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The utility of the International Working Group (IWG) 2006 response criteria for myelodysplastic syndromes (MDS) as a surrogate endpoint for outcomes is unclear. We assessed the validity of the IWG 2006 response criteria in a large cohort of higher‐risk MDS patients (pts) treated at centers from the MDS Clinical Research Consortium. The best overall response rate (ORR) by IWG 2006 criteria to first‐line therapy among 597 evaluable pts was 38% and include complete response (CR) 16%, marrow CR (mCR) 2%, partial response (PR) 10%, hematological improvement (HI) 10%, stable disease (SD) 33%, and progressive disease (PD) 24%. CR was associated with a better overall survival (OS) compared to all other response groups (P, In higher risk MDS patients responses associated with restoration of effective hematopoiesis namely complete remission (CR) are associated with better outcomes.Marrow CR without hematological improvement outside context of allogeneic hematopoietic stem cell transplant should not be included in response criteria assessing new therapeutic agents in MDS.

Standardized guidelines for assessing tumor response to therapy are essential for designing and conducting clinical trials. The Response Evaluation Criteria In Solid Tumors (RECIST) provide radiological standards for assessment of solid tumors. However, no such guidelines exist for the evaluation of intraocular cancer, and ocular oncology clinical trials have largely relied on indirect measures of therapeutic response-such as progression-free survival-to evaluate the efficacy of treatment agents. Herein, we propose specific criteria for evaluating treatment response of retinoblastoma, the most common pediatric intraocular cancer, and emphasize a multimodal imaging approach for comprehensive assessment of retinoblastoma tumors in clinical trials.

BACKGROUND The 1993 International Neuroblastoma Response Criteria (INRC) were revised in 2017 to include modern functional imaging studies and methods for quantifying disease in bone marrow. We hypothesized the 2017 INRC would enable more precise assessment of response to treatment and provide superior prognostic information compared with the 1993 criteria. METHODS High-risk (HR) neuroblastoma patients from two institutions in Chicago diagnosed between 2006 and 2016 were identified. Patients were assessed post induction chemotherapy via the 1993 and 2017 INRC and classified as responder (≥ mixed response [MXR] or ≥ minor response [MR], respectively) or nonresponder (

Hepatic involvement in Hodgkin lymphoma (HL) is uncommon (∼5% of patients) but always implies stage IV disease. Accurate staging is mandatory for making the appropriate risk assignment and treatment decisions. The Staging Evaluation and Response Criteria Harmonization for Childhood, Adolescent and Young Adult Hodgkin Lymphoma (SEARCH for CAYAHL) international working group conducted a systematic literature review of liver involvement in HL patients with the aim to propose a universally acceptable definition for liver involvement in pediatric HL. Thirty-three articles describing 6985 pediatric and adult HL patients were reviewed, of which 539 (7.7%) mentioned liver involvement. The literature did not provide a uniform definition of hepatic involvement and we propose consensus criteria derived from the EuroNet and Children's Oncology Group protocols, where liver involvement is defined as any hepatic lesion on computed tomography scan that correlates with 18 F-FDG uptake greater than background liver. A clear definition of liver lesions is necessary to consistently identify liver involvement and compare its impact on outcomes among protocols worldwide.

The prognosis of central nervous system (CNS) relapse of systemic non-Hodgkin lymphoma is poor with 1-year survival historically at 0% to 20%. Aiming to improve these results, we performed a multicenter phase 2 study in patients with a CNS relapse, with or without concurrent systemic relapse. Treatment consisted of 2 cycles of R-DHAP alternating with high-dose methotrexate (MTX) and was combined with intrathecal rituximab. Responding patients received a third R-DHAP-MTX cycle followed by busulfan and cyclophosphamide myeloablative therapy and autologous stem cell transplantation. In patients with persistent cerebrospinal fluid lymphoma after cycle 1, the intrathecal rituximab was replaced by intrathecal triple therapy, with MTX, cytarabine, and dexamethasone.Thirty-six patients were included. Eighteen had evidence of cerebrospinal fluid lymphoma, 24 had brain parenchymal disease, and 20 (56%) had concurrent systemic disease. The overall response rate after 2 R-DHAP-MTX was 53% (19/36), with 22% (8/36) complete remission. Fifteen patients (42%) underwent a transplant. One-year progression-free survival was 19% (95% confidence interval, 9-34): 25% in patients without and 15% in patients with systemic disease. One-year overall survival was 25% (95% confidence interval, 12-40). This treatment regimen did not result in a major improvement of outcome of secondary CNS lymphoma, especially when concurrent systemic disease was present.Registered in the Dutch trial register www. trialregister.nl, NTR1757; EudraCT number 2006-002141-37.

