Time to See the Difference: Video Capture for Patient-Centered Clinical Trials

AbstractIn the approval process for new weight management therapies, regulators typically require estimates of effect size. Usually, as with other drug evaluations, the placebo-adjusted treatment effect (i.e., the difference between weight losses with pharmacotherapy and placebo, when given as an adjunct to lifestyle intervention) is provided from data in randomized clinical trials (RCTs). At first glance, this may seem appropriate and straightforward. However, weight loss is not a simple direct drug effect, but is also mediated by other factors such as changes in diet and physical activity. Interpreting observed differences between treatment arms in weight management RCTs can be challenging; intercurrent events that occur after treatment initiation may affect the interpretation of results at the end of treatment. Utilizing estimands helps to address these uncertainties and improve transparency in clinical trial reporting by better matching the treatment-effect estimates to the scientific and/or clinical questions of interest. Estimands aim to provide an indication of trial outcomes that might be expected in the same patients under different conditions. This article reviews how intercurrent events during weight management trials can influence placebo-adjusted treatment effects, depending on how they are accounted for and how missing data are handled. The most appropriate method for statistical analysis is also discussed, including assessment of the last observation carried forward approach, and more recent methods, such as multiple imputation and mixed models for repeated measures. The use of each of these approaches, and that of estimands, is discussed in the context of the SCALE phase 3a and 3b RCTs evaluating the effect of liraglutide 3.0 mg for the treatment of obesity.

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Selection Of The Most Appropriate Epro Mode: Contributing To The Success Of Patient-Centered Clinical Trials

Value in Health ◽

10.1016/j.jval.2016.03.1703 ◽

2016 ◽

Vol 19 (3) ◽

pp. A108-A109

Author(s):

J Ross ◽

E Holzbaur ◽

T Rothrock

Keyword(s):

Clinical Trials ◽

Patient Centered ◽

Selection Of

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CLINICAL TRIALS IN INFANTS OF ORALLY ADMINISTERED ATTENUATED POLIOMYELITIS VIRUSES

PEDIATRICS ◽

10.1542/peds.23.6.1041 ◽

1959 ◽

Vol 23 (6) ◽

pp. 1041-1062

Author(s):

Stanley Alan Plotkin ◽

Hilary Koprowski ◽

Joseph Stokes

Keyword(s):

Clinical Trials ◽

Fecal Excretion ◽

Jackson Type ◽

Poliomyelitis Virus ◽

Minor Illness ◽

The Difference ◽

Antibody Levels ◽

Type 3

Forty-six infants, ranging from less than 1 day to 6 months of age, were given more than 100 feedings of living, attenuated poliomyelitis viruses without the occurrence of major or minor illness. The strains used were CHAT (type 1), Wistar (type 1), Jackson (type 2), P-712 (type 2) and Fox (type 3). All strains except the Jackson strain were found to be antigenic on oral administration. Response to vaccination was demonstrated in these infants by the presence after vaccination of antibody levels significantly in excess of those attributable to transplacentally acquired antibodies, and by the detection of fecal excretion of poliomyelitis virus. Infants less than 2 months old were more difficult to immunize than older infants. The evidence suggests that biologic immaturity rather than transplacental antibodies caused the difference. When the three types of poliomyelitis virus were fed at 3-week intervals, responses occurred to all types. No interference between types was observed when they were fed in all possible sequences. Three infants given a second feeding of homotypic, attenuated poliomyelitis virus 3 to 5 months after a successful vaccination showed resistance to intestinal reinfection.

