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R J Simes

Publications and source records attributed to R J Simes.

At least 19 recordsLinked to original sources
PubMed1992

Quality of life in clinical trials of adjuvant therapies. International Breast Cancer Study Group (formerly Ludwig Group).

Clinical trials of adjuvant therapies usually measure the effectiveness of treatments by comparing disease-free survival or overall survival. These take into consideration only indirectly the quality of life experienced by the patients. We present some approaches that were developed to assess the impact of adjuvant therapy on the quality of life of breast cancer patients, as well as new methods created to compare treatments based on time spent without symptoms and toxicity (TWiST). The integration of these two methods (measuring quality and comparing duration of time) will provide a new tool for evaluating benefits from treatments given in the adjuvant setting.

Antineoplastic Agents↗
PubMed1990

Quality adjusted survival analysis.

We present a technique, quality adjusted survival analysis, for the analysis of controlled trials where patients may experience several health states which differ in their quality of life. When the data are censored, a survival analysis of the quality adjusted life years achieved may involve informative censoring, and produce biased estimates. To overcome this, we partition the survival curve; the resulting areas, which represent the mean time in each state, are multiplied by utility weights to provide an unbiased estimate of (restricted) quality adjusted survival. If the appropriate weights are in doubt, the results are best presented as a threshold analysis over the utility weights, allowing individual recommendation to be read from a simple graph. The certainty of the conclusions can be presented as confidence bands on the threshold line. The techniques are illustrated with a re-analysis of a large three-arm trial of adjuvant chemoendocrine therapy for stage II breast cancer in postmenopausal women. This shows that if the value of time spent in toxicity is greater than the time spent in relapse, we can be 95 per cent confident that chemoendocrine therapy is the preferred option.

Breast Neoplasms↗
PubMed1989

Costs and benefits of adjuvant therapy in breast cancer: a quality-adjusted survival analysis.

The use of adjuvant chemotherapy for postmenopausal patients with early breast cancer remains controversial because the potential benefits in terms of prolongation of disease-free survival (DFS) and overall survival (OS) must be balanced against the toxicity of treatment. Following mastectomy, 463 evaluable postmenopausal women with node-positive breast cancer were randomized to receive either chemoendocrine therapy for 1 year, or endocrine therapy alone for 1 year, or no adjuvant therapy (Ludwig Trial III). At 7-years median follow-up, OS was longer for the chemoendocrine-treated patients compared with controls (P = .04) and compared with the adjuvant endocrine therapy-alone group (P = .08). In order to balance this therapeutic advantage against the toxic effects of treatment, OS time was divided into time with toxicity (TOX), time without symptoms and toxicity (TWiST), and time after systemic relapse (REL). TOX and REL were weighted by coefficients of utility relative to TWiST and the results added to give a period of quality-adjusted survival (Q-TWiST). Benefits measured by Q-TWiST generally favored chemoendocrine therapy. For example, if TOX and REL were both given utility coefficients of 0.5 relative to 1.0 for TWiST, then by 7 years the average Q-TWiST for chemoendocrine therapy was 6.7 months longer than for no-adjuvant therapy (P = .05) and 4.1 months longer than for endocrine therapy alone (P = .20). Quality-adjusted survival analysis is recommended in assessing costs and benefits of toxic adjuvant therapy. In this example, it supports the use of chemoendocrine therapy in postmenopausal node-positive patients for a wide range of relative values assigned to periods with symptoms and toxicity.

Antineoplastic Agents↗
PubMed1987

Patient treatment preference in advanced breast cancer: a randomized cross-over study of doxorubicin and mitozantrone.

Twenty-two patients with advanced breast cancer participated in a randomized cross-over study of one cycle each of doxorubicin followed 3 weeks later by mitozantrone or vice versa. Before further treatment, patients selected which drug they wished to continue. Of 18 patients completing the study, 13 chose to continue mitozantrone, 2 doxorubicin and 3 had no preference (P = 0.007). Patients were told to assume similar efficacy of the two drugs and drug preference was based primarily on side-effects. Patient self-assessment of quality of life and physician assigned toxicity scores both indicated that nausea and vomiting, appetite and alopecia were significantly worse following doxorubicin than after mitozantrone. Except for alopecia, no significant period or carry-over effects were noted although the power of the study to detect such interactions was low. This study design may prove useful in enabling patients to select their preference between two treatments of similar efficacy.

Adult↗
PubMed1986

Informed consent.

