Technology Assessment: Report on the Relative Efficacy of Oral Cancer Therapy for Medicare Beneficiaries Versus Currently Covered Therapy, Part 1. Gefitinib and Erlotinib for Non-Small Cell Lung Cancer (continued)

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Report on the Relative Efficacy of Oral Cancer Therapy for Medicare Beneficiaries Versus Currently Covered Therapy

Part 1. Gefitinib and Erlotinib for Non-Small Cell Lung Cancer (continued)

Methods

Search Strategy

The search strategy was constructed by combining three concepts:

The intervention gefitinib or erlotinib.
Non-small cell lung cancer.
Prospective clinical trials.

To identify the intervention concept, since these new drugs lack a specific term in the MeSH® lexicon, we used text word searching for the following test strings: gefitinib or erlotinib or Iressa or Tarceva or lapatinib or ekb-569 or ci-1033 or zd1839 or osi-774. The lung cancer concept was implemented using the MeSH terms lung neoplasms (exploded) or carcinoma, non-small-cell lung (combined with a Boolean "or"). A published strategy, validated for finding randomized controlled trials (RCTs), was used to identify prospective clinical trials.⁴ This strategy is designed to find all prospective clinical trials (maximize sensitivity), rather than to eliminate non-randomized trials (maximize specificity), and so is appropriate for this study's goal of finding phase II and III prospective clinical trials. Finally, the three concepts were combined (Boolean "or"). The strategy was executed in MEDLINE® (1966 through September 2004, updated February and August 2005) and limited to articles published in the English language. The exact text of the OVID MEDLINE® versions of the search strategy is provided in Appendix A.

Supplemental searches were conducted in International Pharmaceutical Abstracts and The Cochrane Library (CENTRAL Register of Controlled Clinical Trials and Health Technology Assessment database) and in the American Society of Clinical Oncology 2004 and 2005 annual meeting abstracts databases. Reference lists of identified studies and relevant systematic reviews and meta-analyses were hand-checked. Additional articles not indexed in the major bibliographies by August 2005 were identified through ongoing searches and discussions with field experts and monitoring new sources.

Selection Criteria

Each citation identified from the search strategies was evaluated according to the following selection criteria. Evaluations were performed by the authors.

Inclusion criteria:
Patients	Patients with locally advanced or metastatic non-small cell lung cancer who have not received chemotherapy or who have failed to respond to platinum-based chemotherapy
Interventions	Gefitinib (Iressa™ [ZD1839]) or Erlotinib (Tarceva™ [OSI-774]) or CI-1033 or Lapatinib (GW572016) or EKB-569
Comparators	Platinum-based chemotherapy regimens or docetaxel plus supportive care or best supportive care alone

Study designs:

For efficacy questions: Prospective clinical trials; may be phase II uncontrolled, or phase III randomized controlled trials.
For studies of adverse effects: May be retrospective or prospective case series, cohort studies, or clinical trials provided the number of patients treated (at risk for adverse effects) as well as the number with adverse effects can be ascertained.
For studies of predictors of response: May be retrospective or prospective case series, cohort studies, case-control studies, or clinical trials provided the response can be ascertained for patients with and without the predictor.

Outcomes:

For efficacy questions: Survival, disease-free survival, response rates, and quality of life.
For studies of adverse effects: Adverse effects, tolerability, and compliance with treatment.
For studies of predictors of response: Predictive value of patient or tumor characteristics that are associated with clinically important differences in treatment response that are:
- Related to the mechanism of action of the drug (i.e., molecular target).
- Candidates for diagnostic testing (even if not commercially or clinically available currently [e.g., Polymerase Chain Reaction]).

Data Abstraction

The following data were abstracted from included studies: study design, population characteristics (including gender, age, and diagnosis), eligibility and exclusion criteria, interventions (dose and duration), outcomes assessed and results for each outcome.

We developed data collection forms in Excel® (Microsoft®; Redmond, WA) and summarized the data in evidence tables formatted like those in a 2003 report from the UK National Institute on Clinical Excellence (NICE).⁵

Quality Assessment

We assessed the quality of included studies by evaluating elements of internal validity (e.g., randomization and allocation concealment; similarity of compared groups at baseline; specification of eligibility criteria; blinding of assessors, care providers, and patients), and external validity (e.g., description of the patient population; similarity to the target population of the report; use of highly selective criteria).

We used as a framework the quality assessment criteria from NICE.⁵ These are displayed in Appendix B. They provide specific criteria for the range of study designs used in this report including experimental studies, cohort studies, case-control studies, and case series.

Data Synthesis

In addition to a narrative description of study findings, data were reanalyzed in order to determine statistics in a common metric and display data comparatively. In particular, we recalculated measures of association between predictors and response where univariate raw data were available in order to calculate odds ratios and 95 percent confidence intervals. Such calculations were performed using Comprehensive Meta Analysis, version 2.2.023 (Biostat: Englewood, NJ).

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