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Open-label trial

An open-label trial is a type of clinical trial in which both the researchers and participants are fully aware of the treatment or intervention being administered to the participants.^[1] This contrasts with blinded trials, where knowledge of the treatment assignment is withheld from one or both parties to minimize bias in assessment and reporting.^[2] Open-label trials are commonly employed when full blinding is infeasible, such as in long-term safety assessments of approved drugs.^[3] These trials can be randomized or non-randomized, single-arm (where all participants receive the same treatment) or multi-arm (comparing different known treatments), but they do not inherently imply a lack of control or structure.^[2] Key uses include evaluating the long-term effects, tolerability, and real-world effectiveness of therapies after initial blinded phases, as well as extension studies following randomized controlled trials to monitor ongoing safety.^[3] For instance, they are valuable for comparing two approved drugs with similar mechanisms when blinding is challenging due to distinct administration methods or side effect profiles.^[3] Despite their utility, open-label designs carry risks of bias, as awareness of treatment can influence participant expectations, adherence, and subjective outcome reporting, potentially affecting data integrity.^[2] To mitigate this, trial designs emphasize objective endpoints, blinded independent assessors where possible, identical procedures across arms, and pre-specified statistical analysis plans.^[2] Advantages include feasibility in scenarios where blinding would compromise ethics or practicality.^[3] Overall, open-label trials play a critical role in clinical research by providing essential data on treatment applicability while necessitating rigorous methods to ensure reliability.^[2]

Definition and Characteristics

Definition

An open-label trial is a type of clinical trial in which neither the participants nor the investigators are blinded to the treatment allocation, allowing all parties to know whether an individual is receiving the active intervention, placebo, or comparator treatment.^[4]^[5] This design contrasts with blinded trials by forgoing any concealment of treatment identity, which is a core strategy in general clinical research to reduce observer and participant bias during efficacy and safety assessments.^[6] The lack of blinding in open-label trials emphasizes transparency in treatment administration but highlights the defining role of non-concealment, differing from the broader aim of clinical trials to control for subjective influences in outcome evaluation.^[7] In contrast to randomized controlled trials that often incorporate blinding to enhance objectivity, open-label approaches are selected when masking is impractical, such as for treatments with distinct appearances or administration methods.^[8]

Key Features

In open-label trials, both participants and researchers are fully aware of the treatment being administered, eliminating any form of blinding or masking of the intervention.^[9] This transparency extends to the absence of placebo arms in many designs, where all participants typically receive the active treatment, allowing for direct observation of its effects without deception.^[3] Such overt disclosure distinguishes open-label trials from blinded studies, as the identity of the intervention is known throughout the trial duration.^[10] Treatment assignment in open-label trials is conducted without concealment of the allocation from participants or investigators, though randomization may still be employed to distribute participants across groups.^[3] When randomization occurs, it serves to balance groups but does not hide the treatment details post-assignment, enabling adjustments based on known interventions while exposing the process to potential influences from awareness.^[9] This overt assignment process contrasts with concealed methods in blinded designs, prioritizing visibility over minimization of expectation effects.^[11] Data collection in open-label trials emphasizes observable and patient-reported outcomes, including adverse events, treatment adherence, and real-world intervention responses, with comprehensive logging tied to the known treatments.^[3] Investigators document these elements in detail, often incorporating clinician and participant perceptions to capture the unmasked impact of the therapy.^[9] This approach facilitates tracking of long-term patterns, such as persistence of effects, without the need for coded or disguised data interpretation.^[10] Open-label trials vary structurally, with single-arm designs providing all participants the same known intervention for preliminary assessment, lacking a comparator group.^[11] In contrast, multi-arm open-label trials involve multiple known treatment groups, sometimes randomized, to compare active therapies directly while maintaining transparency across arms.^[3] These variations allow flexibility in evaluating interventions under unblinded conditions, tailored to the trial's objectives.^[10]

