From the Guidelines
Groundbreaking clinical trials, such as the International Study of Infarct Survival (ISIS), Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto (GISSI), and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trials, have revolutionized cardiology and transformed clinical practice. These trials have demonstrated significant benefits in reducing morbidity and mortality, and have led to the development of new treatment standards 1.
Some key features of groundbreaking clinical trials include:
- Large sample sizes to generate reliable outcomes
- Sufficient follow-up duration to capture the full benefits of interventions
- Rigorous methodology to establish efficacy and safety profiles
- A focus on modifying major cardiovascular risk factors, such as hypertension and dyslipidaemia
The impact of these trials can be seen in the significant reduction in cardiovascular events and mortality rates over the past few decades 1. However, despite these advances, there is still a need to identify additional effective therapies and to increase upstream prevention and precision medicine efforts.
Recent examples, such as the proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibiting monoclonal antibodies, have shown the importance of prolonged follow-up in capturing the full benefits of interventions 1. The conduct of large trials with sufficient follow-up duration is crucial in realizing the full potential of new therapies and improving patient outcomes.
In the context of real-life clinical medicine, it is essential to prioritize the conduct of high-quality trials that can provide reliable evidence for treatment decisions, while also addressing the regulatory and financial barriers that hinder the conduct of trials, particularly for interventions with little or no commercial support 1.
From the Research
Definition of Groundbreaking Clinical Trials
- Groundbreaking clinical trials refer to randomized controlled trials (RCTs) that provide high-quality evidence for the effectiveness and safety of an intervention 2.
- These trials are considered the gold standard in clinical research, as they aim to determine whether a cause-effect relation exists between an intervention and an outcome 2.
Characteristics of Groundbreaking Clinical Trials
- Prospective, comparative, and quantitative study/experiment performed under controlled conditions with random allocation of interventions to comparison groups 2.
- High-quality evidence can be generated by performing an RCT when evaluating the effectiveness and safety of an intervention 2.
- RCTs yield themselves well to systematic review and meta-analysis, providing a solid base for synthesizing evidence generated by such studies 2.
Limitations and Challenges
- High-quality evidence from RCTs is often incomplete, contradictory, or absent even in areas that have been most exhaustively studied 3.
- The likelihood of the success or failure of a therapy is not identical in all individuals treated in any trial, and the overall results of a trial cannot be assumed to apply to any particular individual 3.
- The potential for bias due to financial conflicts remains in many guideline groups, and clinicians must still reason through the best choices for an individual 3.
- Designing and conducting an RCT, analyzing data, interpreting findings, and disseminating results can be challenging, with several practicalities to be considered 2.
Alternative Approaches
- In the absence of clinical trials, alternative approaches such as proportional meta-analysis of case series studies can provide some evidence of the intervention's effects under evaluation 4.
- Although these alternative approaches lead to a low level of evidence, they can help surgeons, physicians, and health professionals make provisionally informed decisions in healthcare, along with their clinical expertise and the patient's wishes and circumstances 4.