American College of Rheumatology (ACR) response criteria is used to assess improvement in tender and swollen joint counts and in 3 of the 5 core measures (acute-phase reactant, physician global assessment, patient global assessment, pain, and physical function). From the clinical trial data on 5 approved biological products for the treatment of rheumatoid arthritis, population pharmacokinetic/pharmacodynamic models were developed to quantitatively describe the relationship between exposure and response rates of 3 individual components of ACR response criteria. The models were then used to simulate the clinical outcomes at various time points following different treatment regimens. The relative sensitivity of these criteria components was assessed using power analysis. As compared to the composite endpoints (ACR20/ACR50/ACR70), the individual ACR criteria components had adequate power and higher sensitivity in distinguishing treatment effects over placebo/methotrexate control. The 3 individual ACR criteria components appeared to have similar powers at different dose levels after long-term treatment. This research provides a unique approach to assess the relative sensitivity of the 3 binary components of ACR response criteria which would be useful to support future dose selection and trial design in the treatment of rheumatoid arthritis.

Clinical trials enrolling follicular lymphoma (FL) patients typically require bone marrow biopsies (BMBs) at baseline and at a subsequent point if complete response is achieved. These procedures are painful, take time and add cost. We hypothesized that BMBs do not provide information significant for response assessment in most follicular lymphoma patients on clinical trials. We identified 99 patients treated on clinical trials for follicular lymphoma between 2000 and 2016. BMBs resulted in a possible response assessment change in 1·0% of patients (95% confidence interval: 0·0-5·5%). We conclude that mandatory BMBs at baseline and for response assessment are unnecessary in clinical trials for follicular lymphoma.

BACKGROUND: The current study was conducted to expedite international standardized reporting of bone marrow disease in children with neuroblastoma and to improve equivalence of care. METHODS: A multidisciplinary International Neuroblastoma Response Criteria Bone Marrow Working Group was convened by the US National Cancer Institute in January 2012 with representation from Europe, North America, and Australia. Practical transferable recommendations to standardize the reporting of bone marrow disease were developed. RESULTS: To the authors' knowledge, the current study is the first to comprehensively present consensus criteria for the collection, analysis, and reporting of the percentage area of bone marrow parenchyma occupied by tumor cells in trephine-biopsies. The quantitative analysis of neuroblastoma content in bone marrow aspirates by immunocytology and reverse transcriptase-quantitative polymerase chain reaction are revised. The inclusion of paired-like homeobox 2b (PHOX2B) for immunohistochemistry and reverse transcriptase-quantitative polymerase chain reaction is recommended. Recommendations for recording bone marrow response are provided. The authors endorse the quantitative assessment of neuroblastoma cell content in bilateral core needle biopsies-trephines and aspirates in all children with neuroblastoma, with the exception of infants, in whom the evaluation of aspirates alone is advised. It is interesting to note that 5% disease is accepted as an internationally achievable level for disease assessment. CONCLUSIONS: The quantitative assessment of neuroblastoma cells is recommended to provide data from which evidence-based numerical criteria for the reporting of bone marrow response can be realized. This is particularly important in the minimal disease setting and when neuroblastoma detection in bone marrow is intermittent, where clinical impact has yet to be validated. The wide adoption of these harmonized criteria will enhance the ability to compare outcomes from different trials and facilitate collaborative trial design.

