Pivotal Trials

Extracted Attributes

• Typical Phase

  Phase III

• Alternative Name

  Registration studies

• Participant Range

  300 to 3,000 subjects

• Median Cost (2017)

  $19 million USD

• Statistical Power Threshold

  Adverse effect rate of not less than 1 in 100 subjects

• Median Duration (Medical Devices)

  3 years

Timeline

• Start of the analysis period for medical device pivotal trials which showed a median duration of three years. (Source: Wikipedia)

  2006-01-01

• End of the analysis period for medical device pivotal trials concluding that an additional two years were typically needed for FDA review. (Source: Wikipedia)

  2013-12-31

• The median cost of a pivotal trial across all clinical indications in the United States was recorded at $19 million. (Source: Wikipedia)

  2017-01-01

• FDA Commissioner Marty Makary discusses reforms at the JP Morgan Healthcare Conference, including reducing the default number of pivotal trials from two to one. (Source: Document 065d2e96-4d40-49bd-8511-d8d35f8b01f4)

  2025-01-13

Pivotal trial

A pivotal trial is typically a Phase III clinical trial in the multi-year process of clinical research intended to demonstrate and confirm the safety and efficacy of a treatment – such as a drug candidate, medical device or clinical diagnostic procedure – and to estimate the incidence of common adverse effects. A successful pivotal trial is required as evidence for drug marketing approval by the relevant approval authorities, such as the European Medicines Agency, Health Canada or United States Food and Drug Administration (FDA). In drug research, a pivotal Phase III trial may be referred to as a "therapeutic confirmatory study", and is conducted in a large number (hundreds to thousands) of subjects. Such pivotal trials are also designed to discover and estimate the prevalence of common adverse events, but based on their size only have the statistical power to establish an adverse effect rate of not less than 1 in 100 subjects. In an analysis of pivotal trials on medical devices conducted between 2006 and 2013, the median duration was three years, with another two years needed for FDA review and approval for marketing. In 2017 in the United States, the median cost of a pivotal trial across all clinical indications was US$19 million. The cost of a pivotal trial increased when more subjects were added to clarify a treatment effect, when active drug comparators were used to improve understanding of the trial drug characteristics, or when specific clinical endpoints were measured rather than using surrogate outcomes.

Web Search Results

• What Is a Pivotal Trial? - Lindus Health

  ## Defining a Pivotal Trial A pivotal trial is a large and statistically robust study designed to demonstrate the efficacy and safety of a new medical intervention when compared to a control, typically a placebo or an existing treatment. These trials are often conducted after preliminary evidence suggests that the intervention could be beneficial, and they provide the data needed for regulatory approvals. ### The Basics of Pivotal Trials In essence, pivotal trials primarily focus on collecting comprehensive data over a specified period to assess outcomes that are crucial for regulatory submissions. These trials involve a relatively large patient population to ensure that the results are statistically significant and can be generalized to the broader population. [...] ## Conclusion In conclusion, pivotal trials are a fundamental component of clinical research, playing a decisive role in the development of new treatments and devices. By utilizing structured methodologies, adhering to regulatory requirements, and leveraging the expertise of contract research organizations, researchers can conduct effective and ethical pivotal trials that ultimately benefit public health. [...] Pivotal trials are a cornerstone of clinical research, particularly in the development and approval of new drugs and medical devices. These trials gather essential data that can determine a product's market viability and safety. Understanding what a pivotal trial entails and its significance in the overall research process is crucial for stakeholders, including researchers, regulatory bodies, and healthcare professionals. ## Defining a Pivotal Trial

