Observational Study Designs for Comparative Effectiveness Research: An Alternative Approach to Close Evidence Gaps in Head-and-Neck Cancer (original) (raw)
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The Oncologist, 2013
Comparative effectiveness research (CER) can assist patients, clinicians, purchasers, and policy makers in making more informed decisions that will improve cancer care and outcomes. Despite its promise, the factors that distinguish CER from other types of evidence remain mysterious to many oncologists. One concern is whether CER studies will improve decision making in oncology or only add to the massive amount of research information that decision makers must sift through as part of their professional responsibilities. In this report, we highlight several issues that distinguish CER from the most common way evidence is generated for cancer therapy-phase I-III clinical trials. To identify the issues that are most relevant to busy decision makers, we assembled a panel of active professionals with a wide range of roles in cancer care delivery. This panel identified five themes that they considered most important for CER in oncology, as well as fundamental threats to the validity of individual CER studies-threats they termed the "kiss of death" for their applicability to practice. In discussing these concepts, we also touched upon the notion of whether cancer is special among health issues with regard to how evidence is generated and used. The Oncologist 2013;18: 760 -767 Implications for Practice: Comparative effectiveness research can inform clinical practice when studies directly compare competing therapies, include patient populations that are typical of clinical practice, and include outcomes that are meaningful to patients as well as clinicians. Busy clinicians should not waste time reading studies that are technically dense, compare outmoded treatments, have very small sample sizes, use data of questionable quality, or use dense statistical methods to address serious limitations of retrospective data. evaluating CER would differ from existing criteria for evaluating evidence. Finally, many view cancer as a unique area in health care, and this may imply that "special" principles should be applied when evaluating CER in oncology versus other medical conditions.
Relevance of randomised controlled trials in oncology
The Lancet Oncology, 2016
Well-designed randomised controlled trials (RCTs) can prevent bias in the comparison of treatments and provide a sound basis for changes in clinical practice. However, the design and reporting of many RCTs can render their results of little relevance to clinical practice. In this Personal View, we discuss the limitations of RCT data and suggest some ways to improve the clinical relevance of RCTs in the everyday management of patients with cancer. RCTs should ask questions of clinical rather than commercial interest, avoid non-validated surrogate endpoints in registration trials, and have entry criteria that allow inclusion of all patients who are fi t to receive treatment. Furthermore, RCTs should be reported with complete accounting of frequency and management of toxicities, and with strict guidelines to ensure freedom from bias. Premature reporting of results should be avoided. The bar for clinical benefi t should be raised for drug registration, which should require publication and review of mature data from RCTs, post-marketing health outcome studies, and value-based pricing.
Evaluation of the Use of Cancer Registry Data for Comparative Effectiveness Research
JAMA Network Open
IMPORTANCE Researchers often analyze cancer registry data to assess for differences in survival among cancer treatments. However, the retrospective, nonrandomized design of these analyses raises questions about study validity. OBJECTIVE To examine the extent to which comparative effectiveness analyses using observational cancer registry data produce results concordant with those of randomized clinical trials. DESIGN, SETTING, AND PARTICIPANTS In this comparative effectiveness study, a total of 141 randomized clinical trials referenced in the National Comprehensive Cancer Network Clinical Practice Guidelines for 8 common solid tumor types were identified. Data on participants within the National Cancer Database (NCDB) diagnosed between 2004 and 2014, matching the eligibility criteria of the randomized clinical trial, were obtained. The present study was conducted from August 1, 2017, to September 10, 2019. The trials included 85 118 patients, and the corresponding NCDB analyses included 1 344 536 patients. Three Cox proportional hazards regression models were used to determine hazard ratios (HRs) for overall survival, including univariable, multivariable, and propensity score-adjusted models. Multivariable and propensity score analyses controlled for