Rheumatologists face unique challenges in discriminating between rheumatologic and non-rheumatologic disorders with similar manifestations, and in discriminating among rheumatologic disorders with shared features. The majority of rheumatic diseases are multisystem disorders with poorly understood etiology; they tend to be heterogeneous in their presentation, course, and outcome, and do not have a single clinical, laboratory, pathological, or radiological feature that could serve as a “gold standard” in support of diagnosis and/or classification. Thus, the development of criteria for use in routine clinical care and in clinical research has been an important focus in rheumatology. Improved understanding of disease pathogenesis and new diagnostic tools have led to reexamination of existing classification and diagnostic criteria with updated classification criteria for some diseases being endorsed recently (1, 2). The American College of Rheumatology (ACR) Subcommittee on Classification and Response Criteria is responsible for guiding the development and validation of new classification and response criteria that are eventually considered for ACR endorsement. This includes review of proposals for the development of new criteria sets and providing the ACR leadership with recommendations for development and approval of new classification and response criteria sets (1, 3–5). The Subcommittee has previously published a guidance paper for the development of classification and response criteria (6). This prior work has provided details about the rationale for the ACR’s position on classification criteria, but clarification around the issue of diagnostic criteria was lacking. Indeed, the ACR endorsed preliminary diagnostic criteria for fibromyalgia (7) in 2010, which prompted discussions about whether the Subcommittee should also support the development and ACR endorsement of diagnostic criteria, in addition to that of classification and response criteria. The primary objectives of this current article, by former and current members of the Subcommittee on Classification and Response Criteria, are to compare diagnostic and classification criteria, using specific examples from the published literature, and to clarify the ACR’s position on both types of criteria.

BACKGROUND The categories of the International Myeloma Working Group (IMWG) response criteria for multiple myeloma are based on the magnitude of the change in paraprotein and the normalization of the free light chain ratio (rFLC). However, the relationship between the response by these biomarkers and clinical outcomes has not been validated with novel compounds in the phase 1 setting. Early response predictors may have prognostic value and speed development plans for new agents. METHODS The relationship between biomarkers of response and clinical outcomes was examined in 87 relapsed or refractory multiple myeloma patients enrolled in nontransplant phase I clinical trials from January 2004 through November 2011 at 4 time landmarks. Progression-free survival (PFS) was the primary outcome, and overall survival (OS) was also assessed. RESULTS The normalization of rFLC within 4 months predicted improvement in PFS (11.3 vs 2.8 months, P = .038), whereas the normalization of rFLC within 12 months predicted improvement in PFS (6.1 vs 2.8 months, P = .015) and OS (45 vs 17.4 months, P = .002). The magnitude of response in paraprotein predicted and correlated linearly with PFS at all time landmarks (R2 = 0.703-0.943) when it was assessed with 2 different boundaries. CONCLUSIONS These findings suggest that the normalization of rFLC and the magnitude of response are viable biomarkers for surrogate endpoints in early-phase clinical trials, validate the use of current IMWG response criteria in the phase 1 setting, and support the use of these biomarkers for drug development endpoints. Cancer 2015;121:853–862. © 2014 American Cancer Society.

Objective To examine the association of the American College of Rheumatology (ACR) response criteria (20% improvement [ACR20], ACR50, and ACR70) and the European League Against Rheumatism (EULAR) response criteria with patient-reported improvement in rheumatoid arthritis (RA) activity. Methods Two hundred fifty patients with active RA were studied prospectively, before and after escalation of antirheumatic treatment. Patients were asked to report if they subjectively judged that they had experienced important improvement with treatment, and the proportion of patients who reported improvement was compared with the proportion who met the ACR20, ACR50, ACR70, and EULAR response criteria. Results Improvement in overall arthritis status was reported by 167 patients (66.8%), while 107 patients (42.8%) had an ACR20 response, 52 (20.8%) had an ACR50 response, 24 (9.6%) had an ACR70 response, and 136 (54.4%) had a EULAR moderate/good response. ACR20 response had a sensitivity of 0.57 and a specificity of 0.85 for clinically important improvement as judged by patients. Sensitivities of the ACR50, ACR70, and EULAR moderate/good responses were 0.30, 0.14, and 0.68, respectively, while their specificities were 0.97, 0.99, and 0.73, respectively. The ACR hybrid score with the highest sensitivity and specificity for important improvement was 19.99. Conclusion Among patients with active RA, ACR20 responses are highly specific measures of improvement as judged by patients, but exclude a substantial proportion of patients who consider themselves improved. Response criteria are associated with, but not equivalent to, patient-perceived improvement.

