Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival

Better treatment is required for older patients with acute myeloid leukemia (AML) not considered fit for intensive chemotherapy. We report a randomized comparison of lowdose Ara-C (LDAC) vs the novel nucleoside, clofarabine, in untreated older patients with AML and high-risk myelodysplastic syndrome (MDS). A total of 406 patients with de novo (62%), secondary disease (24%), or high-risk MDS (>10% marrow blasts) (15%), median age 74 years, were randomized to LDAC 20 mg twice daily for 10 days every 6 weeks or clofarabine 20 mg/m2 on days 1 to 5, both for up to 4 courses. These patients had more adverse demographics than contemporaneous intensively treated patients. The overall remission rate was 28%, and 2-year survival was 13%. Clofarabine significantly improved complete remission (22% vs 12%; hazard ratio [HR] 5 0.47 [0.28-0.79]; P 5 .005) and overall response (38% vs 19%; HR 5 0.41 [0.26-0.62]; P < .0001), but there was no difference in overall survival, explained by poorer survival in the clofarabine patients who did not gain complete remission and also following relapse. Clofarabine was more myelosuppressive and required more supportive care. Although clofarabine doubled remission rates, overall survival was not improved overall or in any subgroup. The treatment of patients of the type treated here remains a major unmet need. This trial was registered at www.clinicaltrials.gov as #ISRCTN 11036523.

Effect of questionnaire length, personalisation and reminder type on response rate to a complex postal survey : randomised controlled trial

Background: Minimising participant non-response in postal surveys helps to maximise the generalisability of the inferences made from the data collected. The aim of this study was to examine the effect of questionnaire length, personalisation and reminder type on postal survey response rate and quality and to compare the costeffectiveness of the alternative survey strategies.
Methods: In a pilot study for a population study of travel behaviour, physical activity and the environment, 1000 participants sampled from the UK edited electoral register were randomly allocated using a 2 × 2 factorial design to receive one of four survey packs: a personally addressed long (24 page) questionnaire pack, a personally addressed short (15 page) questionnaire pack, a non-personally addressed long questionnaire pack or a nonpersonally addressed short questionnaire pack. Those who did not return a questionnaire were stratified by initial randomisation group and further randomised to receive either a full reminder pack or a reminder postcard. The effects of the survey design factors on response were examined using multivariate logistic regression.
Results: An overall response rate of 17% was achieved. Participants who received the short version of the questionnaire were more likely to respond (OR = 1.48, 95% CI 1.06 to 2.07). In those participants who received a reminder, personalisation of the survey pack and reminder also increased the odds of response (OR = 1.44, 95% CI 1.01 to 1.95). Item non-response was relatively low, but was significantly higher in the long questionnaire than the short (9.8% vs 5.8%; p = .04). The cost per additional usable questionnaire returned of issuing the reminder packs was £23.1 compared with £11.3 for the reminder postcards.
Conclusions: In contrast to some previous studies of shorter questionnaires, this trial found that shortening a relatively lengthy questionnaire significantly increased the response. Researchers should consider the trade off between the value of additional questions and a larger sample. If low response rates are expected, personalisation may be an important strategy to apply. Sending a full reminder pack to non-respondents appears a worthwhile, albeit more costly, strategy.

Peginterferon plus ribavirin and sustained virological response rate in HCV-related advanced fibrosis: a real life study

Background: Tolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. Methods: A multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. Results: 308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p = 0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. Conclusion: Treatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment.

Phenobarbital for neonatal seizures:response rate and predictors of refractoriness

Background : Phenobarbital is the first-line choice for neonatal seizures treatment, despite a response rate of approximately 45%. Failure to respond to acute anticonvulsants is associated with poor neurodevelopmental outcome, but knowledge on predictors of refractoriness is limited. Objective : To quantify response rate to phenobarbital and to establish variables predictive of its lack of efficacy. Methods : We retrospectively evaluated newborns with electrographically confirmed neonatal seizures admitted between January 1999 and December 2012 to the neonatal intensive care unit of Parma University Hospital (Italy), excluding neonates with status epilepticus. Response was categorized as complete (cessation of clinical and electrographic seizures after phenobarbital administration), partial (reduction but not cessation of electrographic seizures with the first bolus, response to the second bolus), or absent (no response after the second bolus). Multivariate analysis was used to identify independent predictors of refractoriness. Results : Out of 91 newborns receiving phenobarbital, 57 (62.6%) responded completely, 15 (16.5%) partially, and 19 (20.9%) did not respond. Seizure type (p = 0.02), background electroencephalogram (EEG; p ≤ 0.005), and neurologic examination (p ≤ 0.005) correlated with response to phenobarbital. However, EEG (p ≤ 0.02) and seizure type (p ≤ 0.001) were the only independent predictors. Conclusion : Our results suggest a prominent role of neurophysiological variables (background EEG and electrographic-only seizure type) in predicting the absence of response to phenobarbital in high-risk newborns.

