Adaptive trial design: Its growing role in clinical research and implications for pharmacists

Cirulli, Joshua; McMillian, Wesley D.; Saba, Mojdeh; Stenehjem, David D.

doi:10.2146/ajhp100298

Cited by 7 publications

(4 citation statements)

References 15 publications

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“…Additional time is necessary to fully tackle technical and logistical issues such as: programming language to handle adaptive designs within study databases and other data management issues; training of sites; strategies to maintain blinding; drug supply estimation; management of study drug inventory, and other pharmacy issues. 20, 21 The additional time and upfront development costs raise questions as to the feasibility of designing adaptive design trials without external funding to support the required infrastructure and expertise, even within the framework of a well-funded project such as ADAPT-IT. While planning and development in the pharmaceutical industry has direct funding from within the pharmaceutical company, specific funding streams for the development phase of an adaptive clinical trial are more difficult to establish in academic settings.…”

Section: Discussionmentioning

confidence: 99%

A conceptual model for the development process of confirmatory adaptive clinical trials within an emergency research network

et al. 2017

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Background Adaptive clinical trials use accumulating data from enrolled subjects to alter trial conduct in pre-specified ways based on quantitative decision rules. In this research, we sought to characterize the perspectives of key stakeholders during the development process of confirmatory phase adaptive clinical trials within an emergency clinical trials network, and to build a model to guide future development of adaptive clinical trials. Methods We used an ethnographic, qualitative approach to evaluate key stakeholders’ views about the adaptive clinical trial development process. Stakeholders participated in a series of multidisciplinary meetings during the development of five adaptive clinical trials, and completed a Strengths-Weaknesses-Opportunities-Threats questionnaire. In the analysis, we elucidated overarching themes across the stakeholders’ responses to develop a conceptual model. Results Four major overarching themes emerged during the analysis of stakeholders’ responses to questioning: the perceived statistical complexity of adaptive clinical trials, and the roles of collaboration, communication, and time during the development process. Frequent and open communication and collaboration were viewed by stakeholders as critical during the development process, as were the careful management of time and logistical issues related to the complexity of planning adaptive clinical trials. Conclusions The Adaptive Design Development Model illustrates how statistical complexity, time, communication and collaboration are moderating factors in the adaptive design development process. The intensity and iterative nature of this process underscores the need for funding mechanisms for the development of novel trial proposals in academic settings

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Section: Discussionmentioning

confidence: 99%

A conceptual model for the development process of confirmatory adaptive clinical trials within an emergency research network

et al. 2017

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“…Finally, in this trial, we also adopted an adaptive design, which is defined as a study that includes a prospectively planned opportunity for the modification of one or more specified aspects of the study design and hypotheses based on the analysis of accumulating data (usually interim data) from subjects in the study [ 36 ]. This method will make the study more efficient (e.g., have a shorter duration or include fewer patients) and is more likely to demonstrate an effect of the drug if one exists [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Danhong injection in the treatment of chronic stable angina: study protocol for a randomized controlled trial

Wang

Dong

et al. 2015

Trials

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BackgroundChronic stable angina is a leading cause of death worldwide. Danhong injection, a complementary alternative medicine for chronic stable angina, has been demonstrated to be effective in numerous studies and is widely prescribed to patients. However, the methodological quality of most prior studies was found to be, in general, low. Therefore, we designed this randomized controlled trial to evaluate the efficacy and safety of using Danhong injection to treat chronic stable angina.Methods/designThis is a randomized multicentre, double-blind, placebo-controlled, adaptive clinical trial. A total of 870 patients meeting the eligibility criteria will be randomly assigned into either the Danhong injection or the placebo group in a 2:1 ratio. Participants will then undergo a 2-week treatment regimen and a 76-day follow-up period. Because this is an adaptive trial, two interim analyses are prospectively planned. These will be performed after one-third and two-thirds of the patients, respectively, have completed the trial. Based on the results of these interim analyses, a data monitoring committee will determine how to modify aspects of the study without undermining the validity and integrity of the trial. The primary outcome measure is the proportion of patients who show a clinically significant change, which is defined as at least a 20-point improvement in angina frequency score on the Seattle Angina Questionnaire, which will be administered on day 30. Other secondary efficacy and safety outcomes will also be assessed.DiscussionThis trial will provide high-quality evidence regarding the use of Danhong injection to treat chronic stable angina.Trial registrationClinicalTrials.gov: NCT01681316.

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“…The wrapped dropping bottles and brown transfusion devices will be used to facilitate the placebo control, making the treatment seemingly identical between the DHI and placebo groups, so the potential placebo effect will be excluded. Besides, an adaptive design, which includes a prospectively planned opportunity for modification of the trial design, has been adopted to improve the efficiency of the study (e.g., shorter duration, or fewer patients) [ 19 ]. Moreover, the add-on study design, which can be summarized as “A + B versus B” model, will also be applied in this trial.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the effects of Danhong injection in treatment of acute ischemic stroke: study protocol for a multicenter randomized controlled trial

Wang

et al. 2015

Trials

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BackgroundDanhong injection (DHI) has been widely prescribed to patients with acute ischemic stroke (AIS). However, due to methodological deficiencies, previous research has not yet provided rigorous evidence to support the use of DHI in the treatment of AIS. Therefore, we designed this multicenter, randomized, controlled, and double-blind trial to evaluate the efficacy and safety of DHI for AIS.Methods/DesignIt is a randomized, multicenter, double-blind, placebo-controlled, adaptive clinical trial. A total of 864 eligible patients will be randomized into either the DHI or placebo group in a 2:1 ratio. All patients will be given the standard medical care as recommended by guidelines. Participants will undergo a 2-week treatment regimen and 76-day follow-up period. The primary outcome is the proportion of patients with a favorable outcome, defined as a score of 0–1 on the modified Rankin scale at day 90. Secondary outcomes include a change in the total score of the Chinese medicine symptom scales of “Xueyu Zheng” (blood stasis syndrome), the proportion of patients with a Barthel Index score of ≥90, the proportion of patients with an improvement in NIHSS score of ≥4 or NIHSS score of 0–1, quality of life measured by the EQ-5D scale, etc. Safety outcomes such as global disability (mRS ≥3) at day 90 will also be assessed. The changes in mRNA and microRNA profiles in 96 patients selected from certain centers will also be assessed. As this is an adaptive design, two interim analyses are prospectively planned, which will be carried out after one-third and two-thirds of patients have completed the trial, respectively. Based on the results of the interim analyses, the Data Monitoring Committee (DMC) will decide how to modify the study.DiscussionThis trial will provide high-quality evidence for DHI in treatment of AIS.Trial registrationClinical Trials.gov NCT01677208 (Date of registration 22 December 2012).Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-1076-4) contains supplementary material, which is available to authorized users.

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Adaptive trial design: Its growing role in clinical research and implications for pharmacists

Abstract: Adaptive trial design is an emerging study methodology that allows for design modifications during a study, with the objective of implementing trial data as early as possible for the benefit of patients and the drug development process.

Cited by 7 publications

References 15 publications

A conceptual model for the development process of confirmatory adaptive clinical trials within an emergency research network

A conceptual model for the development process of confirmatory adaptive clinical trials within an emergency research network

Danhong injection in the treatment of chronic stable angina: study protocol for a randomized controlled trial

Evaluating the effects of Danhong injection in treatment of acute ischemic stroke: study protocol for a multicenter randomized controlled trial

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