High levels of the nutrients nitrogen and phosphorus can cause unhealthy biological or ecological conditions in surface waters and prevent the attainment of their designated uses. Regulatory agencies are developing numeric criteria for these nutrients in an effort to ensure that the surface waters in their jurisdictions remain healthy and productive, and that water quality standards are met. These criteria are often derived using field measurements that relate nutrient concentrations and other water quality conditions to expected biological responses such as undesirable growth or changes in aquatic plant and animal communities. Ideally, these numeric criteria can be used to accurately “diagnose” ecosystem health and guide management decisions. However, the degree to which numeric nutrient criteria are useful for decision making depends on how accurately they reflect the status or risk of nutrient-related biological impairments. Numeric criteria that have little predictive value are not likely to be useful for managing nutrient concerns. This paper presents information on the role of numeric nutrient criteria as biological health indicators, and the potential benefits of sufficiently accurate criteria for nutrient management. In addition, it describes approaches being proposed or adopted in states such as Florida and Maine to improve the accuracy of numeric criteria and criteria-based decisions. This includes a preference for developing site-specific criteria in cases where sufficient data are available, and the use of nutrient concentration and biological response criteria together in a framework to support designated use attainment decisions. Together with systematic planning during criteria development, the accuracy of field-derived numeric nutrient criteria can be assessed and maximized as a part of an overall effort to manage nutrient water quality concerns. Integr Environ Assess Manag 2014;10:133–137. © 2013 SETAC

Criteria for new drug approval include demonstration of efficacy. In neuro-oncology, this is determined radiographically utilizing tumor measurements on MRI scans. Limitations of this method have been identified where drug activity is not reflected in decreased tumor size. The RANO (Response Assessment in Neuro-Oncology) working group was established to address limitations in defining endpoints for clinical trials in adult neuro-oncology and to develop standardized response criteria. RAPNO was subsequently established to address unique issues in pediatric neuro-oncology. The aim of this paper is to delineate response criteria issues in pediatric clinical trials as a basis for subsequent recommendations.

Apart from indolent systemic mastocytosis (SM), which is associated with a favorable prognosis, other subtypes of SM (SM with associated clonal hematologic non-mast cell lineage disease, aggressive SM, and mast cell leukemia - collectively referred to in this review as advanced SM) can be debilitating. The complexity of SM makes both the diagnosis and design of response criteria challenging for clinical studies. The tyrosine kinase KIT has been shown to play a crucial role in the pathogenesis of SM and has been a focal point in the development of targeted therapy. Mutations within various domains of the KIT receptor that lead to constitutive activation have been identified in patients, and those involving the activation loop of the KIT receptor are the mutations most frequently detected in patients with mastocytosis. Aberrant activation of the KIT receptor results in increased production of mast cells in extracutaneous organs that may lead to organ failure or early death. This review discusses the diagnosis and management of patients with advanced SM, including the relevance of KIT in this disease, potential therapies targeting this kinase, and criteria for measuring responses to these therapies.

Whether or not bone marrow biopsies should be performed routinely in patients with skin lesions that show histological features consistent with an indolent B-cell lymphoma [marginal zone lymphoma (MZL) or follicle centre lymphoma (FCL)] has been debated. As no studies have addressed this question for this group of lymphomas, we evaluated the results of bone marrow biopsy examination in 275 patients with histological features consistent with MZL (n = 82) or FCL (n = 193) first presenting in the skin. In the MZL group, two of 82 patients (2%) showed bone marrow involvement, which was the only extracutaneous localization in one of these patients. In the FCL group, 22 of 193 patients (11%) had bone marrow involvement and was the only extracutaneous localization in nine of them. FCL patients with skin lesions and a positive bone marrow had a significantly worse prognosis when compared with patients with only skin lesions (5-year disease-specific survival 63% vs. 95%; P = 0.001). These results indicate that bone marrow investigation is essential for staging patients with a FCL first presenting in the skin. Bone marrow examination appears to have limited value in patients with MZL presenting in the skin.

Positron emission tomography (PET)/computerised tomography (CT) has proved useful in a number of haematological malignancies, particularly in Hodgkin lymphoma (HL) and aggressive non-Hodgkin lymphomas (NHL). It is recommended in the staging of HL and aggressive NHL, it has been shown to be prognostically important early during treatment, and it has been incorporated in the response criteria. However, treatment modification based on early scans is still experimental, and routine use in follow up cannot be recommended. The use of PET/CT in other lymphoma types and other haematological malignancies is still under evaluation.