Explore the source record for details and available documents.

Attitude↗
PubMed1986

Randomised comparison of procedures for obtaining informed consent in clinical trials of treatment for cancer.

Methods of obtaining informed consent have evolved differently in Western countries without substantive information on the impact of these different practices on the patients. A randomised study was performed to compare two commonly adopted methods of seeking consent to randomised treatment: an individual approach at the discretion of each doctor and a uniform policy of total disclosure of all relevant information. The impact of both consent procedures on the patient's understanding and anxiety levels and on the doctor-patient relationship was assessed by means of a questionnaire given soon after the consent interview. Fifty seven patients were assigned at random to two groups: to 29 patients an individual approach to seeking consent was adopted and to 28 patients all relevant information was given. Seven patients refused consent to randomised treatment, with slightly more refusals by patients in the total disclosure group (5 v 2, p = 0.25). The main effects of total disclosure of all information compared with an individual approach to seeking consent were: a better understanding of treatment and side effects and of research aspects of the treatments; less willingness to agree to randomised treatment; and increased anxiety. No significant differences were found in patients' perceptions of the doctor-patient relationship. A repeat questionnaire given three to four weeks later no longer showed significant differences between the two groups.

Anxiety↗
PubMed1986

Publication bias: the case for an international registry of clinical trials.

A problem in evaluating different therapies from a review of clinical trials is that the published clinical trial literature may be biased in favor of positive or promising results. In this report, a model is proposed for reviewing clinical trial results which is free from publication bias based on the selection of trials registered in advance in a registry. The value of a registry is illustrated by comparing a review of published clinical trials located by a literature search with a review of registered trials contained in a cancer trials registry. Two therapeutic questions are examined: the survival impact of initial alkylating agent (AA) v combination chemotherapy (CC) in advanced ovarian cancer, and the survival impact of AA/prednisone v CC in multiple myeloma. In advanced ovarian cancer, a pooled analysis of published clinical trials demonstrates a significant survival advantage for combination chemotherapy (median survival ratio of CC to AA, 1.16; P = .02). However, no significant difference in survival is demonstrated based on a pooled analysis of registered trials (median survival ratio, 1.05; P = .25). For multiple myeloma, a pooled analysis of published trials also demonstrates a significant survival advantage for CC (median survival ratio, 1.26; P = 04), especially for poor risk patients (ratio, 1.66; P = .002). A pooled analysis of registered trials also shows a survival benefit for patients receiving combination chemotherapy (all patients, P = .06; poor risk, P = .03), but the estimated magnitude of the benefit is reduced (all patients: ratio, 1.11; poor risk: ratio, 1.22). These examples illustrate an approach to reviewing the clinical trial literature, which is free from publication bias, and demonstrate the value and importance of an international registry of all clinical trials.

Alkylating Agents↗
PubMed1985

Treatment selection for cancer patients: application of statistical decision theory to the treatment of advanced ovarian cancer.

Optimal treatment selection for patients with chronic disease, especially advanced cancer, requires careful consideration in weighing risks and benefits of each therapy. The application of statistical decision theory to such problems provides an explicit and systematic means of combining information on risks and benefits with individual patient preferences on quality-of-life issues. This paper evaluates the strengths and weaknesses of this methodology by using, as an example, treatment selection in advanced ovarian cancer. Possible treatment options and the major consequences of each are first outlined on a decision tree. The probability of various outcomes is estimated from the literature and methods for assessing the relative value or utility of each outcome are illustrated by interviews with 9 volunteers. Based on decision analysis, the recommended treatment for advanced ovarian cancer is found to be highly dependent on survival estimates but far less dependent on other probability estimates or the method of obtaining utilities. Individual preferences are also found to influence the treatment choice. The analysis illustrates that an important strength in using decision theory is its ability to identify key factors in the decision through sensitivity analysis. This may help both the physician selecting treatment and the investigator planning clinical trials which compare these therapies. In addition, this method can help in planning a trial's sample size by determining what survival difference between therapeutic strategies is worth detecting. Some problems identified with this methodology include the need for several simplifying assumptions and the difficulties in assessing individual preferences. On balance, we believe decision theory in this setting can play a useful role in complementing the physician's clinical judgement.

Alkylating Agents↗
PubMed1985

Exploratory data analysis and the use of the hazard function for interpreting survival data: an investigator's primer.