Design and Methodology

Trial Phases and Types

Open-label trials are integrated into specific phases of clinical drug development, particularly where blinding is impractical, unethical, or unnecessary for the objectives. They are commonly used in Phase II trials for dose-finding and preliminary efficacy assessment, allowing investigators and participants to openly administer escalating doses while monitoring safety and tolerability in patient cohorts larger than Phase I but smaller than confirmatory phases. In Phase III, open-label designs often appear as extensions to blinded randomized controlled trials (RCTs), enabling the collection of long-term safety and efficacy data beyond the primary endpoint period. Phase IV, or post-marketing surveillance, frequently employs open-label trials to evaluate real-world performance, identify rare adverse events, and assess effectiveness in broader populations after regulatory approval.^[12]^[13]^[14] Within open-label trials, several subtypes address distinct needs in clinical research. Extension trials serve as follow-on studies to blinded RCTs, permitting participants who benefited from the investigational treatment to continue receiving it under open conditions, thereby generating extended safety profiles and durability of response data. Compassionate use or open-access studies provide continued access to investigational therapies for patients who have completed prior trials or face serious unmet needs, often outside formal regulatory pathways but under oversight to ensure ethical treatment delivery. Exploratory open-label trials are particularly suited to rare diseases, where small patient pools and ethical constraints limit blinded designs, focusing instead on initial signals of benefit in uncontrolled settings.^[15]^[16]^[17] Open-label trials can be structured as single-arm or comparative designs, each tailored to the research question. Single-arm open-label trials involve a single treatment group without concurrent controls, emphasizing direct observation of treatment effects, adverse events, and response rates, which is advantageous when historical data or ethical considerations preclude randomization. Comparative open-label trials incorporate multiple arms, such as an investigational treatment versus a known active comparator, to contextualize efficacy while maintaining transparency in administration and assessment.^[2]^[2] In terms of duration and scale, open-label trials often extend over longer periods—frequently years—compared to the typical 1–3 years for primary phases of blinded RCTs, as seen in extension studies that prioritize chronic condition monitoring. They generally enroll smaller cohorts in extension and exploratory designs, ranging from dozens to a few hundred participants, while pragmatic comparative open-label trials may involve thousands; this contrasts with the thousands in large blinded RCTs, with selection criteria that stress safety evaluation, patient retention, and bias minimization through standardized follow-up rather than broad generalizability.^[13]^[9]^[18]

Implementation Procedures

The implementation of an open-label trial begins with the development of a detailed protocol that explicitly outlines the overt treatment arms, ensuring all procedures—such as visit schedules, adverse event collection, and inclusion/exclusion criteria—are identical across arms except for the treatment itself.^[2] Informed consent processes must emphasize full disclosure of known risks, benefits, and the open-label nature of the study, describing procedures including treatment assignments in clear, understandable language to minimize coercion and enable voluntary participation.^[19] To mitigate bias inherent in the unblinded design, protocols incorporate strategies like allocation concealment—preventing prediction of assignments—randomization methods clearly specified in advance, and standardized assessments by blinded endpoint evaluators where feasible.^[2] Participant enrollment proceeds without deception regarding blinding, involving transparent screening based on consistent criteria and full disclosure of the assigned treatment to eligible individuals.^[2] Once enrolled, participants are monitored in real-time for adherence, side effects, and overall safety, with protocols requiring consistent follow-up of all randomized subjects who maintain consent, including those who discontinue treatment early, to reduce differential missing data across arms.^[2] Data management in open-label trials relies on transparent logging systems to record all observations without concealment, often utilizing electronic data capture tools to ensure accessibility and auditability while restricting interim data access to independent data monitoring committees (DMCs) and designated statisticians.^[2] Statistical analysis accounts for the absence of blinding by employing intention-to-treat (ITT) principles on all randomized subjects, evaluating patterns of missing data for potential bias, and applying treatment policy strategies for intercurrent events, without adjustments specifically for allocation concealment since assignments are known.^[2] Endpoint selection prioritizes safety and tolerability measures, such as adverse event rates and discontinuation due to toxicity, which are assessed consistently across arms using blinded reviewers or adjudication committees when possible to limit observer bias.^[2] Secondary efficacy endpoints, like symptom improvement or response rates, are selected cautiously, favoring objective outcomes over subjective ones to interpret results amid potential placebo effects or expectation biases, with protocols finalizing these in a pre-specified statistical analysis plan.^[2]

