Types of studies

Randomized, controlled trials (RCTs) with placebo or active control interventions using a double‐blinded method and a parallel design.

Types of participants

Participants older than 16 years with a diagnosis of cancer, who received at least one moderately or highly emetogenic chemotherapy drug, as listed in Additional Table 1. The design of these trials was such that participants allocated to the treatment or control interventions had a good performance status.

Types of interventions

The treatment intervention will be the NK1 receptor antagonist combined with the standard antiemetic treatment, as defined elsewhere (Gralla 1999) for acute and delayed nausea and vomiting at the time when the clinical trial was conducted. The control intervention is the standard antiemetic therapy at the time the clinical trial was planned. All of these trials contemplated the use of other antiemetics to rescue participants receiving the treatment or control intervention who had breakthrough nausea and vomiting.

Types of outcome measures

• Complete control of nausea (no nausea and no use of rescue medications) in the acute (first 24 hours of treatment with chemotherapy), and delayed (after 24 hours of treatment with chemotherapy) phases of nausea and vomiting for the treatment and control interventions.

• Complete control of vomiting (no vomiting and no use of rescue medications) in acute and delayed nausea and vomiting for the treatment and control interventions.

• Adverse effects as defined by each trial that is found to be eligible for this review.

Identification of studies and data collection

Two review authors will independently screen all titles and abstracts identified in the literature search. We will also collect and tabulate the data, resolving any disagreement after discussion with a third review author. There will be no blinding to the author names, affiliated institutions, journal of publication, or study results. We plan to assess the methodological quality of each study by checking randomization and description of method of random allocation; blinding and methods to ensure appropriate masking; description of sample size; response analysis based on the intention‐to‐treat principle; and description of adverse effects, toxicity and study withdrawals. Instead of applying a quality scoring system, we plan to rate the validity of each study using a simplified rating system to assess the risk of bias (Higgins 2006).

Data collection and analysis

We will collect data on participants, methods, interventions, and the outcome measurements of interest from the original articles onto a spreadsheet. The outcome measurements will be recorded as binary data (number of participants with total control of nausea and vomiting during the study period relative to the total number of participants evaluable for treatment). If statistically appropriate, we will combine the aggregate data to obtain a pooled effect size.

Synthesis and presentation of data

We will perform a data analysis with the analysis module for RevMan 4.2.10 using the risk ratio (RR) with 95% confidence intervals (95% CI), the absolute risk reduction (ARR), the number need to treat to benefit (NNT), or the number needed to treat to harm (NNH) for five separate outcomes:

• The complete control of nausea at 24 hours of chemotherapy treatment (acute nausea).

• The complete control of nausea after 24 hours of chemotherapy treatment (delayed nausea).

• The complete control of vomiting at 24 hours of chemotherapy treatment (acute vomiting).

• The complete control of vomiting after 24 hours of chemotherapy treatment (delayed vomiting).

• The adverse event rate.

We will explore heterogeneity using Cochran Q and I² statistics, and graphical displays (funnel plots) to explore publication bias. For the sensitivity analyses we will include the comparison between random and fixed effects models, and if appropriate, stratification analysis.