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Review of the efficacy of placebo in comparative clinical trials between typical and atypical antipsychotics

Brazilian Journal of Psychiatry ◽

10.1590/s1516-44462009000100013 ◽

2009 ◽

Vol 31 (1) ◽

pp. 52-56 ◽

Cited By ~ 5

Author(s):

Irismar Reis de Oliveira ◽

Paulo Menezes Nunes ◽

Domingos Macedo Coutinho ◽

Eduardo Pondé de Sena

Keyword(s):

Clinical Trials ◽

Atypical Antipsychotic ◽

Atypical Antipsychotics ◽

Rating Scale ◽

Study Drug ◽

Typical Antipsychotic ◽

The Difference ◽

Psychiatric Rating Scale ◽

Efficacy Parameters ◽

Typical Antipsychotics

OBJECTIVE: To review the efficacy of placebo in comparison with atypical and typical antipsychotics for the treatment of schizophrenia and schizoaffective disorder and to evaluate the pertinence of using placebo in clinical trials with antipsychotics. METHOD: Trials in which the atypical antipsychotics were compared with typical antipsychotics and placebo were included. A search was conducted using the terms "amisulpride", "aripiprazole", "clozapine", "olanzapine", "quetiapine", "risperidone", "sertindole", "ziprasidone" and "zotepine". Main efficacy parameters were calculated using the proportion of "events" (defined as a deterioration or lack of improvement by at least 20% in Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale) and the pooled relative risk with random effects, with their respective 95% confidence intervals. We also calculated the necessary sample sizes in studies in which the study drug is compared to a typical antipsychotic or placebo. RESULTS: The pooled efficacy rates observed were 40.8%, 34.9% and 21.3% for the atypical antipsychotics, typical antipsychotics and placebo, respectively. One hundred and sixty six patients would have to be included when a new drug is compared with placebo if calculation is based on a difference of 20% found between the atypical antipsychotic and placebo and 2,054 if the difference sought were that found between the atypical antipsychotic and the typical antipsychotic, i.e. 6%. The estimated therapeutic failures would be 115 of the 166 patients when the study drug is compared with placebo, and 1,274 failures in the 2,054 patients when the study drug is compared to the typical antipsychotic. CONCLUSIONS: Placebo controlled studies may reduce the number of individuals exposed to the harmful effects of ineffective drugs.

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Improving the External Validity of Clinical Trials: The Case of Multiple Chronic Conditions

Journal of Comorbidity ◽

10.15256/joc.2013.3.27 ◽

2013 ◽

Vol 3 (2) ◽

pp. 30-35 ◽

Cited By ~ 6

Author(s):

Fortin Martin ◽

Smith M. Susan

Keyword(s):

Clinical Trials ◽

External Validity ◽

Chronic Conditions ◽

Evidence Base ◽

Specific Reference ◽

Multiple Chronic Conditions ◽

Patient Centered ◽

Department Of Health ◽

Patient Groups ◽

Intervention Trials

The U.S. Department of Health and Human Services vision and strategic framework on multiple chronic conditions (MCCs) incorporates recommendations designed to facilitate research that will improve our knowledge about interventions and systems that will benefit individuals with MCCs (or multimorbidity). The evidence base supporting the management of patients with MCCs will be built through intervention trials specifically designed to address multimorbidity and identification of MCCs in participants across the clinical trial range. This article specifically focuses on issues relating to external validity with specific reference to trials involving patients with MCCs. The exclusion of such patients from clinical trials has been well documented. Randomized control trials (RCTs) are considered the “gold standard” of evidence, but may have drawbacks in relation to external validity, particularly in relation to multimorbidity. It may, therefore, be necessary to consider a broader range of research methods that can provide converging evidence on intervention effects to address MCCs. Approaches can also be taken to increase the usefulness of RCTs in general for providing evidence to inform multimorbidity management. Additional improvements to RCTs would include better reporting of inclusion and exclusion criteria and participant characteristics in relation to MCCs. New trials should be considered in terms of how they will add to the existing evidence base and should inform how interventions may work in different settings and patient groups. Research on treatments and interventions for patients with MCCs is badly needed. It is important that this research includes patient-centered measures and that generalizability issues be explicitly addressed.

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Making Clinical Trials More Patient-Centered Using Digital Interactive E-Consent Tools

10.3768/rtipress.2019.op.0063.1910 ◽

2019 ◽

Author(s):

Barbara Biesecker ◽

Melissa Raspa ◽

Douglas Rupert ◽

Rebecca Moultrie ◽

Robert Furberg ◽

...