Advantages and Disadvantages

Advantages

Open-label trials offer reduced logistical complexity compared to blinded designs, as they eliminate the need for specialized blinding materials, allocation codes, or dummy treatments, which simplifies administration, lowers costs, and accelerates study initiation.^[20] This approach is particularly practical when blinding is infeasible due to the nature of the interventions, such as surgical procedures or devices that cannot be concealed.^[2] These trials facilitate enhanced safety monitoring, enabling researchers and clinicians to immediately identify and intervene in adverse events since treatment assignments are known to all parties involved.^[21] This transparency is especially beneficial in long-term studies or those involving high-risk populations, where prompt adjustments to dosing or discontinuation can mitigate potential harms.^[22] From an ethical standpoint, open-label designs align with principles of informed consent by avoiding any deception regarding treatment allocation, which is crucial in life-threatening conditions where withholding active therapy could cause harm.^[20] For instance, in oncology trials for serious cancers, using placebos is often unethical when effective standard therapies exist, making open-label formats a preferable alternative to ensure patients receive potentially beneficial interventions without delay.^[23] Additionally, open-label trials provide greater real-world relevance by capturing authentic patient-provider interactions, which can yield more accurate data on treatment adherence, tolerability, and impacts on quality of life outside controlled, artificial settings.^[24] This mirrors everyday clinical practice, where knowledge of the treatment influences patient behavior and reporting, thereby enhancing the applicability of findings to routine care.^[21]

Disadvantages

Open-label trials are particularly susceptible to various forms of bias due to the absence of blinding, which allows both participants and researchers to know the treatment allocation. Placebo effects can be amplified as participants, aware of receiving the active intervention, may report improved symptoms driven by expectations rather than the treatment itself.^[25] Similarly, observer bias arises when investigators, knowing the treatment, unconsciously favor positive interpretations of outcomes, such as subjective assessments of efficacy or side effects.^[26] Expectation effects further compound this, as both parties' preconceived notions about the treatment's benefits can alter behavior and reporting, inflating perceived efficacy.^[27] Participant behavior may also change in response to this knowledge, such as increased adherence or lifestyle modifications motivated by optimism, which distorts the true treatment impact.^[28] The lack of blinding in open-label trials limits the ability to establish causal inference, even when control groups are included, making it challenging to distinguish treatment effects from the natural progression of the disease or external factors. Without blinding, outcomes are more prone to confounding, reducing the robustness of evidence for attributing improvements solely to the intervention.^[2] Open-label trial results are often considered less robust for definitive regulatory approval of efficacy compared to blinded randomized controlled trials, as authorities like the FDA prioritize the latter for their superior control over variables and bias minimization.^[2] Recruitment in open-label trials can introduce self-selection bias, as potential participants who are aware of the active treatment may be more inclined to enroll if they have strong preferences or expectations, leading to a non-representative sample. This skews demographics, such as favoring more motivated or less severe cases, which undermines the generalizability of findings to broader populations. Such selection effects can further exacerbate imbalances in baseline characteristics, complicating interpretations and reducing external validity. To counteract these biases, open-label trials often demand additional resources for bias control measures, such as adopting strictly objective endpoints like survival rates or imaging biomarkers, which require specialized equipment and expertise. Independent monitors or central review committees may also be necessary to oversee assessments and ensure impartiality, increasing logistical and financial costs that can offset the perceived simplicity of the design.^[29] These requirements, including enhanced data monitoring and statistical adjustments, can strain trial budgets and timelines without fully eliminating the risks inherent to the open-label format.^[2]

