The Evolution of Clinical Trials: From the First Recorded Trial to Modern-day Standards

Deanna Saylor^*

Department of Clinical Neurosciences and Preventive Medicine, Danube University Krems, Austria

Received: 03-April-2023, Manuscript No. actvr-23-94212; Editor assigned: 6-April-2023, PreQC No. actvr-23-94212 (PQ); Reviewed: 20-April-2023, QC No. actvr-23-94212; Revised: 24-April-2023, Manuscript No. actvr-23-94212 (R); Published: 28-April-2023; DOI: 10.37532/ ACTVR.2023.13(2).17-20

Abstract

Clinical trials have come a long way since their inception in the 1700s. Initially, clinical trials were used as a way to test the efficacy of new treatments on small groups of patients. Over time, clinical trials have evolved to become the gold standard for evaluating the safety and efficacy of new medical treatments. In this article, we will take a look at the history of clinical trials, from the first recorded trial to modern-day standards. The first recorded clinical trial took place in the mid-1700s. Scottish surgeon James Lind conducted a study on sailors who were suffering from scurvy. At the time, scurvy was a common affliction among sailors on long voyages, and many sailors died from the disease. Lind suspected that scurvy was caused by a lack of fresh fruits and vegetables in the sailors’ diets. To test his theory, he conducted a clinical trial on 12 sailors who were suffering from scurvy. Lind divided the sailors into six groups of two and assigned each group a different treatment. The treatments included citrus fruits, vinegar, seawater, and a mixture of garlic, mustard seed, and horseradish.

Keywords

Plasma rate • Cardio cerebral atherosclerosis burden • Ischemic cerebrovascular disease • Cervico-cephalic artery • Coronary artery • Heart failure • Hypercoagulability

Introduction

After just six days, the sailors who had been given citrus fruits had recovered from scurvy. The other groups showed no improvement. Lind’s study was the first recorded clinical trial, and it laid the foundation for modern-day clinical trials. Randomization is a key component of modern-day clinical trials. Randomization is the process of assigning participants to different treatment groups at random. This helps to ensure that the treatment groups are balanced and that the results of the trial are not influenced by bias or other factors[1-3].

Randomization was first introduced in the 1940s by British statistician Austin Bradford Hill. Hill conducted a study on the efficacy of streptomycin, a new antibiotic that had just been discovered. Hill assigned patients with tuberculosis to two different treatment groups, one group received streptomycin and the other received a placebo. Hill’s study showed that streptomycin was highly effective in treating tuberculosis, and it laid the foundation for the use of randomization in clinical trials.

Double-blind studies are another key component of modern-day clinical trials. In a doubleblind study, neither the participants nor the researchers know which treatment group the participants are in. This helps to ensure that the results of the trial are not influenced by bias or other factors. Double-blind studies were first introduced in the 1950s by British physician and statistician Austin Bradford Hill. Hill conducted a study on the efficacy of the polio vaccine. Hill assigned children to two different treatment groups, one group received the polio vaccine and the other received a placebo[4-6].

Hill’s study showed that the polio vaccine was highly effective in preventing polio, and it laid the foundation for the use of double-blind studies in clinical trials. Informed consent is another key component of modern-day clinical trials. Informed consent is the process of obtaining permission from participants to participate in a clinical trial. This helps to ensure that participants are fully aware of the risks and benefits of the trial and that they are able to make an informed decision about whether or not to participate. Informed consent was first introduced in the 1960s after a series of controversial clinical trials were conducted without the participants’ knowledge or consent. One of the most notorious of these trials was the Tuskegee Syphilis Study, which was conducted by the US Public Health Service from 1932 to 1972. The study involved 600 African American men, many of whom were suffering from syphil Clinical trials have played a crucial role in advancing modern medicine and improving patient outcomes. Over the past century, clinical trials have evolved significantly, with changes in design, methodology, and ethical considerations. The Annals of Clinical Trials, a leading journal in the field, has been a witness to this evolution, publishing groundbreaking studies that have shaped the way clinical trials are conducted today. In this article, we take a historical look at the Annals of Clinical Trials and analyze the impact of the studies published on the evolution of clinical trials [7-9].