potential confounders, including demographic, comorbidity, clinical, treatment, and tumor-related variables. MAIN OUTCOMES AND MEASURES The main outcome was concordance between the results of randomized clinical trials and observational cancer registry data. Hazard ratios with an NCDB analysis were considered concordant if the NDCB HR fell within the 95% CI of the randomized clinical trial HR. An NCDB analysis was considered concordant if both the NCDB and clinical trial P values for survival were nonsignificant (P Ն .05) or if they were both significant (P < .05) with survival favoring the same treatment arm in the NCDB and in the randomized clinical trial. RESULTS Analyses using the NCDB-produced HRs for survival were concordant with those of 141 randomized clinical trials in 79 univariable analyses (56%), 98 multivariable analyses (70%), and 90 propensity score models (64%). The NCDB analyses produced P values concordant with randomized clinical trials in 58 univariable analyses (41%), 65 multivariable analyses (46%), and 63 propensity score models (45%). No clinical trial characteristics were associated with concordance between NCDB analyses and randomized clinical trials, including disease site, type of clinical intervention, or severity of cancer. CONCLUSIONS AND RELEVANCE The findings of this study suggest that comparative effectiveness research using cancer registry data often produces survival outcomes discordant with those of (continued)
European Archives of Oto-Rhino-Laryngology
Purpose Randomised controlled trials (RCTs) are considered the gold standard for evaluating the efficacy of an intervention. However, previous research has shown that RCTs in several surgical specialities are poorly reported, making it difficult to ascertain if various biases have been appropriately minimised. This systematic review assesses the reporting quality of surgical head and neck cancer RCTs. Methods A literature search of PubMed and Embase was performed. Papers were included if they reported RCTs which assessed a surgical technique used to treat or diagnose head and neck cancer published during or after 2011. The CONSORT 2010 checklist was used to evaluate the reporting quality of these trials. Results 41 papers were included. The mean CONSORT score was 16.5/25 (66% adherence) and the scores ranged from 7.5 (30%) to 25. The most common omissions were full trial protocol (found in 14.6%), participant recruitment method (22%) and effect size with a precision estimate for all...
Messages from completed randomized trials in head and neck cancer
European Journal of Surgical Oncology (EJSO), 1997
During the last three decades numerous randomized trials have been conducted in head and neck squamous cell carcinoma. The issue of pre-vs post-operative radiotherapy in advanced cancers was settled in the late 70s in favour of the latter approach and new fractionation schemes are currently being investigated, with no definite answers as yet. There is no uniform policy regarding the problem of elective neck dissection in early stage anterior oral cavity carcinoma. Often some chemotherapeutic regimen is involved in clinical trials in an attempt to improve on the standard of surgery and radiotherapy. Neoadjuvant chemotherapy has never been proven to benefit patients with advanced squamous cell carcinoma of the head and neck despite being able to decrease the rate of distant metastases. Chemotherapy given prior to or simultaneously with definite radiotherapy seems to offer the best chances for preserving vital organs, such as the larynx. Methotrexate is still the least toxic and most potent drug in recurrent or metastastic disease. The chemoprotective effect of low-dose isotretinoin on multiple primaries in the head and neck has yet to be evaluated.
Validity of using cancer registry data for comparative effectiveness research
PurposeResearchers often analyze cancer registry data to assess for differences in survival among cancer treatments. However, the retrospective non-random design of these analyses raise questions about study validity. The purpose of this study was to determine the extent to which comparative effectiveness analyses using cancer registry data produces results concordant with randomized clinical trials.MethodsWe identified 141 randomized clinical trials referenced in the National Comprehensive Cancer Network Clinical Practice Guidelines for 8 common solid tumor types. For each trial we identified subjects from the National Cancer Database (NCDB) matching the eligibility criteria of the randomized trial. With each trial we used three Cox regression models to determine hazard ratios (HRs) for overall survival including univariable, multivariable, and propensity score adjusted models. Multivariable and propensity score analyses controlled for potential confounders including demographic, c...