Comparison to Blinded Trials

Differences from Single-Blind Trials

Open-label trials differ from single-blind trials primarily in the extent of knowledge regarding treatment allocation among participants and researchers. In single-blind designs, only the participants remain unaware of whether they are receiving the active treatment or a control, while investigators and study staff have full knowledge to ensure proper administration and management of interventions.^[7] This asymmetry allows researchers to make objective decisions without participant influence but introduces potential for observer bias. In contrast, open-label trials disclose the treatment assignments to both participants and researchers from the outset, eliminating any masking and thereby increasing the risk of interaction-based biases where expectations from either party could influence outcomes.^[9] The bias profiles of these trial types reflect their differing levels of transparency. Single-blind trials effectively mitigate participant expectation bias, as individuals cannot alter their behavior or reporting based on known treatment, though they are susceptible to observer bias where knowledgeable researchers might unconsciously favor certain outcomes through subtle influences in assessment or data interpretation.^[30] Open-label trials, however, expose both types of bias, as participants' awareness can lead to placebo-like effects or differential adherence, while researchers' knowledge may amplify subjective endpoint evaluations, particularly in trials relying on patient-reported measures.^[26] Studies have shown that lack of participant blinding in non-double-blind designs, including open-label, can overestimate treatment effects by up to 20-30% in subjective outcomes compared to more blinded approaches.^[31] Use cases for these designs align with their ability to handle specific intervention challenges. Single-blind trials are particularly suited to psychological or behavioral studies, where blinding participants reduces expectancy effects on self-reported symptoms, but full blinding of therapists or assessors is often impractical due to the interactive nature of the interventions.^[32] For instance, in trials evaluating cognitive behavioral therapy, single-blinding participants helps isolate treatment efficacy from demand characteristics. Open-label trials, meanwhile, are better adapted to overt physical interventions such as surgical adjuncts or procedures where masking is infeasible, as treatments like distinct implantations or dosing regimens cannot be concealed without compromising safety or ethics.^[33] In such contexts, transparency facilitates informed consent and real-world applicability. In terms of evidence hierarchy, both designs fall below double-blind randomized controlled trials due to incomplete bias control, but single-blind trials generally rank higher than open-label ones for minimizing placebo and expectation effects. Systematic reviews indicate that single-blind approaches reduce performance and detection biases more effectively than fully transparent designs, providing stronger causal inference in comparative effectiveness research, though both require rigorous methods like allocation concealment to enhance validity.^[7] Open-label trials, while valuable for feasibility, are often positioned lower in evidence pyramids for efficacy claims, reserved for supportive or safety data generation.^[31]

Differences from Double-Blind Trials

Open-label trials differ fundamentally from double-blind trials in their approach to blinding, which is considered the gold standard for minimizing bias in clinical research. In double-blind trials, neither participants, investigators, nor outcome assessors are aware of the treatment assignments, achieved through mechanisms such as randomization codes, identical placebos, and sham procedures that conceal the intervention from all relevant parties.^[2]^[34] This full concealment enables an unbiased assessment of efficacy and safety by preventing expectation effects, adherence differences, and interpretive biases that could otherwise influence results. In contrast, open-label trials involve complete transparency, where both participants and investigators know the assigned treatments, compromising this protective layer and increasing the risk of subjective influences on trial conduct and data interpretation.^[8]^[2] Regarding scientific validity, double-blind trials provide stronger causal evidence, particularly for pivotal Phase III studies required for regulatory approvals, as they reduce performance, detection, and attrition biases to establish treatment effects reliably.^[9]^[34] These designs are routinely employed to demonstrate efficacy in drug development because they yield more objective outcomes compared to non-blinded alternatives.^[8] Open-label trials, however, are generally limited to supportive or exploratory roles, such as early-phase safety assessments or situations where blinding is infeasible (e.g., surgical interventions), due to their heightened susceptibility to bias that weakens inferential strength.^[2]^[8] Their findings often require corroboration from prior blinded studies to inform regulatory decisions. Operationally, double-blind trials demand substantial logistical complexity, including the development of indistinguishable formulations, strict allocation concealment, and independent data monitoring committees to maintain blinding integrity throughout the study.^[2]^[34] This overhead ensures consistency in procedures across arms but can increase costs and recruitment challenges. Open-label trials simplify these aspects by eliminating the need for such deceptions, allowing for straightforward administration and ethical transparency, though this ease comes at the expense of methodological rigor and potential for differential treatment handling.^[8]^[2] In terms of outcome reliability, double-blind trials substantially mitigate all major sources of bias, leading to more trustworthy data on endpoints like symptom improvement or adverse events, with studies showing reduced exaggeration in participant-reported outcomes (e.g., by up to 0.56 standard deviations in non-blinded scenarios).^[34] Open-label designs, while useful for real-world applicability, often produce data prone to overestimation of benefits due to unmitigated biases in retention, reporting, and analysis, necessitating additional safeguards like blinded assessors or objective measures—and even then, results typically need validation from blinded precedents.^[2]^[34]