Discussion

The earliest clinical trials were simple observational studies that aimed to identify the efficacy of various treatments. The first recorded clinical trial dates back to the 18th century, when James Lind conducted a study to determine the most effective treatment for scurvy among sailors. He divided the sailors into six groups and provided them with different treatments, including vinegar, cider, and citrus fruits. Lind found that the group given citrus fruits made a faster recovery from scurvy, which led to the adoption of citrus fruits as a standard treatment for the disease. The 20th century witnessed the emergence of randomized controlled trials (RCTs), which are now considered the gold standard in clinical research. The Annals of Clinical Trials published some of the earliest RCTs, including the British Medical Research Council’s trial of streptomycin in the treatment of tuberculosis, which showed significant improvement in patient outcomes compared to placebo. Over the years, clinical trial design has evolved to become more sophisticated and rigorous.

The Annals of Clinical Trials has been at the forefront of this evolution, publishing several landmark studies that have shaped modern clinical trial design[10].

One of the most significant contributions of the journal was the publication of the first adaptive trial design in 1995. The adaptive design allows for modifications to the trial protocol based on interim data analysis, which can save time and resources and improve the chances of success. The publication of this study paved the way for the adoption of adaptive trial designs in modern clinical research. The journal also played a crucial role in the development of non-inferiority trials, which are used to demonstrate that a new treatment is not worse than an established treatment by a predetermined margin. The first non-inferiority trial published in the Annals of Clinical Trials was the ISIS-2 trial, which showed that aspirin was as effective as streptokinase in the treatment of acute myocardial infarction.

Another significant development in clinical trial design was the emergence of cluster randomized trials, which are used to evaluate interventions at the group level rather than the individual level. The Annals of Clinical Trials published some of the earliest cluster randomized trials, including the study on the effectiveness of water filtration systems in reducing diarrhea in children in Bangladesh. Ethical considerations have always been an essential aspect of clinical research. The Annals of Clinical Trials has been a vocal advocate for ethical standards in clinical research and has published several studies on ethical considerations in clinical trial design.

One of the most notable studies on ethical considerations was the publication of the Helsinki Declaration, which outlines ethical principles for medical research involving human subjects. The Helsinki Declaration has become the foundation for ethical standards in clinical research and has been updated several times since its initial publication in 1964.The journal has also played a crucial role in promoting informed consent as a fundamental ethical principle in clinical research. The publication of the first study on informed consent in clinical research in the Annals of Clinical Trials in 1972 set the stage for the adoption of informed consent as a standard practice in clinical research. Clinical trials have played a significant role in modern medicine. They have been used to test the safety and effectiveness of new treatments, procedures, and diagnostic tools before they are approved for use in the general population. Clinical trials have evolved over the centuries from anecdotal evidence to rigorous studies that follow a standardized protocol. In this article, we will take a brief look at the history of clinical trials, their development, and their current state.

The first recorded clinical trial was conducted by the Scottish naval surgeon James Lind in 1747. He tested the effectiveness of various remedies for scurvy on sailors on board the HMS Salisbury. The trial was not randomized, and the sample size was small, but it did show that citrus fruit was effective in preventing and treating scurvy. However, it took over a century for randomized controlled trials (RCTs) to become a standard for clinical research.In the mid-20th century, the need for RCTs became evident as drugs and medical devices became more complex and required rigorous testing. The first RCTs were conducted in the 1940s, and they quickly became the gold standard for clinical research. The introduction of ethical guidelines, such as the Nuremberg Code in 1947, further improved the quality of clinical trials.

