Approach for ergonomic assessment of self-propelled combine harvester seats based on anthropometric body dimensions.

Objectives. The seat dimensions of self-propelled combine harvesters are designed without consideration of body dimensions of the user population and vary with make and models of combines. Methods. This research proposes a method to determine the percentage of seat match, upper mismatch and lower mismatch using the anthropometric body dimensions of Indian harvester operators. The seat dimensions of five popular combine harvester makes were measured and compared to the body dimensions of the operators. Results. The selected seats had 100, 44-70, 81-96, 98-100, 63-83, 59-94 and 55-97% mismatch for seat height, seat length, seat pan breadth, seat backrest height, upper backrest breadth, lower backrest breadth and steering wheel clearance, respectively. These data were used to recommend seat dimensions for combine harvesters. Seat height, seat length, seat pan breadth, seat backrest height, upper backrest breadth, lower backrest breadth and steering wheel clearance are recommended as 399, 362, 456, 400, 243, 386 and 190 mm, respectively. Conclusions. The recommended seat dimensions matched the user population anthropometric dimensions 94-100%. This approach will help to assess seat dimensions based on anthropometric data for a comfortable posture to prevent health risks such as musculoskeletal disorders (MSDs) among operators.

An adaptive population enrichment phase III trial of TRC105 and pazopanib versus pazopanib alone in patients with advanced angiosarcoma (TAPPAS trial).

Background: Major challenges in clinical trials of ultra-orphan oncology diseases include limited patient availability and paucity of reliable prior data for estimating the treatment effect and, therefore, determining optimal sample size. Angiosarcoma (AS), a particularly aggressive form of soft tissue sarcoma with an incidence of about 2000 cases per year in the United States and Europe is poorly addressed by current systemic therapies. Pazopanib, an inhibitor of vascular endothelial growth factor receptor (VEGFR) is approved for the treatment of AS, with modest benefit. TRC105 (carotuximab) is a monoclonal antibody to endoglin, an essential angiogenic target highly expressed on proliferating endothelium and both tumor vessels and tumor cells in AS, that has the potential to complement VEGFR tyrosine kinase inhibitors. In a phase I/II study of soft tissue sarcoma, TRC105 combined safely with pazopanib and the combination demonstrated durable complete responses and encouraging progression-free survival (PFS). In addition, there was a suggestion of superior benefit in patients with cutaneous lesions versus those with the non-cutaneous lesions. Patients and methods: This article describes the design of a recently initiated phase III trial of TRC105 And Pazopanib versus Pazopanib alone in patients with advanced AngioSarcoma (TAPPAS trial). Given the ultra-orphan status of the disease and the paucity of reliable prior data on PFS or overall survival (end points required for regulatory approval as a pivotal trial), an adaptive design incorporating population enrichment and sample size re-estimation was implemented. The design incorporated regulatory input from the Food and Drug Administration (FDA) and European Medicines Agency and proceeded following special protocol assessment designation by the FDA. Conclusions: It is shown that the benefit of the adaptive design as compared with a conventional single-look design arises from the learning and subsequent improvements in power that occur after an unblinded analysis of interim data. Registered on Clinicaltrials.gov: NCT02979899.

A proposal for integrated efficacy-to-effectiveness (E2E) clinical trials.

We propose an "efficacy-to-effectiveness" (E2E) clinical trial design, in which an effectiveness trial would commence seamlessly upon completion of the efficacy trial. Efficacy trials use inclusion/exclusion criteria to produce relatively homogeneous samples of participants with the target condition, conducted in settings that foster adherence to rigorous clinical protocols. Effectiveness trials use inclusion/exclusion criteria that generate heterogeneous samples that are more similar to the general patient spectrum, conducted in more varied settings, with protocols that approximate typical clinical care. In E2E trials, results from the efficacy trial component would be used to design the effectiveness trial component, to confirm and/or discern associations between clinical characteristics and treatment effects in typical care, and potentially to test new hypotheses. An E2E approach may improve the evidentiary basis for selecting treatments, expand understanding of the effectiveness of treatments in subgroups with particular clinical features, and foster incorporation of effectiveness information into regulatory processes.

Tractor controls actuating force limits for Indian operators.