Applications and Examples

Common Applications

Open-label trials are frequently utilized in clinical research scenarios where blinding is impractical or unnecessary, allowing for transparent administration of treatments while focusing on specific objectives like safety monitoring and practical implementation. These designs are particularly valuable in post-approval settings and specialized therapeutic areas, enabling researchers to gather robust data under real-world conditions without the logistical complexities of masking interventions.^[15] A prominent application involves long-term safety studies, especially for chronic conditions such as HIV and oncology, where open-label trials support post-approval monitoring to detect rare adverse events that may only emerge after years of exposure. In these studies, participants receive the treatment openly over extended durations, often spanning several years, to assess tolerability and identify low-incidence risks that blinded trials might overlook due to shorter timelines. This approach is essential for ongoing pharmacovigilance, as it leverages larger cohorts and prolonged follow-up to inform regulatory updates and clinical guidelines. For instance, in HIV management, open-label extensions have been instrumental in evaluating the sustained safety profile of antiretroviral therapies beyond initial approval phases. Similarly, in oncology, where treatments like immunotherapies require long-term observation, open-label designs track cumulative toxicities in chronic use.^[35]^[36] Extension phases represent another core use, typically following double-blind randomized controlled trials to provide continued access to promising therapies for participants while amassing real-world efficacy data. After the blinded phase concludes, eligible patients transition to an open-label period, often lasting months to years, which helps bridge the gap between controlled efficacy demonstrations and broader post-marketing surveillance. This setup not only maintains treatment continuity but also captures long-term outcomes in a less controlled environment, revealing practical insights into adherence, dosing adjustments, and effectiveness outside ideal trial conditions. Such extensions are standard in drug development pipelines, enhancing the overall evidence base for approval and labeling decisions.^[15]^[13] Open-label trials are also commonly applied in the development of treatments for rare diseases and orphan drugs, where ethical constraints preclude placebo use and limited patient pools restrict recruitment for larger blinded studies. In these contexts, the design demonstrates treatment feasibility by openly administering the intervention to small cohorts, focusing on preliminary safety, pharmacokinetics, and clinical activity to support accelerated regulatory pathways. For example, in infectious diseases, approximately 63% of pivotal trials leading to orphan drug approvals (2010-2020) featured open-label formats, often non-randomized, to ethically evaluate interventions in populations with unmet needs. This application is particularly suited to conditions where withholding treatment could cause harm, allowing direct assessment of benefits in real-time without the biases or infeasibilities of blinding.^[37]^[38] Furthermore, early Phase II trials frequently employ open-label designs for dose optimization, enabling iterative adjustments to regimens based on immediate feedback from patients and clinicians without the constraints of blinding. This facilitates rapid escalation, de-escalation, or modification of doses to identify the optimal balance of efficacy and tolerability, often through sequential cohorts or adaptive protocols. By removing masking, investigators can promptly address side effects or response patterns, streamlining development for therapies requiring personalized dosing, such as in oncology or infectious diseases. This method aligns with regulatory emphases on efficient dose-finding to minimize patient burden while maximizing therapeutic potential.^[39]^[40]