• Pivotal trial - Wikipedia

  Type of clinical research trial A pivotal trial is typically a Phase III clinical trial in the multi-year process of clinical research intended to demonstrate and confirm the safety and efficacy of a treatment – such as a drug candidate, medical device or clinical diagnostic procedure – and to estimate the incidence of common adverse effects. A successful pivotal trial is required as evidence for drug marketing approval by the relevant approval authorities, such as the European Medicines Agency, Health Canada or United States Food and Drug Administration (FDA). [...] In drug research, a pivotal Phase III trial may be referred to as a "therapeutic confirmatory study", and is conducted in a large number (hundreds to thousands) of subjects. Such pivotal trials are also designed to discover and estimate the prevalence of common adverse events, but based on their size only have the statistical power "Power (statistics)") to establish an adverse effect rate of not less than 1 in 100 subjects. In an analysis of pivotal trials on medical devices conducted between 2006 and 2013, the median duration was three years, with another two years needed for FDA review and approval for marketing. [...] In 2017 in the United States, the median cost of a pivotal trial across all clinical indications was US$19 million. The cost of a pivotal trial increased when more subjects were added to clarify a treatment effect, when active drug comparators were used to improve understanding of the trial drug characteristics, or when specific clinical endpoints were measured rather than using surrogate outcomes. ## References [edit]

• FAQs on Pivotal Clinical Trials - Quanticate

  In many development programmes, pivotal clinical trials are Phase III studies that compare the new treatment with placebo or standard of care in a defined patient population. However, phase and pivotal status are not identical. In some cases, particularly in areas such as oncology or rare diseases, a well-designed Phase II study can be considered pivotal if it is sufficiently robust in terms of design, sample size, and clinical relevance. For example, a randomised, controlled Phase II trial with a meaningful endpoint and strong effect size may be used as the main evidence for approval, especially where disease prevalence makes larger studies difficult. Pivotal trials sit between early development and post-marketing work: [...] ## What is 'pivotal' in medical terms? “Pivotal” refers to the decisive role these trials play in regulatory decision-making process. As mentioned, the results support a marketing authorisation application to agencies such as the FDA, EMA, or MHRA. Regulators rely heavily on pivotal trial data when they assess benefit–risk, consider product labelling, and decide whether to approve a treatment for routine clinical use. Earlier phase studies explore safety, dosing, and signals of efficacy. By contrast, pivotal trials also termed as ‘registration studies’ are confirmatory. They follow a pre-agreed protocol, use pre-specified endpoints, and apply statistical methods that have been discussed with regulators in advance. [...] Before pivotal trials, Phase I and early Phase II studies establish basic safety, pharmacokinetics, dosing, and initial signs of efficacy. Pivotal trials provide the confirmatory evidence required for regulatory assessment. After approval, post-marketing or Phase IV studies may explore long-term outcomes, rare safety events, or use in broader populations. ## How are pivotal studies designed? The design of a pivotal clinical trial must support clear, interpretable conclusions. Typical features include:

• What is a Pivotal Clinical Trial? Understanding Its Importance

  General ## Introduction Pivotal clinical trials are integral to the development and approval of new drugs and treatments, providing essential evidence on their safety and efficacy. These meticulously designed studies, often guided by regulatory bodies such as the FDA's Center for Drug Evaluation and Research (CDER), compare new interventions against existing treatments or placebos. By doing so, they ensure a comprehensive evaluation of therapeutic benefits, which is critical for regulatory approval and public use. [...] ## Conclusion Pivotal clinical trials serve as a cornerstone in the development and approval of new drugs and treatments, providing essential evidence of their safety and efficacy. These meticulously designed studies, characterized by rigorous methodologies and extensive sample sizes, facilitate a comprehensive evaluation of new interventions against existing treatments or placebos. The role of regulatory bodies, particularly the FDA, is crucial in guiding these trials, ensuring adherence to stringent standards that ultimately protect public health. [...] Furthermore, pivotal trials offer strong proof that backs the bioequivalence of generic medications to their brand-name equivalents, an essential element in regulatory decision-making. According to the FDA, bioequivalence requires that there be no significant differences between test and reference medications in key pharmacokinetic parameters, such as time to maximum concentration and the area under the concentration-time curve. This rigorous evaluation process ensures that both new and existing medications meet high standards of quality, safety, and efficacy before they reach the market.

• Step 3: Clinical Research - FDA

  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 Phase 4 Image 8 Study Participants: Several thousand volunteers who have the disease/condition Purpose:Safety and efficacy [...] 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 Phase 2 Image 6 Study Participants:Up to several hundred people with the disease/condition. Length of Study:Several months to 2 years [...] 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. Clinical Research Phase Studies Phase 1 Image 5 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.