Dataset Information

Placebo Response to Oral Administration in Osteoarthritis Clinical Trials and Its Associated Factors: A Model-Based Meta-analysis.

ABSTRACT:

Importance

In osteoarthritis (OA) clinical trials, a placebo is often used as control. Therefore, a thorough understanding of the placebo response is important for guiding drug development in OA.

Objective

To develop an oral placebo response model for OA.

Data sources

PubMed, EMBASE, and Cochrane Library databases were searched systematically from January 1, 1991, to July 2, 2022.

Study selection

Randomized double-blind placebo-controlled trials of patients with primary OA were included. The interventions and placebo were administered orally. A total of 3032 trials were identified; of these, 130 (4.3%) met the inclusion criteria.

Data extraction and synthesis

Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, dosage form of the placebo, sample size, proportion of patients who previously used nonsteroidal anti-inflammatory drugs, publication year, intervention categories, Kellgren-Lawrence grades, proportion of White patients, duration of pain, funding source, and risk of bias were extracted. A model-based meta-analysis was used to evaluate the time course of the placebo response in OA treatment and estimate the influencing factors. For subgroup analyses, a meta-analysis with a random-effects model was used to summarize the typical values of the model parameters and their SEs.

Main outcomes and measures

The primary end point was the time course of the oral placebo response on the WOMAC pain, stiffness, and function subscale scores.

Results

The 130 trials selected for analysis included 12 673 participants (mean age, 59.9 years; 68.9% women). The baseline scores of WOMAC pain, stiffness, and function subscales were found to be significantly associated with the placebo response. The placebo response reached 90% of its maximum response between 5 and 7 weeks. The placebo responses on the WOMAC subscales were also associated with the sample size, proportion of patients who had previously used nonsteroidal anti-inflammatory drugs, intervention drugs, and publication year.

Conclusions and relevance

In this study, an oral placebo response model of OA was developed that may quantitatively describe the placebo response at different baseline levels of symptoms. The findings may provide valuable references for future clinical trial design and decision-making.

SUBMITTER: Wen X

PROVIDER: S-EPMC9552894 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Placebo Response to Oral Administration in Osteoarthritis Clinical Trials and Its Associated Factors: A Model-Based Meta-analysis.

Wen Xin X Luo Jieren J Mai Yiying Y Li Yang Y Cao Ying Y Li Zewei Z Han Shun S Fu Quanyi Q Zheng Qingshan Q Ding Changhai C Zhu Zhaohua Z Li Lujin L

JAMA network open 20221003 10

<h4>Importance</h4>In osteoarthritis (OA) clinical trials, a placebo is often used as control. Therefore, a thorough understanding of the placebo response is important for guiding drug development in OA.<h4>Objective</h4>To develop an oral placebo response model for OA.<h4>Data sources</h4>PubMed, EMBASE, and Cochrane Library databases were searched systematically from January 1, 1991, to July 2, 2022.<h4>Study selection</h4>Randomized double-blind placebo-controlled trials of patients with prim ...[more]

PMID: 36215072

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Project description:ImportanceAntidepressants are commonly used to treat major depressive disorder (MDD). Antidepressant outcomes can vary based on individual differences; however, it is unclear whether specific factors determine this variability or whether it is at random.ObjectiveTo investigate the assumption of systematic variability in symptomatic response to antidepressants and to assess whether variability is associated with MDD severity, antidepressant class, or study publication year.Data sourcesData used were updated from a network meta-analysis of treatment with licensed antidepressants in adults with MDD. The Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, and PsycInfo were searched from inception to March 21, 2019. Additional sources were international trial registries and sponsors, drug companies and regulatory agencies' websites, and reference lists of published articles. Data were analyzed between June 8, 2020, and June 13, 2020.Study selectionAnalysis was restricted to double-blind, randomized placebo-controlled trials with depression scores available at the study's end point.Data extraction and synthesisBaseline means, number of participants, end point means and SDs of total depression scores, antidepressant type, and publication year were extracted.Main outcomes and measuresLog SDs (bln σ̂) were derived for treatment groups (ie, antidepressant and placebo). A random-slope mixed-effects model was conducted to estimate the difference in bln σ̂ between treatment groups while controlling for end point mean. Secondary models determined whether differences in variability between groups were associated with baseline MDD severity; antidepressant class (selective serotonin reuptake inhibitors and other related drugs; serotonin and norepinephrine reuptake inhibitors; norepinephrine-dopamine reuptake inhibitors; noradrenergic agents; or other antidepressants); and publication year.ResultsIn the 91 eligible trials (18 965 participants), variability in response did not differ significantly between antidepressants and placebo (bln σ̂, 1.02; 95% CI, 0.99-1.05; P = .19). This finding is consistent with a range of treatment effect SDs (up to 16.10), depending on the association between the antidepressant and placebo effects. Variability was not associated with baseline MDD severity or publication year. Responses to noradrenergic agents were 11% more variable than responses to selective serotonin reuptake inhibitors (bln σ̂, 1.11; 95% CI, 1.01-1.21; P = .02).Conclusions and relevanceAlthough this study cannot rule out the possibility of treatment effect heterogeneity, it does not provide empirical support for personalizing antidepressant treatment based solely on total depression scores. Future studies should explore whether individual symptom scores or biomarkers are associated with variability in response to antidepressants.

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Dataset Information

Placebo Response to Oral Administration in Osteoarthritis Clinical Trials and Its Associated Factors: A Model-Based Meta-analysis.

Importance

Objective

Data sources

Study selection

Data extraction and synthesis

Main outcomes and measures

Results

Conclusions and relevance

Publications

Placebo Response to Oral Administration in Osteoarthritis Clinical Trials and Its Associated Factors: A Model-Based Meta-analysis.

Similar Datasets

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