Notable Examples

One prominent historical example of an open-label trial occurred during the 1980s AIDS crisis with zidovudine (AZT), the first antiretroviral drug approved for HIV treatment. In 1985, a phase I open-label trial involving 18 patients with AIDS demonstrated AZT's potential to improve symptoms and immune function, providing initial safety data amid the epidemic's urgency where no effective therapies existed.^[41] Following a phase II double-blind trial stopped early in 1986 due to clear survival benefits, all participants were unblinded and offered open-label AZT access, enabling early treatment for hundreds while generating long-term survival and toxicity data that informed post-approval monitoring.^[41] This approach was driven by ethical pressures from AIDS activists advocating for compassionate use, leading to expanded access programs that treated thousands outside formal trials by 1987.^[42] In the 2020s, open-label trials played a key role in evaluating COVID-19 vaccine boosters after initial blinded phase III studies, particularly in assessing waning immunity and responses to variants like Omicron. A 2021-2022 phase 2 open-label trial of the mRNA-1273 booster in 344 previously vaccinated adults showed robust increases in neutralizing antibodies against SARS-CoV-2 variants, including Beta and Delta, countering observed declines in protection from primary series doses over 6 months.^[43] These studies, conducted post-emergency use authorization, confirmed booster safety and immunogenicity without controls, supporting real-world rollout amid evolving viral threats and providing data on durable humoral and cellular responses beyond initial blinded efficacy endpoints.^[43] In oncology, the long-term open-label follow-up of imatinib (Gleevec) in chronic myeloid leukemia (CML) highlighted durable treatment effects extending from earlier efficacy assessments. The phase III IRIS trial, initiated in 2000 as an open-label comparison of imatinib versus interferon plus cytarabine in 1,106 newly diagnosed chronic-phase CML patients, transitioned to continuous open-label imatinib for responders; a 5-year follow-up reported complete cytogenetic responses in 87% and major cytogenetic responses in 92% of imatinib-treated patients, with 93% progression-free survival and minimal transformation to advanced disease.^[44] This extended monitoring, without blinding in the follow-up phase, revealed sustained complete molecular responses in over 40% of patients by year 5, establishing imatinib's role in long-term disease control and informing tyrosine kinase inhibitor standards beyond initial blinded or controlled phases.^[44] For rare diseases, an open-label phase I trial of nusinersen in spinal muscular atrophy (SMA) focused on safety in pediatric populations lacking suitable controls due to ethical and disease rarity constraints. Conducted from 2011 to 2014 in 28 children aged 2 to 15 years with types II or III SMA, the trial administered single intrathecal doses up to 9 mg and found no serious drug-related adverse events, with stable or improved motor function in most participants over 14 months.^[45] This uncontrolled design provided critical tolerability data, including pharmacokinetics and platelet monitoring, paving the way for larger confirmatory studies and approval in 2016 for treating infantile-onset SMA in infants and children.^[45]

Ethical and Regulatory Aspects

Ethical Considerations

Open-label trials emphasize transparency in treatment allocation, which enhances informed consent by providing participants with full disclosure about the interventions they receive, thereby respecting their autonomy and minimizing elements of deception inherent in blinded designs. This approach aligns with ethical principles that prioritize voluntary participation based on complete understanding, as participants are informed of the study's open nature, potential risks, and lack of blinding, allowing them to make decisions without misleading information. In cases involving serious illnesses, open-label trials promote equitable access by avoiding placebo controls when effective treatments exist, upholding the principle of beneficence and preventing harm from withholding proven therapies. The Declaration of Helsinki specifies that placebos may only be used if no proven intervention is available or for compelling methodological reasons where short-term delays pose no serious risk, making open-label designs ethically preferable to ensure all participants receive active treatment in such scenarios. However, the transparency of open-label trials introduces risks of bias, as awareness of treatment can influence participant expectations, adherence, and subjective outcome reporting, potentially affecting data integrity and raising concerns about voluntariness of consent, particularly among vulnerable populations. Institutional Review Boards (IRBs) play a crucial role in oversight, requiring rigorous scrutiny of open-label protocols to evaluate bias potential and confirm that the design is justified over blinded alternatives, ensuring participant protection and scientific integrity. IRBs must verify that measures to minimize bias, such as allocation concealment and objective endpoints, are implemented to safeguard against ethical lapses in vulnerable groups.