Use of an on-line student response system : an analysis of adoption and continuance

The goal of this project was to initiate the use of an internet-based student response system in a large, first year chemistry class at a typical Australian university, and to verify its popularity and utility. A secondary goal was to influence other academic staff to adopt the system, initiating change at the discipline and Faculty level. The first goal was achieved with a high response rate using a commercial on-line system; however, the number of students engaging with the system dropped gradually during each class and over the course of the semester. Factors affecting student and staff adoption and continuance with technology are explored using established models.

Non-response bias in randomized control experiments in criminology : putting the Queensland Community Engagement Trial (QCET) under a microscope

Objectives The goal of this article is to examine whether or not the results of the Queensland Community Engagement Trial (QCET)-a randomized controlled trial that tested the impact of procedural justice policing on citizen attitudes toward police-were affected by different types of nonresponse bias. Method We use two methods (Cochrane and Elffers methods) to explore nonresponse bias: First, we assess the impact of the low response rate by examining the effects of nonresponse group differences between the experimental and control conditions and pooled variance under different scenarios. Second, we assess the degree to which item response rates are influenced by the control and experimental conditions. Results Our analysis of the QCET data suggests that our substantive findings are not influenced by the low response rate in the trial. The results are robust even under extreme conditions, and statistical significance of the results would only be compromised in cases where the pooled variance was much larger for the nonresponse group and the difference between experimental and control conditions was greatly diminished. We also find that there were no biases in the item response rates across the experimental and control conditions. Conclusion RCTs that involve field survey responses-like QCET-are potentially compromised by low response rates and how item response rates might be influenced by the control or experimental conditions. Our results show that the QCET results were not sensitive to the overall low response rate across the experimental and control conditions and the item response rates were not significantly different across the experimental and control groups. Overall, our analysis suggests that the results of QCET are robust and any biases in the survey responses do not significantly influence the main experimental findings.

Surveillance during pregnancy: methods and response rates from a hospital based pilot study of the Pregnancy Risk Assessment Monitoring System in Ireland

Background: Many European countries including Ireland lack high quality, on-going, population based estimates of maternal behaviours and experiences during pregnancy. PRAMS is a CDC surveillance program which was established in the United States in 1987 to generate high quality, population based data to reduce infant mortality rates and improve maternal and infant health. PRAMS is the only on-going population based surveillance system of maternal behaviours and experiences that occur before, during and after pregnancy worldwide.Methods: The objective of this study was to adapt, test and evaluate a modified CDC PRAMS methodology in Ireland. The birth certificate file which is the standard approach to sampling for PRAMS in the United States was not available for the PRAMS Ireland study. Consequently, delivery record books for the period between 3 and 5 months before the study start date at a large urban obstetric hospital [8,900 births per year] were used to randomly sample 124 women. Name, address, maternal age, infant sex, gestational age at delivery, delivery method, APGAR score and birth weight were manually extracted from records. Stillbirths and early neonatal deaths were excluded using APGAR scores and hospital records. Women were sent a letter of invitation to participate including option to opt out, followed by a modified PRAMS survey, a reminder letter and a final survey.Results: The response rate for the pilot was 67%. Two per cent of women refused the survey, 7% opted out of the study and 24% did not respond. Survey items were at least 88% complete for all 82 respondents. Prevalence estimates of socially undesirable behaviours such as alcohol consumption during pregnancy were high [>50%] and comparable with international estimates.Conclusion: PRAMS is a feasible and valid method of collecting information on maternal experiences and behaviours during pregnancy in Ireland. PRAMS may offer a potential solution to data deficits in maternal health behaviour indicators in Ireland with further work. This study is important to researchers in Europe and elsewhere who may be interested in new ways of tailoring an established CDC methodology to their unique settings to resolve data deficits in maternal health.

Improving Indwelling Glucose Sensor Performance: Porous, Dexamethasone-Releasing Coatings that Modulate the Foreign Body Response

Inflammation and the formation of an avascular fibrous capsule have been identified as the key factors controlling the wound healing associated failure of implantable glucose sensors. Our aim is to guide advantageous tissue remodeling around implanted sensor leads by the temporal release of dexamethasone (Dex), a potent anti-inflammatory agent, in combination with the presentation of a stable textured surface.