Keyword(s):

Clinical Trials ◽

Informed Choice ◽

Consent Process ◽

Delivery Mode ◽

Compelling Evidence ◽

Patient Centered ◽

Research Participants ◽

Informed Decisions ◽

Potential Benefits ◽

Participant Understanding

Research participants are required to give their consent to participate in clinical trials and nonexempt government-funded studies. The goal is to facilitate participant understanding of the intent of the research, its voluntary nature, and the potential benefits and harms. Ideally, participants make an informed choice whether to participate; one that is based on having sufficient relevant knowledge and that is consistent with their values and preferences. Achieving this objective can be challenging, and as such, many scholars have declared the consent process flawed or “broken.” Moreover, clinical trials are complex studies, and compelling evidence suggests that current consent processes are inadequate in achieving informed choice. E-consent offers a dynamic, engaging consent delivery mode that can effectively support making informed decisions about whether to participate in a trial.

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Patient-centered assessments: how can they be used in dental clinical trials?

Brazilian Oral Research ◽

10.1590/1807-3107bor-2020.vol34.0075 ◽

2020 ◽

Vol 34 (suppl 2) ◽

Cited By ~ 1

Author(s):

Matheus França PERAZZO ◽

Júnia Maria SERRA-NEGRA ◽

Ramon Targino FIRMINO ◽

Isabela Almeida PORDEUS ◽

Paulo Antônio MARTINS-JÚNIOR ◽

...

Keyword(s):

Clinical Trials ◽

Patient Centered

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International Dermatology Outcome Measures Initiative as Applied to Psoriatic Disease Outcomes: An Update

The Journal of Rheumatology ◽

10.3899/jrheum.160114 ◽

2016 ◽

Vol 43 (5) ◽

pp. 959-960 ◽

Cited By ~ 5

Author(s):

Joseph F. Merola ◽

April W. Armstrong ◽

Ami Saraiya ◽

John Latella ◽

Amit Garg ◽

...

Keyword(s):

Clinical Trials ◽

Clinical Practice ◽

Outcome Measures ◽

Treatment Efficacy ◽

Regulatory Agencies ◽

Washington Dc ◽

Patient Centered ◽

Psoriatic Disease ◽

Disease Outcomes ◽

Dermatologic Disease

Previous publications have described the International Dermatology Outcome Measures (IDEOM) group, comprising patients, physicians, health economists, participating pharmaceutical industry partners, payers, and regulatory agencies. The goal of IDEOM is to create patient-centered, validated measures of dermatologic disease progression and treatment efficacy for use in both clinical trials and clinical practice. We provide an update of IDEOM activities as of our 2015 IDEOM meeting in Washington, DC, USA.

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Q-TWiST analysis of tivozanib (T) versus sorafenib (S) in patients with advanced renal cell carcinoma (RCC) in the TIVO-3 study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.298 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 298-298

Author(s):

Michael Szarek ◽

Michael N. Needle ◽

Brian I. Rini ◽

Sumanta K. Pal ◽

David F. McDermott ◽

...

Keyword(s):

