A new path for CF clinical trials through the use of historical controls

Laparoscopy has been introduced as a minimally invasive approach that has been developed to achieve the intended outcomes by open surgeries but with less frequent body injuries and complications. However, evidence indicates that the reported favourable outcomes are mainly based on retrospective data and using historical controls and only a few prospective investigations and clinical trials were published. Furthermore, studies have also demonstrated that following laparoscopy, severe pain can develop similar to or equal to the pain reported during open surgeries that develop within the earliest hours due to the significant tissue trauma introduced by laparoscopy. The present literature review discussed the different causes and types of chronic pain following laparoscopy. We also shed more light on the potential mechanisms and pathophysiology that attributes to the development of pain following laparoscopy. Many studies have indicated the development of chronic pain after 3, 6 and 12 months after hysterectomy, cholecystectomy, nephrectomy, colorectal surgeries and other abdominal surgeries. The development of postoperative main might be attributed to the tissue or nerve injury and associated inflammatory status that can also aid to the development of pain in such settings. Evidence also shows that the incidental pain following laparoscopy is similar or superior to that following open surgeries. Therefore, further interventional approaches are needed to enhance the outcomes.

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Historical Controls

PEDIATRICS ◽

10.1542/peds.70.1.145 ◽

1982 ◽

Vol 70 (1) ◽

pp. 145-147

Author(s):

V. T. Farewell

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Experimental Design ◽

Scientific Experiment ◽

Clinical Investigations ◽

Considerable Period ◽

Historical Controls

The use of concurrent controls in clinical trials has been advocated for a considerable period of time and by a large number of researchers. Nevertheless, the nature of clinical investigations appears to lead to continuing interest in the use of historical controls. The two opposing views are enunciated in papers by Byar et al1 and Gehan and Freireich.2 When a clinical trial is viewed as a scientific experiment, the use of concurrent controls, and especially randomized concurrent controls, is to be preferred based on long-standing principles of experimental design. There is little doubt that the ethics of clinical experimentation rightly impose constraints on what might otherwise be viewed as ideal experimental design.

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So Much Data, So Little Knowledge: Using Formal Logic to Aggregate Data and Interpret Information

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_209527 ◽

2018 ◽

pp. e2-e5

Author(s):

J. Russell Hoverman

Keyword(s):

Clinical Trials ◽

Randomized Clinical Trials ◽

Retrospective Studies ◽

Formal Logic ◽

Competing Values ◽

Professional Societies ◽

Large Databases ◽

Patient Values ◽

Meta Analyses ◽

Historical Controls

Formal logic is the use of symbols to structure how we make inferences such that the structure can be applied beyond specific cases. The structure of clinical trials and the values equation (value = outcomes/cost) lend themselves to evaluation using formal logic. Doing this demonstrates the unique position of randomized clinical trials as a defensible format for gathering information and identifies the shortcomings of historical controls and meta-analyses and retrospective studies using large databases. A practical example using literature on maintenance therapy in metastatic colorectal cancer is assessed. It is important to emphasize that value will be relative to a viewpoint, with many interested parties having competing values. This underscores the place of physicians and professional societies as putting patient values first.

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Reducing Patient Burden in Clinical Trials Through the Use of Historical Controls: Appropriate Selection of Historical Data to Minimize Risk of Bias

Therapeutic Innovation & Regulatory Science ◽

10.1007/s43441-019-00014-4 ◽

2019 ◽

Vol 54 (4) ◽

pp. 850-860 ◽

Cited By ~ 1

Author(s):

Jessica Lim ◽

Li Wang ◽

Nicky Best ◽

Jeen Liu ◽

Jiacheng Yuan ◽

...

Keyword(s):

Clinical Trials ◽

Historical Data ◽

Risk Of Bias ◽

Historical Controls ◽

Patient Burden ◽

Selection Of

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Sensitivity and specificity of clinical trials. Randomized v historical controls

Archives of Internal Medicine ◽

10.1001/archinte.143.4.753 ◽

1983 ◽

Vol 143 (4) ◽

pp. 753-755 ◽

Cited By ~ 19

Author(s):

H. S. Sacks

Keyword(s):

Clinical Trials ◽

Sensitivity And Specificity ◽

Historical Controls

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Creating a synthetic control arm from previous clinical trials: Application to establishing early end points as indicators of overall survival in acute myeloid leukemia (AML).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.7021 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 7021-7021 ◽

Cited By ~ 2

Author(s):

Donald A. Berry ◽

Michael Elashoff ◽

Steven Blotner ◽

Ruthie Davi ◽

Philip Beineke ◽

...

Keyword(s):

Overall Survival ◽

Clinical Trials ◽

Phase I ◽

Synthetic Control ◽

Eligibility Criteria ◽

End Points ◽

Investigational Agent ◽

Experimental Drugs ◽

Adaptive Clinical Trials ◽

Historical Controls

7021 Background: Clinical trials of experimental drugs require controls. Concurrently randomized controls are the gold standard for judging drug effect. Historical controls are not ideal but are much more efficient and economical. Historical controls derived from a single clinical trial have the biases of that trial. Using many trials with comparable end points and eligibility minimizes such bias. Medidata’s archive contains >3000 trials with clinical data rights for deidentified aggregated analyses. We used this resource to develop a synthetic control arm (SCA) for a particular phase I/II single-arm trial in AML. We demonstrate the utility of this approach by addressing a different but equally important issue: establishing early end points as predictors of long term clinical outcomes. Methods: We built an SCA from 7 relapsed/refractory AML trials completed in last 5 yrs. They had similar eligibility criteria as a particular phase I/II trial for an investigational agent. We selected subjects for the SCA who had baseline covariates matching the subjects in the tri.al. Data cleaning and standardization ensured consistency of data fields. The primary outcomes were CR (complete remission) and CRi (CR without hematologic recovery) at 56 days, and overall survival (OS) subsequent to 56 days. Non-CR/non-CRi deaths before 56 days were set to OS=0. We used a landmark analysis to correlate CR and CRi with OS, calculating the hazard ratio (HR) of OS of CR and CRi vs its comparison group. Results: The SCA included 340 subjects (median age 63 yrs, 55% male, 77% White Non-Hispanic, 28% ECOG 0). Results are in this table. Conclusions: The Medidata trial archive is a resource for creating SCAs. The example SCA we created identified well-defined subjects for whom a CR or CRi is associated with longer OS. Investigations of SCAs for other drugs could aid in addressing the types of subjects and drug categories for which CR or CR/CRi predict longer OS. Such information can help build more efficient and more informative adaptive clinical trials. [Table: see text]

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