Transfusion-related morbidity is an emerging challenge in chronically transfused patients with low-risk myelodysplastic syndromes (MDS). In these patients, transfusion-induced iron overload may represent a leading medical problem. However, although iron-chelating drugs are available, little is known about optimal diagnostic tools, predisposing factors, and the optimal management of these patients. In the current article, we provide recommendations for the diagnosis, prevention and treatment of iron overload in MDS and propose treatment response criteria. Consensus criteria and resulting recommendations were discussed and formulated by members of the MDS platform of the Austrian Society of Haematology and Oncology in a series of meetings and conferences in 2006 and 2007. These recommendations should facilitate and assist in recognition of iron overload, selection of patients, timing of treatment, drug selection and the measurement of treatment responses. Eur J Clin Invest 2008

RELEVANCE TO THE CLINICIAN: Clinicians already know that not all patients who are diagnosed with rheumatic diseases really have them. Moreover, determining which patients have improved and by how much is also difficult. Classification criteria allow clinical researchers to recruit patients with similar diseases (e.g., rheumatoid arthritis or systemic lupus erythematosus) into studies. Response criteria help to determine whether treatments really work, i.e., whether they actually produce clinically important improvement. As the science of clinical research advances, we must update our standards for considering classification and response criteria. In this editorial, members of the American College of Rheumatology (ACR) Subcommittee on Classification and Response Criteria describe the purpose of criteria sets, their development and validation, and the role of the ACR in adopting them.

Summary Background : Satisfactory treatment options for functional dyspepsia are lacking. Single subject trial designs may identify subgroups of patients with a uniform response to therapy. Aim : To test reproducibility of response in a new random-starting-day trial design developed to identify acid-related symptoms in functional dyspepsia. Methods : One hundred and nineteen patients with functional dyspepsia completed a 12-day, double-blind random-starting-day trial with an initial placebo run-in followed by switch to omeprazole on a randomized and blinded day (between days 5 and 9) with active treatment continuing for the rest of the trial. Response was defined as a sustained ≥50% reduction of a daily symptom-score within 3 days of active treatment. Fifty-nine patients repeated the random-starting-day trial at relapse of symptoms. Results : After exclusion of placebo responders, 14% (15 of 106) were classified as responders in the first and 20% (10 of 50) in the subsequent random-starting-day trial series. Sixty-eight per cent (40 of 59) of the patients reproduced their initial response with a chance-corrected agreement of 0.29. Comparing response patterns using different symptom rating-scales showed good correlation (kappa 0.60). Conclusion : Reproducibility of response in a random-starting-day trial was imperfect, mainly because of the low response rates and strict response criteria. Lack of symptom stability impairs the value of the random-starting-day trial and only patients with frequent and stable symptoms should be evaluated in this design.

Objectives To define what expert clinicians consider a dramatic response in ankylosing spondylitis (AS) patients treated with biologic therapies based on patient and physician assessments of global disease activity. To compare this expert clinician-derived criteria to the Ankylosing Spondylitis Assessment Study (ASAS) Group criteria for improvement. Methods Forty consecutive AS patients were treated in a 1-year open-label protocol with infliximab. Response to treatment at week 52 was defined using ASAS response criteria. For the purpose of this exercise, improvement using ASAS criteria was defined by consensus among experts as good with 50% improvement from baseline (ASAS50) and dramatic with 70% improvement from baseline (ASAS70). Experts established separate criteria for improvement in disease activity as good or dramatic based on patient and physician global assessment of disease activity. Results Twelve of 40 patients met the ASAS70 criteria, however, only 8 met the expert definition of a dramatic improvement based on physician global scores and 5 met the expert definition of a dramatic improvement based on patient global assessment of disease activity. Agreement was poor between ASAS50 or ASAS70 and expert definition of improvement based on physician global scores (κ < 0.3), but agreement was moderate to good between ASAS50 or ASAS70 and expert definition of improvement based on patient global scores, (κ = 0.6–0.7). Conclusions Differential response experienced by AS patients treated with infliximab was adequately captured by the ASAS composite improvement criteria. Overall, this study demonstrates the validity of the ASAS criteria for the detection of improvement in AS patients treated with biologics. However, the patient global assessment of disease activity may be sufficient to monitor changes in disease activity in these patients.

Objective To study the validity of response criteria for rheumatoid arthritis (RA) that included 28-joint counts instead of more comprehensive joint counts. Methods In a double-blind, placebo-controlled trial of 105 patients treated with methotrexate, sulfasalazine, or both, response was evaluated at week 52. Both European League Against Rheumatism and American College of Rheumatology definitions of response, with comprehensive as well as simplified joint counts, were calculated. We studied the differences between the criteria with and without simplified joint counts, the discriminating capacity between treatment groups, and the association with change in functional capacity and joint damage. Results Response criteria that included 28-joint counts classified patients' responses more conservatively. No differences between treatment groups were found with either set of response criteria. The association with change in functional capacity was significant in all cases. All response criteria were significantly associated with radiographic progression of RA. Conclusion Improvement criteria that include 28-joint counts are as valid as the original improvement criteria that included more comprehensive joint counts.