This report discusses how one can use the hazard function to gain important insights on the patterns of failure in clinical studies when the principal endpoint is a time metric. These new insights may help gain increased understanding into the pathogenesis of a chronic disease and how it is affected by treatment intervention. The qualitative behavior of the hazard function can reveal whether mortality is increasing, decreasing, or is constant over time. Simple graphic plots are all that is necessary to show characteristic failure patterns. These informal procedures are in the spirit of carrying out exploratory analyses on the data. This report discusses the organization of clinical data using a "branch and leaf" plot, outlines the calculation of the hazard function and life table, and uses examples from lung cancer and uveal melanoma to illustrate calculations and ways of interpreting hazard functions.

Adenocarcinoma↗
PubMed1985

Risk-benefit relationships in cancer clinical trials: the ECOG experience in non-small-cell lung cancer.

Although there is widespread recognition of the need to critically evaluate risks and benefits for patients participating in clinical trials, the actual implementation can be a difficult task. As an illustration of the analytic difficulties, we reviewed the experience of the Eastern Cooperative Oncology Group (ECOG) in advanced (inoperable) non-small-cell lung cancer over the past ten years (1973 to 1983). Of 2,714 ECOG patients analyzed, 15% showed objective tumor response. Median survival of all patients was 4.2 months, with approximately one half of patient's survival spent on protocol treatment. Thirty-nine percent of patients experienced at least one episode of severe or worse toxicity from therapy. Chemotherapy impact on this disease was assessed by examining trends in patient outcomes over the decade studied and by comparisons with patients receiving no treatment from earlier Veterans Administration Lung Protocols. Introducing more intensive chemotherapy regimens over this period appears to have resulted in some improvement in survival and response to therapy, but at the expense of greater toxicity. Despite modest survival gains achieved by these evolving trials, the community benefit from such trials seems clear, both in identifying ineffective therapies (and avoiding their general use) and as an important step in developing effective regimens. However, the decision for an individual patient to participate in a trial may involve difficult trade-offs between risk and benefit. This study suggests the need to identify subgroups of patients unlikely to benefit from trial participation and stresses the importance of incorporating patient preferences in the final decision. Some of the problems in patient communication are discussed.

Adenocarcinoma↗
PubMed1979

Activity of mouse macrophages purified by adherence to, and removal from, a plastic surface.

Mouse peritoneal exudate macrophages were allowed to adhere to plastic Petri dishes and, after washing, were removed by means of EDTA. Cells with the morphology of macrophages were recovered in a fair degree of purity (90-98%) but in low yield (31-34%). The macrophages recovered were fully active in the following ways: re-adherence to glass; pinocytosis of colloidal gold; phagocytosis of opsonized sheep erythrocytes; binding cytophilic antibody; production of lymphocyte activating factor; cytotoxic and cytostatic effects on tumour cells.

Animals↗
PubMed1975

Ultrastructure of an odontogenic myxoma.

The ultrastructural findings in a case of odontogenic myxoma are described. The main cell type was characterized by several cytoplasmic processes, intracytoplasmic fibrils, numerous glycogen particles, and salient Golgi complexes. A few mitochondria and a scarce endoplasmic reticulum was noted. The matrix consisted of numerous granules with fibrillar projections, collagen bundles, and smaller fibers. The over-all ultrastructural features of this tumor were similar to those described in the human cardiac myxoma and in Wharton's jelly and could be clearly differentiated from the fine structural characteristics of other connective tissue tumors.

Adult↗
PubMed1975

Role of a non-committed accessory cell in the in vivo suppression of a syngeneic tumour by immune lymphocytes.

CBA/J mice bearing a methylcholanthrene-induced sarcoma exhibited concomitant immunity to the tumour. The cellular basis for this immunity was investigated by local transfer of mixtures of lymphoid and tumour cells into the footpads of syngeneic mice. Peritoneal exudate cells obtained from tumour-bearing mice 1 day after intraperitoneal injection of saline had a marked tumour-suppressive effect, whereas normally resident peritoneal cells did not. Peritoneal exudate cells from which adherent cells had been removed ('lymphocytes') had a suppressive effect at high or low lymphocyte: tumour cell ratios in normal recipients. In irradiated (450 R) recipients the lymphocytes were suppressive at high ratios only. At low ratios the lymphocytes were suppressive only if the irradiated recipients had been partially shielded or if the lymphocytes were admixed with peritoneal exudate cells from normal mice. It is concluded that an amplifying mechanism, possibly involving macrophages, can operate in tumour cell suppression initiated by immune lymphocytes.

Animals↗