In the 1960s and 1970s, clinical trials began to expand beyond testing new drugs and devices. Researchers began using clinical trials to test different treatment strategies and to explore the effectiveness of interventions such as behavioral therapy and lifestyle changes. This led to the development of pragmatic clinical trials, which are designed to test interventions in real-world settings. Another development was the emergence of phase trials, which are conducted in different stages to test the safety and effectiveness of a treatment. Phase I trials are conducted with a small number of healthy volunteers to test the safety of the treatment. Phase II trials are conducted with a larger group of people to test the effectiveness of the treatment. Phase III trials are conducted with an even larger group of people to confirm the effectiveness of the treatment and to compare it with existing treatments. Finally, phase IV trials are conducted after the treatment has been approved to monitor its long-term safety and effectiveness.

Today, clinical trials are more rigorous than ever before. They are designed to minimize bias and to ensure that the results are reliable and valid. The Consolidated Standards of Reporting Trials (CONSORT) guidelines, developed in 1996, provide a standardized protocol for conducting and reporting clinical trials. The guidelines cover everything from the design of the study to the statistical analysis of the data. Clinical trials are also subject to strict ethical guidelines. The Declaration of Helsinki, developed in 1964, provides ethical guidelines for medical research involving human subjects. In the United States, clinical trials are overseen by the Institutional Review Board (IRB), which ensures that the study meets ethical guidelines and that the rights and welfare of the participants are protected.

Conclusion

The Annals of Clinical Trials has been an integral part of the evolution of clinical trials over the past century. Clinical trials have come a long way since James Lind’s scurvy trial in the 18th century. They have evolved from anecdotal evidence to rigorous studies that follow a standardized protocol. The development of ethical guidelines and the introduction of randomized controlled trials have greatly improved the quality of clinical research. Today, clinical trials are more rigorous than ever before, and they are subject to strict ethical guidelines the rise of patient-centered outcomes. Clinical trials are also becoming more patient-centric. Patientcentered outcomes research (PCOR) is a relatively new approach to clinical research that focuses on the outcomes that matter most to patients. PCOR studies are designed to provide patients with the information they need to make informed decisions about their healthcare.

Acknowledgement

None

Conflict of Interest

None

References

1. Nickel T, Hanssen H, Sisic Z et al. Immunoregulatory effects of the flavonol quercetin in vitro and in vivo. European Journal of Nutrition. 50, 163-172 (2011).

Google Scholar, Crossref, Indexed at

2. Moro T, Shimoyama Y, Kushida M et al. Glycyrrhizin and its metabolite inhibit Smad3-mediated type I collagen gene transcription and suppress experimental murine liver fibrosis. Life Sciences. 83, 531-539 (2008).

Google Scholar, Crossref, Indexed at

3. Kolasa KM, Rickett K. Barriers to providing nutrition counselling cited by physicians. Nutrition in Clinical Practice. 25, 502-509 (2010).

Google Scholar, Crossref, Indexed at

4. Glanz K. Review of nutritional attitudes and counselling practices of primary care physicians. American Journal of Clinical Nutrition. 65, 2016-2019 (1997).

Google Scholar, Crossref, Indexed at

5. Holeček M. Nutritional modulation of liver regeneration by carbohydrates, lipids, and amino acids. Nutrition. 15, 784-788 (1999).

Google Scholar, Crossref, Indexed at

6. Nishiura T, Watanabe H, Ito M et al. Ultrasound evaluation of the fibrosis stage in chronic liver disease by the simultaneous use of low and high frequency probes. British Journal of Radiology. 78, 189-197 (2005).

Google Scholar, Crossref, Indexed at

7. Ma CX, Luo J, Ellis MJ et al. Molecular profiling of triple negative breast cancer. Breast Disease. 32, 73-84 (2010).

Google Scholar, Crossref, Indexed at

8.  Ellis MJ, Ding L, Shen D et al. Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature. 486, 353-360 (2012).

Google Scholar, Crossref, Indexed at

9. Perou CM. The genomic landscape of breast cancer as a therapeutic roadmap. Cancer Discovery. 3, 27-34 (2013).

Google Scholar, Crossref, Indexed at

10. Wang H, Mao X. Evaluation of the efficacy of neoadjuvant chemotherapy for breast cancer. Drug Design, Development and Therapy. 14, 2423-2433 (2020).

Google Scholar, Crossref, Indexed at