The present paper provides a primer on percentile reinforcement schedules, which have been used for two decades to study response differentiation and shaping in the laboratory. Arranged in applied settings, percentile procedures could be used to specify response criteria, standardizing treatment across subjects, trainers, and times to provide a more consistent training environment while maintaining the sensitivity to the individual's repertoire that is the hallmark of shaping. Percentile schedules are also valuable tools in analyzing the variables of which responding is a function, both inside and outside the laboratory. Finally, by formalizing the rules of shaping, percentile schedules provide a useful heuristic of the processes involved in shaping behavior, even for those situations that may not easily permit their implementation. As such, they may help further sensitize trainers and researchers alike to variables of critical importance in behavior change.

The majority of buildings located at petrochemical plants, exclusive of control rooms, are of conventional construction and do not explicitly provide for resistance to blast loads. Typical construction types include steel frame with metal cladding, concrete masonry unit, and brick clad with concrete or steel frame. These buildings are designed for conventional loads without regard for high overpressures and fragments resulting from an accidental explosion. Current regulatory trends are causing many companies to evaluate design standards for new and existing support structures especially in the wake of recent accidental explosions. Response criteria is an important part of these design standards especially when they are used to analyze existing structures for blast protection. Structural evaluations at several sites have revealed that few existing structures meet current design criteria primarily due to weak member connections. Previous work has shown that many conventional structures can develop a surprising degree of resistance to blast loading if proper detailing is used in design, thus allowing members to develop their full capacity. This paper discusses response criteria currently used for new structures and examines the problem of determining acceptance criteria for existing structures. Data from explosion accidents and test programs is reviewed to determine the degree of conservatism in current criteria. Finally, alternatives for establishing blast capacity of existing structures are discussed.

In empirical research, developmentalists attribute knowledge to children on the basis of performances on assessment tasks. Since knowledge is not itself observable, criteria are needed for reasonable decisions to be made about how to classify different intellectual states, such as false belief, empirically true belief, necessary knowledge. In Piagetian research, there are two distinct views about the selection of such ‘response criteria’. One view states that knowledge can be attributed on the basis of children's judgements-alone (J-view). A contrary view states that such attribution requires children to justify their judgements (JJ-view). An objection to the J-view is discussed by consideration of the two dominant philosophical accounts as to the nature of knowledge, namely the foundationalist and causal accounts. It is argued, firstly, that the foundationalist account requires the elimination of the J-view with which it is incompatible through its failure to deal with cases of knowledge at all. It is argued, secondly, that the causal account places a limitation on the J-view which fails to deal with cases of necessary knowledge. Since one of the main problems in Piagetian research is the construction of necessary knowledge, only the JJ-view should be used when this problem is addressed. Developmental research which is based on the J-view alone could not, without circularity, be concerned with the substantive issues which are outside its conceptual scope.

Purpose: The measurement of mesothelioma is a crucial component of the assessment of disease response to therapy. Current standards for response assessment utilize summed linear measurements acquired on three CT sections. The purpose of this work was to evaluate area measurements as a metric for response assessment, specifically through the study of the inter‐observer variability of such measurements.Method/Materials: One CT scan from each of 21 mesothelioma patients was collected. Using a computer interface, three radiologists contoured the visible disease on three CT sections containing visible disease. The radiologists were able to inspect the full CT scan, but were only able to contour specified sections. The resulting 189 area measurements (three radiologists, three sections per patient, 21 patients) were compared using a random‐effects analysis of variance model to assess relative inter‐observer variability. The 63 sums of three section measurements per patient were also analyzed, since these sums of areas are more clinically relevant for response assessment. Results: When each radiologist's measurements were compared with the average of the other two radiologists'measurements, moderate correlation was observed (r‐values of 0.64 to 0.94). The 95% confidence interval for relative inter‐observer variability of section area measurements was [−81.3%, +433.7%], spanning a range of 515.0%. For the summed area measurements (three sections per patient), the 95% confidence interval for relative inter‐observer variability was [−68.8%, +220.7%], spanning a range of 289.3%. Conclusion: The inter‐observer variability in area measurements of mesothelioma tumor spans a range that encompasses the response categories of the original WHO bi‐dimensional response criteria, as well as extrapolations of the RECIST response categories to two dimensions. Manual area measurements may not be a robust means of response assessment in mesothelioma patients, thus motivating future research in more precise semi‐automated segmentation methods.

