The placebo effect in thyroid cancer: a meta-analysis

Abstract

Context: The natural history of advanced thyroid malignancies is largely unknown. The outcome of patients included in the placebo arm of clinical trials could be reflective of their therapy-free evolution. Objective: To analyze the response rate, symptoms and adverse effects of locally advanced or metastatic differentiated (DTC) and medullary thyroid cancer (MTC) in patients treated with placebo in clinical trials. Design: PubMed (MEDLINE) and SCOPUS databases were searched through September 2015 to identify high-quality randomized controlled clinical trials. We included studies that recruited patients with DTC or MTC with a placebo arm. Methods: We conducted a meta-analysis for each category of response rate, adherence to treatment, and adverse events. An empirical Bayesian random-effect model was used. Results: We identified five clinical trials. DTC and MTC were independently analyzed. In the placebo arm, no complete response was observed; partial response occurred in 1.6% (0.6-3) and 6.4% (3.4-10.3) of DTC and MTC respectively; stable disease was described in 40.5% (34.6-46.9) and 53.9% (44.3-64.4) of DTC and MTC respectively. DTC reached a disease control rate of 42.3% (36.2-48.9) and MTC of 60.2 (50.1-71.4). Treatment discontinuation rate was 3.5% (1.9-5.5) in DTC and 5.7% (3.0-9.4) in MTC. Rate of dose reduction was 7.3% (4.8-10.5) in in MTC.Conclusions: This meta-analysis provides extensive data on the response rate and adverse effects of locally advanced or metastatic DTC and MTC in patients treated with placebo. These results may be used for comparisons with results from clinical trials without a placebo arm.

The placebo response in myasthenia gravis assessed by quantitative myasthenia gravis score: A meta‐analysis

“…Despite these limitations, we believe that this meta-analysis can be a useful contribution to the understanding of the placebo response across a variety of medical conditions and to the development of better designs for future MG trials. In the present study, we show that placebo responses in MG are quite small when assessed through QMG scores, a quantitative finding that parallels other conditions, such as cancer, 57,58 obsessive-compulsive disorder, 59,60 insomnia, 10 and hypertension. 11 These conditions differ from others such as pain, 3,[14][15][16][17][18][19][20][21]54 Parkinson's disease, 5,6,61-66 depression, 1,67 fibromyalgia, 4 epilepsy, 7 and dermatological conditions, 9 thereby emphasizing the need to map placebo responses across diseases.…”

A Review of Patient-Reported Outcomes Labeling for Oncology Drugs Approved by the FDA and the EMA (2012-2016)

“…21 Common symptoms of cancer and its treatments may be affected by placebo or nocebo effect. 22,23 Heightened expectations may also have an impact on reporting of higher order concepts such as HRQOL or QOL. For example, patients may consider new or worsening symptoms, such as vitiligo when receiving immunotherapy, to be a marker of treatment efficacy.…”

Human 3D Gastrointestinal Microtissue Barrier Function As a Predictor of Drug-Induced Diarrhea

“…For nondiarrheagenic drugs, upper limit for diarrhea incidence was set at 3% based on the rate of diarrhea in the general population, estimated at 3.2%–8.5% depending on symptom intensity (Rief et al , 2006). For diarrheagenic drugs, lower limit for diarrhea incidence was set at 40% to exclude the high background in some cancer patient placebo groups with incidence of 29.8% (95% CI of 22.9%–37.7%) (Llavero-Valero et al , 2016). Next, antibacterial agents were excluded because induction of diarrhea is secondary to disruption of commensal bacteria and subsequent Clostridium difficile colitis (Abraham and Sellin, 2012).…”