Regulatory Guidelines

Regulatory bodies worldwide have established specific guidelines for the design, conduct, and reporting of open-label clinical trials to mitigate inherent biases and ensure scientific integrity. In the United States, the Food and Drug Administration (FDA) issued a 2023 draft guidance titled "Considerations for Open-Label Clinical Trials: Design, Conduct, and Analysis," which emphasizes the need to acknowledge potential biases in trial protocols and prioritize objective endpoints to minimize subjective influences on outcomes.^[2] This document highlights that while open-label designs are appropriate for certain scenarios, such as extension studies or when blinding is impractical, sponsors must implement strategies like randomization and independent adjudication committees to reduce risks of detection and performance bias.^[2] In Europe, the European Medicines Agency (EMA) aligns with International Council for Harmonisation (ICH) standards, particularly ICH E9 on Statistical Principles for Clinical Trials, which requires description of the blinding status (including open-label designs) in protocols and reports, along with steps to minimize bias such as using objective primary variables.^[20] Under these harmonized guidelines, open-label trials must detail efforts to minimize known sources of bias and include sensitivity analyses to assess the impact of unblinding on results.^[20] The EMA further enforces these through its Clinical Trials Regulation (EU) No 536/2014, mandating comprehensive protocol submissions that address bias mitigation in non-blinded designs. Reporting of open-label trials is governed by the CONSORT 2025 (Consolidated Standards of Reporting Trials) statement, updated in April 2025, which requires explicit disclosure of limitations arising from the absence of blinding, including potential placebo effects and observer bias, to facilitate critical appraisal by readers and regulators.^[46] Specifically, CONSORT item 20a mandates description of blinding (or lack thereof) after assignment to interventions and measures to minimize bias if blinding was not possible, while item 29 calls for discussion of trial limitations, ensuring that publications transparently address how the open-label nature may affect generalizability and validity.^[46] Internationally, the World Health Organization (WHO) through its Global Research and Innovation for Health Emergencies framework recommends open-label randomized controlled trials for urgent global health crises, as outlined in its 2023 report, with post-2020 updates emphasizing adaptive designs to accelerate responses during pandemics like COVID-19.^[47] These guidelines stress ethical integration with regulatory standards, allowing open-label approaches when blinding poses logistical barriers in emergency settings, provided bias controls are robustly documented.^[47]

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Blinding, or “masking”, is the process by which information that has the potential to influence study results is withheld from one or more parties involved in ...
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Long-Term Safety from the Raltegravir Clinical Development Program
Raltegravir has demonstrated potent and durable efficacy and a favorable safety profile in 3 phase III studies in treatment-naïve and treatment-experienced ...Missing: oncology | Show results with:oncology
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Detection bias in open-label trials of anticancer drugs
Aug 16, 2023 · Open-label trials are more common in oncological clinical trials than in non-oncological trials, and there has been a trend towards using ...
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Evaluation of clinical trials done for orphan drugs versus nonorphan ...
Nonrandomized (58%), open-labeled (63%) studies with a small sample size were the predominant feature of the pivotal trials for orphan approvals. More than half ...
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Pivotal Studies of Orphan Drugs Approved for Neurological Diseases
The US Food and Drug Administration has approved orphan drugs for neurological diseases without randomized, doubled-blind, placebo-controlled pivotal trials.
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Dose optimization during drug development: whether and when to ...
The goal of dose optimization during drug development is to identify a dose that preserves clinical benefit with optimal tolerability.<|control11|><|separator|>
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Adaptive phase 2/3 design with dose optimization - ScienceDirect.com
FDA's Project Optimus initiative for oncology drug development emphasizes selecting a dose that optimizes both efficacy and safety.
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AIDS Drug AZT: How It Got Approved 30 Years Ago | TIME
Mar 19, 2017 · The first AIDS drug was approved on March 19, 1987—but getting there was by no means easy. Here's the story behind the treatment.Missing: open- label
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Historical Perspective - Expanding Access to Investigational ... - NCBI
A brief review of earlier approaches to expanded access and a summary of the drug approval process prior to the start of the AIDS epidemic.
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Immune response to SARS-CoV-2 after a booster of mRNA-1273
Mar 3, 2022 · These findings with variants and waning immunity after two doses of mRNA vaccines suggest that a booster vaccine injection might be beneficial.Missing: studies 2020s<|separator|>
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Five-Year Follow-up of Patients Receiving Imatinib for Chronic ...
After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high ...
[49]
Results from a phase 1 study of nusinersen (ISIS-SMN Rx ) in ...
This study provides Class IV evidence that in children with SMA, intrathecal nusinersen is not associated with safety or tolerability concerns.
[50]
ARE OPEN-LABEL PLACEBOS ETHICAL? INFORMED CONSENT ...
We conclude that open placebos fulfil current American Medical Association guidelines for placebo use, and propose future research directions for harnessing ...
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A systematic qualitative review of ethical issues in open label ...
Apr 10, 2025 · The use of placebos in clinical practice has traditionally been a subject of ethical controversy due to several reasons: It often involves ...
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[PDF] Global Research and Innovation for Health Emergencies
Oct 13, 2023 · Clinical research in the context of outbreaks and pandemics ... Open-label randomized controlled trials. (RCTs) during outbreaks are feasible and.