First, Dex-releasing polyurethane porous coatings of controlled pore size and thickness were fabricated using salt-leaching/gas-foaming technique. Porosity, pore size, thickness, drug release kinetics, drug loading amount, and drug bioactivity were evaluated. In vitro sensor functionality test were performed to determine if Dex-releasing porous coatings interfered with sensor performance (increased signal attenuation and/or response times) compared to bare sensors. Drug release from coatings monitored over two weeks presented an initial fast release followed by a slower release. Total release from coatings was highly dependent on initial drug loading amount. Functional in vitro testing of glucose sensors deployed with porous coatings against glucose standards demonstrated that highly porous coatings minimally affected signal strength and response rate. Bioactivity of the released drug was determined by monitoring Dex-mediated, dose-dependent apoptosis of human peripheral blood derived monocytes in culture.

The tissue modifying effects of Dex-releasing porous coatings were accessed by fully implanting Tygon® tubing in the subcutaneous space of healthy and diabetic rats. Based on encouraging results from these studies, we deployed Dex-releasing porous coatings from the tips of functional sensors in both diabetic and healthy rats. We evaluated if the tissue modifying effects translated into accurate, maintainable and reliable sensor signals in the long-term. Sensor functionality was accessed by continuously monitoring glucose levels and performing acute glucose challenges at specified time points.

Sensors treated with porous Dex-releasing coatings showed diminished inflammation and enhanced vascularization of the tissue surrounding the implants in healthy rats. Functional sensors with Dex-releasing porous coatings showed enhanced sensor sensitivity over a 21-day period when compared to controls. Enhanced sensor sensitivity was accompanied with an increase in sensor signal lag and MARD score. These results indicated that Dex-loaded porous coatings were able to elicit a favorable tissue response, and that such tissue microenvironment could be conducive towards extending the performance window of glucose sensors in vivo.

The diabetic pilot animal study showed differences in wound healing patters between healthy and diabetic subjects. Diabetic rats showed lower levels of inflammation and vascularization of the tissue surrounding implants when compared to their healthy counterparts. Also, functional sensors treated with Dex-releasing porous coatings did not show enhanced sensor sensitivity over a 21-day period. Moreover, increased in sensor signal lag and MARD scores were present in porous coated sensors regardless of Dex-loading when compared to bare implants. These results suggest that the altered wound healing patterns presented in diabetic tissues may lead to premature sensor failure when compared to sensors implanted in healthy rats.

A let-7 microRNA-binding site polymorphism in 3'-untranslated region of KRAS gene predicts response in wild-type KRAS patients with metastatic colorectal cancer treated with cetuximab monotherapy

PURPOSE: recent studies have found that KRAS mutations predict resistance to monoclonal antibodies targeting the epidermal growth factor receptor in metastatic colorectal cancer (mCRC). A polymorphism in a let-7 microRNA complementary site (lcs6) in the KRAS 3' untranslated region (UTR) is associated with an increased cancer risk in non-small-cell lung cancer and reduced overall survival (OS) in oral cancers. We tested the hypothesis whether this polymorphism may be associated with clinical outcome in KRAS wild-type (KRASwt) mCRC patients treated with cetuximab monotherapy.

PATIENTS AND METHODS: the presence of KRAS let-7 lcs6 polymorphism was evaluated in 130 mCRC patients who were enrolled in a phase II study of cetuximab monotherapy (IMCL-0144). Genomic DNA was extracted from dissected formalin-fixed paraffin-embedded tumor tissue, KRAS mutation status and polymorphism were assessed using direct sequencing and PCR restriction fragment length polymorphism technique.

RESULTS: KRAS let-7 lcs6 polymorphism was found to be related to object response rate (ORR) in mCRC patients whose tumors had KRASwt. The 12 KRASwt patients harboring at least a variant G allele (TG or GG) had a 42% ORR compared with a 9% ORR in 55 KRASwt patients with let-7 lcs6 TT genotype (P = 0.02, Fisher's exact test). KRASwt patients with TG/GG genotypes had trend of longer median progression-free survival (3.9 versus 1.3 months) and OS (10.7 versus 6.4 months) compared to those with TT genotypes.

CONCLUSIONS: these results are the first to indicate that the KRAS 3'UTR polymorphism may predict for cetuximab responsiveness in KRASwt mCRC patients, which warrants validation in other clinical trials.