Progression Free Survival ◽

Phase Iii ◽

P Value ◽

Patient Centered ◽

Health States ◽

Significant Difference ◽

Phase Iii Study ◽

The Difference ◽

Similar Survival ◽

Mean Differences

298 Background: In the randomized phase III study TIVO-3, the VEGFR-TKI tivozanib (TIVO) increased progression-free survival with better tolerability but no difference in overall survival (OS) relative to sorafenib (SORA) as third- or fourth-line therapy in patients with metastatic RCC. These results provide motivation to apply quality-adjusted time without symptoms of disease and toxicity (Q-TWiST) methods to quantify the net health benefits of TIVO, in the presence of similar survival, when compared to SORA. Methods: In application of Q-TWiST, patient-level OS was subdivided into three mutually exclusive states: time with toxicity (TOX), time without symptoms and toxicity (TWiST), and time after progression/relapse (REL). Mean Q-TWiST was calculated by applying utility coefficients of 0.5, 1.0, and 0.5 to the restricted mean (max 36 months follow-up) health states of TOX, TWiST, and REL, respectively; 95% CIs for the means and mean differences were estimated by bootstrap distributions. Relative Q-TWiST gain was defined as the mean absolute Q-TWiST difference divided by the SORA mean OS. Results: Mean TWiST was significantly longer for TIVO than for SORA (10.30 months v.5.35 months; Table). Mean REL time was significantly shorter for TIVO, with no difference in mean TOX time. Mean Q-TWiST was 15.04 and 12.78 months for TIVO and SORA, respectively, a statistically significant difference (p=0.0493). The relative gain for TIVO was 11.2%. Clinical trial information: NCT02627963 . Values in table are mean (95% CI) in months or p-value for difference in treatment group means. Conclusions: The difference in Q-TWiST in TIVO-3 was primarily driven by benefits of TIVO in TWiST, partially offset by superiority of SORA in REL time. As a third- or fourth-line treatment for RCC, TIVO significantly increased Q-TWiST relative to SORA, primarily through an increase in TWiST, which is generally considered to be the state with highest utility to patients. Consequently, Q-TWiST may be considered an alternative patient-centered measure of benefit of TIVO in these settings. [Table: see text]

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Dare voce ai pazienti nella ricerca sulle malattie rare e sui famaci orfani / Giving patients a voice in the rare diseases and orphan drugs research

Medicina e Morale ◽

10.4081/mem.2018.526 ◽

2018 ◽

Vol 67 (1) ◽

pp. 25-40

Author(s):

Elena Mancini ◽

Roberta Martina Zagarella

Keyword(s):

Clinical Trials ◽

Rare Diseases ◽

Patient Reported Outcomes ◽

Narrative Medicine ◽

Orphan Drugs ◽

New Drugs ◽

Patient Centered ◽

Patient Reported ◽

Critical Issues ◽

The Impact

L’articolo ha l’obiettivo di mettere in luce potenzialità e criticità dell’inclusione della prospettiva dei pazienti nella ricerca sulle malattie rare e sui farmaci orfani. A tal fine, nella prima parte, si propone un’analisi epistemologica dell’utilizzo dei racconti dell’esperienza individuale della malattia nella ricerca scientifica e nei trial clinici, facendo emergere, anche attraverso gli strumenti della medicina narrativa, le sfide teoriche e operative poste dall’inclusione della soggettività del paziente e del vissuto di malattia nonché l’importanza della valorizzazione della prospettiva del paziente, sia in generale sia nella ricerca sulle malattie rare e sui farmaci orfani. Nella seconda parte, il testo analizza in particolare il ruolo degli esiti riportati dai pazienti o Patient Reported Outcomes (PROs), misure per la valutazione complessiva della salute basate sulla prospettiva dei pazienti stessi, incentrandosi sulla sperimentazione clinica nel campo delle malattie rare. In questo contesto, infatti, i racconti di malattia, raccolti e valorizzati da fonti istituzionali e associazioni di pazienti, hanno contribuito a far emergere importanti questioni critiche e difficoltà nell’impiego di outcome centrati sul paziente nello sviluppo di nuovi farmaci e trattamenti, generando una serie di documenti e raccomandazioni relative al loro utilizzo per il benessere della comunità dei malati rari. ---------- This paper aims to highlight the potentiality and criticality of including patients’ perspective in rare diseases and orphan drugs research. In the first part, we propose an epistemological analysis of individual narrations of disease experience as they are used in scientific research and clinical trials. With the help of narrative medicine approach, this analysis points out theoretical and operational challenges of a perspective that includes patient’s subjectivity and illness experience. Furthermore, it reveals the significance of patients’ standpoints in general and in rare diseases as well as in the orphan drugs research. The second part of our article focuses on the role of the Patient reported Outcomes (PROs) – which are measures for the health’s overall assessment based on patient’s perspective – by investigating the impact on clinical trials for rare diseases. In this context, illness stories, which are collected and promoted by institutional sources and patients’ associations, contribute to underline important critical issues at stake in the employment of patient-centered outcomes both in new drugs and in the treatments development. Moreover, these stories are crucial to elaborate documents and recommendations concerning the use of PROs for the rare patients’ community welfare.

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