In four-wheel tractors, proper design of controls is important for comfortable and safe operation of the tractor. The design involves location and dimensions of controls as well as strength limits for operating these controls. The present study was aimed to quantify human strength for operation of tractor controls and to recommend the maximum control actuating forces for normal operation of tractors based on strength capability of 3,423 Indian male agricultural workers. The 5th percentile values of strength parameters i.e. leg strength sitting (left and right), foot strength sitting (right), torque strength (both hands) sitting, push strength (left hand and right hand) sitting and pull strength (left hand and right hand) sitting of agricultural workers collected using a strength measurement set-up were taken into consideration for the study. It was recommended that the maximum actuating forces for normal operation of frequently operated brake and clutch pedals of tractors should not exceed 260 N and 125 N based on 5th percentile values of right and left leg strength of male agricultural workers, respectively. The maximum actuating force required in steering wheel operation should not exceed 51 N based on 5th percentile value of torque strength (both hands) sitting of workers. The maximum actuating forces required for operating frequently operated levers viz. gear selection, speed selection, hydraulic control and hand throttle of Indian tractors should not exceed 46 N, 46 N, 25 N and 25 N, respectively. It may be concluded that the maximum actuating force limits as given in Bureau of Indian Standards IS 10703 are very high as compared to the findings of the study based on strength data of Indian male operators, which highlight the need to revise the standard.

Ride vibration on tractor-implement system.

India is the largest manufacturer of tractors in the world. They are used for primary and secondary tillage operations and as a means of transportation. Vibration in tractor driving can cause deafness and disorders of the spinal column and stomach. The effect of implements on tractor ride is not well understood in India. The present study was undertaken to quantify ride vibration of a low horsepower tractor-implement system. Tractor ride vibration levels have been measured at the person-seat interface along three mutually perpendicular axes, longitudinal, lateral and vertical, under different operating conditions. It was observed that the acceleration levels increased as forward speed of travel increased under most of the operating conditions. There was no conclusive difference in measured acceleration levels on a tar-macadam road and a farm road during transport mode. The measured ride vibration levels under different operating conditions were evaluated as per ISO 2631/1 (1985), Geneva, and BS 6841 (1987), London, standards. On the basis of this study, it is concluded that the exposure time for the tractor operator should not exceed 2.5 h during ploughing and harrowing operations. Increasing exposure time may cause severe discomfort, pain and injury.

Efficiency robust tests of independence in contingency tables with ordered classifications.

Ordered categorical data occur frequently in biomedical research. The linear by linear association test for ordered R x C tables permits the investigator to specify row and column scores for analysis. When an investigator believes that there may be more than one set of reasonable scores or when more than one investigator proposes scores, we need a method to decide upon a single procedure to use. We show how to use efficiency robustness principles to combine tests from two or more sets of scores into one robust test for analysis. This test minimizes the worst possible efficiency loss over all the sets of scores. We illustrate the methodology for the R x C case and, in detail, for the important special 2 x C case.

Exact logistic regression: theory and examples.

We provide an alternative to the maximum likelihood method for making inferences about the parameters of the logistic regression model. The method is based appropriate permutational distributions of sufficient statistics. It is useful for analysing small or unbalanced binary data with covariates. It also applies to small-sample clustered binary data. We illustrate the method by analysing several biomedical data sets.

Exact permutational tests for group sequential clinical trials.

An efficient numerical algorithm is developed for computing stopping boundaries for group sequential clinical trials. Patients arrive in sequence, and are randomized to one of two treatments. The data are monitored at interim time points, with a fresh block of patients entering the study from one monitoring point to the next. The stopping boundaries are derived from the exact joint permutational distribution of the linear rank statistics observed across all the monitoring times. Specifically, the algorithm yields the exact boundary generating function, Pr(W1 < b1, W2 < b2, ..., Wi-1 < bi-1, Wi = wi), where Wj is the linear rank statistic at the jth interim time point. The distribution theory is based on assigning ranks after pooling all the patients who have entered the study, and then permuting the patients to the two treatments independently within each block of newly arrived patients. The methods are applicable for an arbitrary number of monitoring times, which need not be specified at the start of the study. The data may be continuous or categorical, and censored or uncensored. The randomization rule for treatment allocation can be adaptive. The algorithm is especially useful during the early stages of a clinical trial, when very little data have been gathered, and stopping boundaries are based on the extreme tails of the relevant boundary generating function. In that case the corresponding large-sample theory is not very reliable. To illustrate the techniques we present a group sequential analysis of a recently completed study by the Eastern Cooperative Oncology Group.