Response rates in telephone surveys: managing contactability

Telephone interviewing is the major data collection method for the market research industry. Although social trends such as mobile phones and call screening make it harder to contact people, better technology and contact regimes can assist companies to ameliorate the situation. A study of fieldwork managers responsible for over 75% of all phone interviews in Australia revealed limited use of contact enhancing strategies such as longer survey periods and more callbacks. Commercial imperatives for timely surveys and a lack of end-user concern for response rate issues, along with costs concerns, were believed to be responsible.

Modeling response rates in surveys of female sexual difficulty and dysfunction

INTRODUCTION: Studies that address sensitive topics, such as female sexual difficulty and dysfunction, often achieve poor response rates that can bias  results. Factors that affect response rates to studies in this area are not well characterized.
AIM: To model the response rate in studies investigating the prevalence of female sexual difficulty and dysfunction.
METHODS: Databases were searched for English-language, prevalence studies using the search terms: sexual difficulties/dysfunction, woman/women/female, prevalence, and cross-sectional. Studies that did not report response rates or were clinic-based were excluded. A multiple linear regression model was constructed.
MAIN OUTCOME MEASURES: Published response rates.
RESULTS: A total of 1,380 publications were identified, and 54 of these met our inclusion criteria. Our model explained 58% of the variance in response rates of studies investigating the prevalence of difficulty with desire, arousal, orgasm, or sexual pain (R(2) = 0.581, P = 0.027). This model was based on study design variables, study year, location, and the reported prevalence of each type of sexual difficulty. More recent studies (beta = -1.05, P = 0.037) and studies that only included women over 50 years of age (beta = -31.11, P = 0.007) had lower response rates. The use of face-to-face interviews was associated with a higher response rate (beta = 20.51, P = 0.036). Studies that did not include questions regarding desire difficulties achieved higher response rates than those that did include questions on desire difficulty (beta = 23.70, P = 0.034).
CONCLUSION: Response rates in prevalence studies addressing female sexual difficulty and dysfunction are frequently low and have decreased by an average of just over 1% per anum since the late 60s. Participation may improve by conducting interviews in person. Studies that investigate a broad range of ages may be less representative of older women, due to a poorer response in older age groups. Lower response rates in studies that investigate desire difficulty suggest that sexual desire is a particularly sensitive topic.

Estimating non-response bias in a web-based survey of technology acceptance : a case study of unit guide information systems

Surveys are mostly challenged by response rates. Among the various types of survey research, web-based (internet-based/electronic/online) surveys are commonly used for data collection for a geographically diverse population. In surveys with high/low response rates, non-response bias can be a major concern. While it is not always possible to measure the actual bias due to non-response there are different approaches and techniques that help to identify reasons of non-response bias. The aims of this paper are twofold. (1) To provide an appropriate, interesting and important non-response bias case study for future web-based surveys that will provide guidance to other Information Systems researchers. The case-study concerns an online-survey to evaluate a technology acceptance model for Unit Guide Information systems (UGIS). (2) To discuss how nonresponse bias in a web-based technology acceptance study of an information system (UGIS in this case) can be contained and managed.

Response rates in Australian market research

RICA commissioned Deakin University to “establish whether response rates are in decline in the Australian market research industry and to identify, as far as possible, the reasons for these declines if they exist. This is likely to involve a review of previous research, a literature review and collection of data on response rates provided on a confidential basis and with the assistance of AMSRO to facilitate data provision.”

Attempts were made to contact all listed market research companies in Australia, including all major internet panel companies. While industry co-operation was not high with the study, sufficient data was provided to depict current response rates and to show how they had declined over time. Because of the low contactability issues, this Report proposes the use of better methods to compute the reliability of survey estimates by taking account of past survey results.

The literature review revealed a wealth of recent studies, with the main emphasis being on studies of telephone and internet surveys. This review of the research produced 34 evidence-based guidelines for social researchers. While some of these reflect current practice, the emergence of the internet as the main survey method raises a number of disclosure and sampling issues. Esomar (2012) has produced 28 issues to be raised with providers, which sets the basis for good industry practice. This suggests an opportunity for the industry to adopt these standards as its own and to conduct training courses for major clients and suppliers. There are many panel providers, some of whom are not AMSRO members. AMSRO may need to examine what role it can play in mandating or encouraging adherence to these standards as a way of promoting the industry.

