is the control group.
Withdrawal Group Design: In this design type, interventions for chronic diseases are either halted or the dosage is reduced. This approach proves valuable for evaluating the optimal intervention duration for chronic conditions and assessing interventions for which conclusive evidence in the literature is lacking.

Quantitative Clinical Research

On the other hand, qualitative Clinical Research focuses on exploring and understanding the complexity of human experiences, behaviors, and perspectives through in-depth, non-numerical data collection and analysis.

Conclusion

Clinical research involves diverse methodologies, with descriptive studies capturing new events, while analytical studies employ control groups for comparative evaluations. Observational studies, categorised as aggregate and individual, provide valuable insights. Experimental studies, including randomised controlled trials and non-randomised studies, play a crucial role in intervention research. Non-randomised studies, like quasi-experiments and community trials, offer flexibility in design. While, randomised controlled trials with investigator-allocated interventions are highly regarded for providing robust evidence, often considered the gold standard.

Types of Clinical Research
Quantitative					Qualitative
Descriptive	Analytical
Case report Case Series Surveillance studies	Observational Studies		Experimental Studies
	Individual	Aggregate	Non-Randomised Studies	Randomised Controlled Trials
	Case-control Studies Cohort Studies Cross-sectional Studies	Quasi Field Trial Community Trial	Parallel Group Design Crossover Design Factorial Design Withdrawal Group Design

Table 1: Exploring the landscape of clinical trials: From diverse observational studies to the gold standard of prospectively conducted experimental trials

References

Chen, Ding-Geng & Peace, Karl. (2010). Clinical Trial Methodology. [Internet]. [cited 2023 Dec 18]. Available from: https://www.researchgate.net/publication/267764342_Clinical_Trial_Methodology
Kiani AK, Naureen Z, Pheby D, et al. Methodology for clinical research. J Prev Med Hyg. 2022;63(2 Suppl 3):E267-E278. Published 2022 Oct 17. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710407/
Clinical trials. NHS. [Internet]. [cited 2023 Dec 17]. Available from: https://www.nhs.uk/conditions/clinical-trials/
Lesson 1: Clinical Trials Overview. [Internet]. [cited 2023 Dec 18]. Available from: https://ccrod.cancer.gov/confluence/download/attachments/164235639/EUPATI%20Core%20Educational%20Materials%20for%20REiNS%20%28002%29.pdf?version=1&modificationDate=1539610009020&api=v2
Setia MS. Methodology Series Module 4: Clinical Trials. Indian J Dermatol. 2016;61(4):393-402. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966397/

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