The exact analysis of contingency tables in medical research.

A unified view of exact nonparametric inference, with special emphasis on data in the form of contingency tables, is presented. While the concept of exact tests has been in existence since the early work of RA Fisher, the computational complexity involved in actually executing such tests precluded their use until fairly recently. Modern algorithmic advances, combined with the easy availability of inexpensive computing power, has renewed interest in exact methods of inference, especially because they remain valid in the face of small, sparse, imbalanced, or heavily tied data. After defining exact p-values in terms of the permutation principle, we reference algorithms for computing them. Several data sets are then analysed by both exact and asymptotic methods. We end with a discussion of the available software.

Power and sample size calculations for exact conditional tests with ordered categorical data.

We develop an algorithm for computing sample sizes, equal or unequal, for categorical data. We illustrate its use in the two-sample setting using the Wilcoxon rank-sum statistic, but the algorithm accommodates the entire class of linear rank statistics and can be extended to include nonlinear rank statistics as well. The sample size determinations can be based on either exact power or on a very precise Monte Carlo estimate of it. To reduce the computations further, power can be computed as a function of asymptotic critical values when the number of categories is not too small. For the Wilcoxon statistic we show that this approximation works well if there are more than five response categories.

Exact inference for matched case-control studies.

In an epidemiological study with a small sample size or a sparse data structure, the use of an asymptotic method of analysis may not be appropriate. In this paper we present an alternative method of analyzing data for case-control studies with a matched design that does not rely on large-sample assumptions. A recursive algorithm to compute the exact distribution of the conditional sufficient statistics of the parameters of the logistic model for such a design is given. This distribution can be used to perform exact inference on model parameters, the methodology of which is outlined. To illustrate the exact method, and compare it with the conventional asymptotic method, analyses of data from two case-control studies are also presented.

Anxiety levels in patients randomized to adjuvant therapy versus observation for early breast cancer.

We studied anxiety levels in 68 patients who had been randomized to adjuvant chemotherapy v observation on two Eastern Cooperative Oncology Group (ECOG) protocols. All subjects were women who had undergone total or modified radical mastectomy for breast cancer. Immediately before breast protocol randomization and again 3, 6, and 12 months later, patients completed two self-report measures: the State-Trait Anxiety Inventory and the SCL-90. There were no consistent trends in anxiety levels over time. At each test point, patients under observation displayed higher anxiety scores than did patients receiving adjuvant therapy, but these differences failed to attain statistical significance. Power calculations indicate that these results rule out the possibility of major differences in anxiety levels among patients randomized to observation v adjuvant therapy, but a larger patient sample is required before a definitive statement can be made about smaller differences.

An intervention study of tobacco chewing and smoking habits for primary prevention of oral cancer among 12,212 Indian villagers.

In a house-to-house screening survey, 12,212 tobacco chewers and smokers were selected from the rural population in the Ernakulam district, Kerala state, India. These individuals were interviewed for their tobacco habits and examined for the presence of oral cancer and precancerous lesions, first in a baseline survey, and then annually, over a five-year period. They were educated using personal and mass media communication to give up their tobacco habits. The control group was provided from the results of the first five years of a 10-year follow-up study conducted earlier by the authors in the same area with the same methodology but on different individuals without any educational intervention. The stoppage of the tobacco habit was substantially higher in the intervention group (9.4%) compared to the control group (3.2%). A logistic regression analysis showed that the behavioural intervention was helpful to all categories of individuals, however, the effect was different for different categories: intervention was more helpful to men, chewers, and those with a long duration of the habit. These individuals rarely quit their habit without intervention.

Exact confidence intervals following a group sequential test.

A numerical method is used to compute confidence intervals, which have exact coverage probabilities, for the mean of a normal distribution following a group sequential test. This method, which uses an ordering of the sample space similar to that employed by Siegmund (1978, Biometrika 65, 341-349), is contrasted with the usual confidence interval for the mean.

Exact significance testing to establish treatment equivalence with ordered categorical data.