Because we found it illogical to attempt measurement of nonmeasurable but visible tumors in patients with advanced lung cancer, we devised and used a separate set of response criteria for patients with evaluable, nonmeasurable tumors. Patients with evaluable disease who had obtained a tumor regression after therapy were compared to patients with measurable disease who had obtained a tumor regression according to standard criteria. Among 191 cases evaluated (54% with measurable and 46% with evaluable disease), 59 tumor regressions were found (35 in patients with measurable disease and 24 in patients with evaluable disease). Evaluating regressions in patients with both types of disease, we could not detect statistical differences in regression rates, times to regression, durations of regression or survival. We believe the response criteria used for patients with evaluable, nonmeasurable lung cancer to be valid in assessing response to therapy.

The ability of whites and blacks to correctly identify previously-seen faces of each race was assessed in a factorial design varying the length of time between inspection and recognition phases (immediate, 2 days, or 7 days) and incentive (possibility of monetary reward for accurate recognition). Recognition of faces of males was poorer after the longer time delays, but no comparable delay over time occurred for pictures of females. Subjects' criteria for responding became more lax after the longer time delays. Incentive had no significant direct impact on recognition accuracy or on subjects' criterion levels. A significant degree of own-race bias in recognition accuracy occurred, but only among whtte subjects. An own-race bias in response criteria occurred with subjects of both races. Implications of these findings are discussed.

The accuracy levels of serial radioisotope bone scans and conventional bone radiographs in assessing the response of bone metastases to systemic therapy were compared in 34 women with metastatic breast cancer. Each patient had measurable or evaluable nonosseous metastases, which were assessed independently of skeletal disease. The bone scan was found to be more accurate and sensitive indicator of the status of bone metastases than the radiograph. The bone scan correlated well with response of soft tissue or visceral disease, while the results of repeated bone radiographs were frequently misleading. With use of a digital model, it was possible to accurately measure the area of skeletal involvement of the bone scan, and from this derive quantitative criteria for response in bone metastases analogous to response criteria currently in use for soft tissue and visceral disease. It is suggested that serial quantitative bone scans be done, in preference to radiographs, to assess the response of bone metastases to systemic therapy.

When the decrease in tumor size is used to evaluate the therapeutic effectiveness of a promising anticancer agent in a short-term clinical trial, it is considered to reflect “objective” response to therapy. This paper discusses the two senses of the word “objective” in the clinical testing situation: (1) objectivity in measuring tumor and (2) objectivity in the evaluation process which utilizes the measurements for classification into response or no response categories. The tumor size data from 1312 patients who received one of five drugs in the Eastern Clinical Drug Program were used for this analysis. The process of evaluating change in tumor size was studied with procedures or criteria for classifying tumor response. The application of various response criteria caused the proportion of responding patients to vary between 0.00 and 0.50; however, regardless of the particular set of response criteria applied to the data, the difference between drugs apparently was maintained.

In order to provide an in vitro fertilization (IVF) service for a large geographic region, we developed the concept of Satellite IVF Centers. The goals of this program were as follows: 1) to facilitate patient participation by decreasing travel expenditures, time for screening appointments, and IVF cycle cancellations, and 2) to involve community physicians in a regionalized program. We established centers in nine cities within the Washington, Alaska, Montana, and Idaho region serviced by the University of Washington, and in Alberta, Canada. A 2-day training session was held to provide participating physicians with a basic knowledge of IVF. We considered the roles of the satellite IVF physician to include identification of couples for IVF, initiation of ovulation induction cycles, and determination of appropriate induction cycles for oocyte recovery. The staff of the University Department of Laboratory Medicine standardized the methodologies for estradiol measurements and maintained a quality control analysis for all participating community laboratories. Satellite activity was coordinated through the IVF office at the University, which monitored physicians' decisions based on hormone and ultrasound data from days 7 and 8 of the stimulation cycle. Patients meeting specific ovarian response criteria arrived at the University on day 9 of the stimulation cycle and completed IVF. During 18 months, 72 patients were screened and initiated cycles at the nine participating centers. Forty-four of these patients were sent to the University for oocyte recovery, which resulted in 39 embryo transfers and eight pregnancies. This service has reached a large geographic community, dramatically reduced the cost of IVF for this community, and met with both patient and physician acceptance.