Talks with key industry people, as well as the literature, have revealed the importance of blended surveys, where multiple contact and response mechanisms are used. Particularly where an internet panel is used as one source, this poses representativeness and weighting issues which are difficult to resolve. The Report recommends that where blended survey methods are used, measures be taken to measure contactability in the other contact media, along with more sophisticated weighting schemes. The industry should examine its training courses to ensure that industry expertise keeps pace with these developments.
Summary of Results

The results focus on two main collection methods – the telephone and the internet. As far as the telephone is concerned response rates have been in a gradual decline the last decade. This outcome is hard to detect because the data show considerable fluctuations from one survey wave to the next. Among cold-calling surveys, telephone response rates are typically below 10%, for a range of topics and survey types. Co-operation rates, (the ratio of obtained interviews to refusals) are typically below 0.2 (that is below one interview to five refusals). Telephone interviews with clients have a higher response rate – typically above 20% with co-operation rates above 1.0. It would appear that some topics, such as financial services, may induce a lower level of co-operation. Government sponsored surveys have higher response rates, at times over 50%, but even here a sharp decline in response rates over time for one long running monitor was observed. Co-operation rates were also higher in government sponsored surveys.

One long data series from a telephone omnibus suggested that the “Do Not Call Register” which began in May, 2007 had some positive effects for the industry. Initially there was a spike in both response rates and co-operation. Although this was relatively short-lived, response rates thereafter declined more slowly and co-operation rates were somewhat higher and remained stable. These conclusions should be regarded as tentative as more data series would really be necessary to see if similar trends occurred elsewhere.

As far as the internet is concerned, panel response rates are around the 20% mark and appear to be relatively stable over the last few years. In this case, the gross response rate is the number of interviews divided by the number of invitations sent. As the number of invitations may be a function of the need to fill a survey quickly, it should be considered a gross indicator of response. In order to capture this phenomenon, a further measure has been devised, termed the “attempt rate” which measures the percentage of people who attempt to participate once sent the invitation. The available data suggests that it is relatively stable. However, it is also somewhat susceptible to the time the survey was left open. Finally, a co-operation rate was also calculated. It measures the ratio of completed to terminated interviews, typically at least five interviews to each termination, but often much higher. This measure is not directly comparable with the co-operation rate in telephone surveys because it cannot take account of the number of eligible people on the panel who open the invitation, see the company doing the survey or its length and decide not to take the survey. For internet client studies, response rates were typically somewhat higher than shown for the panels, but there was marked variability.

There was only one study provided of intercept interviews. It showed response rates of over 60% and co-operation rates of nearly 2 interviews per refusal. A strength and a weakness of intercept interviewing is the ability to be selective in who is asked to participate. As for mail, one government sponsored mail survey from 2010 is reported, with a response rate over 50%. The previous review contains more data, as mail appears to be infrequently used within the industry for commercial surveys.

While surveys remain a major and highly effective tool for the industry and its clients, issues with contactability and co-operation mean that even closer attention is needed to survey design, sampling, weighting and analysis than was previously the case.

HER-2, p53, p21 and hormonal receptors proteins expression as predictive factors of response and prognosis in locally advanced breast cancer treated with neoadjuvant docetaxel plus epirubicin combination

Abstract Background Neoadjuvant chemotherapy has been considered the standard care in locally advanced breast cancer. However, about 20% of the patients do not benefit from this clinical treatment and, predictive factors of response were not defined yet. This study was designed to evaluate the importance of biological markers to predict response and prognosis in stage II and III breast cancer patients treated with taxane and anthracycline combination as neoadjuvant setting. Methods Sixty patients received preoperative docetaxel (75 mg/m2) in combination with epirubicin (50 mg/m2) in i.v. infusion in D1 every 3 weeks after incisional biopsy. They received adjuvant chemotherapy with CMF or FEC, attaining axillary status following definitive breast surgery. Clinical and pathologic response rates were measured after preoperative therapy. We evaluated the response rate to neoadjuvant chemotherapy and the prognostic significance of clinicopathological and immunohistochemical parameters (ER, PR, p51, p21 and HER-2 protein expression). The median patient age was 50.5 years with a median follow up time 48 months after the time of diagnosis. Results Preoperative treatment achieved clinical response in 76.6% of patients and complete pathologic response in 5%. The clinical, pathological and immunohistochemical parameters were not able to predict response to therapy and, only HER2 protein overexpression was associated with a decrease in disease free and overall survival (P = 0.0007 and P = 0.003) as shown by multivariate analysis. Conclusion Immunohistochemical phenotypes were not able to predict response to neoadjuvant chemotherapy. Clinical response is inversely correlated with a risk of death in patients submitted to neoadjuvant chemotherapy and HER2 overexpression is the major prognostic factor in stage II and III breast cancer patients treated with a neoadjuvant docetaxel and epirubicin combination.