This communication concerns the problem of establishing the therapeutic equivalence of two treatments that are being compared on the basis of ordered categorical data. The problem is formulated as a significance test in which the null hypothesis specifies a treatment difference. An efficient numerical algorithm for computing the exact significance level is provided, along with a simple method for obtaining the asymptotic significance level. Both methods are applied to a clinical trial of a new agent versus an active control. Guidelines for when to use the exact procedure and when to rely on asymptotic theory are provided.

Charts for the early stopping of pilot studies.

Cooperative oncology groups usually run pilot studies of new agents or combinations concurrently with their major randomized clinical trials. A primary objective of these studies is to determine whether the new regimen should be tested further in a group-wide clinical trial. The accrual goals of such pilot studies are typically fixed in advance at between 30 and 40 patients, on the grounds that this number provides a reasonably tight confidence interval on the true response rate. Nevertheless early termination of pilot studies is often desirable either because the regimen appears inactive or because early results indicate extreme activity and justify immediate testing in a randomized study. Statistical charts are provided for early termination in both these situations. The charts are read by specifying the number of evaluable patients already accrued, the number of responses observed and the minimum true response rate, theta 0, at which the regimen would be considered active. The charts provide the posterior probability that the true response rate exceeds theta 0, that is, that the regimen is active. An additional chart that computes a 90% probability interval for the true response rate, based on the observed rate and sample size, is also provided. The use of the chart is illustrated with two examples from the Eastern Cooperative Oncology Group.

Chemotherapy for metastatic non-small cell bronchogenic carcinoma: EST 2575, generation III, HAM versus CAMP.

Between September 1978 and March 1979 the Eastern Cooperative Oncology Group compared the CAMP (cyclophosphamide, doxorubicin, methotrexate, and procarbazine) and HAM (hexamethylmelamine, doxorubicin, and methotrexate) regimens in 154 patients with metastatic non-small cell bronchogenic carcinoma. Most patients were ambulatory (77%) and had not received prior radiotherapy (59%). HAM produced two complete responses (CR) and eight partial responses (PR) (n = 77; 2.5% CR, 10.4% PR, 13% overall response) whereas CAMP resulted in five CR and 12 PR (n = 77; 6.5% CR, 15.6% PR, 22% overall response). This difference was not statistically significant (P = 0.14 with Fisher's exact 2-sided test) nor was the difference in overall median survival (HAM, 22.1 weeks and CAMP, 19.3 weeks). Responders had a significantly improved median survival (32.5 weeks) compared to nonresponders (17.9 weeks, P = 0.018). Ambulatory performance status and lack of prior radiotherapy were positive predictors for prolonged survival.

Chemotherapy for inoperable, non-small cell bronchogenic carcinoma: EST 2575, generation II.

Between 1976 and 1978 the Eastern Cooperative Oncology Group tested ten regimens in 415 patients with histologically documented, inoperable non-small cell bronchogenic carcinoma. Most patients were ambulatory (69%) and had extensive disease (69%). Patients were stratified by cell type: squamous cell carcinoma (SQ), large cell anaplastic carcinoma (LC), or adenocarcinoma (AD). Ineffective single agents (including cell types tested and percent complete and partial responses) were dactinomycin (SQ, 6%), dianhydrogalactitol (SQ, 0), ftorafur (AD and LC, 3%), and piperazinedione (AD and LC, 7%), Ineffective combination regimens included the contemporary standard regimen cyclophosphamide (CYT) plus CCNU (SQ, AD, and LC, 9%), methotrexate plus doxorubicin (ADR) plus CYT plus CCNU (MAC) (SQ and AD, 12%), and mitolactol plus ADR (AD and LC, 8%). When compared to CYT plus CCNU the following regimens demonstrated significant activity: CYT plus bleomycin plus cisplatin (SQ, 23%; P = 0.02) and ADR plus 5-FU plus cisplatin (AD and LC, 24%; P = 0.006). Mitomycin demonstrated marginal activity in squamous cell cancer (19%, P = 0.06). Neither "active" regimen improved survival although responders to any regimen had a significant prolongation of median survival (31.6 vs 15.7 weeks, P = 0.002). The MACC regimen, piperazinedione, and mitomycin were substantially more toxic than the two effective regimens, which were adequately tolerated. Ambulatory performance status, limited disease, and prior surgery were significant positive prognostic variables whereas prior radiation and pretreatment weight loss adversely affected response or survival.