Augmented pseudo-likelihood estimation for two-phase studies

In many public health and medical research settings, information on key covariates may not be readily available or too expensive to gather for all individuals in the study. In such settings, the two-phase design provides a way forward by first stratifying an initial (large) phase I sample on the basis of covariates readily available (including, possibly, the outcome), and sub-sampling participants at phase II to collect the expensive measure(s). When the outcome of interest is binary, several methods have been proposed for estimation and inference for the parameters of a logistic regression model, including weighted likelihood, pseudo-likelihood and maximum likelihood. Although these methods yield consistent estimation and valid inference, they do so solely on the basis of the phase I stratification and the detailed covariate information obtained at phase II. Moreover, they ignore any additional information that is readily available at phase I but was not used as part of the stratified sampling design. Motivated by the potential for efficiency gains, especially concerning parameters corresponding to the additional phase I covariates, we propose a novel augmented pseudo-likelihood estimator for two-phase studies that makes use of all available information. In contrast to recently-proposed weighted likelihood-based methods that calibrate to the influence function of the model of interest, the methods we propose do not require the development of additional models and, therefore, enjoy a degree of robustness. In addition, we expand the broader framework for pseudo-likelihood based estimation and inference to permit link functions for binary regression other than the logit link. Comprehensive simulations, based on a one-time cross sectional survey of 82,887 patients undergoing anti-retroviral therapy in Malawi between 2005 and 2007, illustrate finite sample properties of the proposed methods and compare their performance competing approaches. The proposed method yields the lowest standard errors when the model is correctly specified. Finally, the methods are applied to a large implementation science project examining the effect of an enhanced community health worker program to improve adherence to WHO guidelines for at least four antenatal visits, in Dar es Salaam, Tanzania.

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Adaptation of the DEMQOL-Proxy for routine use in care homes: a cross-sectional study of the reliability and validity of DEMQOL-CH

BMJ Open ◽

10.1136/bmjopen-2018-028045 ◽

2019 ◽

Vol 9 (8) ◽

pp. e028045 ◽

Cited By ~ 1

Author(s):

Laura J Hughes ◽

Nicolas Farina ◽

Thomas E Page ◽

Naji Tabet ◽

Sube Banerjee

Keyword(s):

Phase I ◽

Psychometric Properties ◽

Phase Ii ◽

Reliability And Validity ◽

Cross Sectional Study ◽

Care Staff ◽

Care Homes ◽

Two Phase ◽

Cross Sectional ◽

And Performance

ObjectiveTo investigate the routine use of a measure of quality of life (QoL) in care homes and assess its psychometric properties when used by care staff.DesignA cross-sectional two-phase study.Setting and participantsData were collected from care staff in seven care homes in East Sussex, England.MethodPhase I: The ability of care staff from two care homes to use the DEMQOL-Proxy without interviewer administration was assessed using agreement analysis between a self-administered and interviewer-administered version of the instrument. Based on these findings, DEMQOL-Proxy was adapted into a new version, DEMQOL-CH, for use as a self-administered instrument in care homes. We assessed agreement between the new DEMQOL-CH and DEMQOL-Proxy to ensure DEMQOL-CH was used correctly. Phase II: A preliminary assessment of the psychometric properties of DEMQOL-CH when used routinely was completed in a further five care homes.ResultsPhase I: Nineteen care staff from two care homes completed QoL measurements for residents. Systematic error was identified when staff self-completed the DEMQOL-Proxy without an interviewer. We modified the DEMOoL-Proxy to create DEMQOL-CH; this reduced the error, producing a version that could be used more accurately by care staff. Phase II: Eleven care staff from five care homes rated resident QoL routinely. DEMQOL-CH showed acceptable psychometric properties with satisfactory reliability and validity and a clear factor structure.ConclusionsThe research presents positive preliminary data on the acceptability, feasibility and performance of routine QoL measurement in care homes using an adapted version of DEMQOL-Proxy, the DEMQOL-CH. Results provide evidence to support the concept that routine measurement of QoL may be possible in care homes. Research is needed to refine and test the methodology and instrument further and to explore the potential for benefits to residents, staff and care homes in larger and more representative populations.

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Implementing Elementary School Nutrition Policy: Principals’ Perspectives

Canadian Journal of Dietetic Practice and Research ◽

10.3148/72.4.2011.e205 ◽

2011 ◽

Vol 72 (4) ◽

pp. e205-e211 ◽

Cited By ~ 15

Author(s):

Jennifer P. Taylor ◽

Debbie MacLellan ◽

Jane Mary Caiger ◽

Kimberley Hernandez ◽

Mary McKenna ◽

...

Keyword(s):

Elementary Schools ◽

Phase I ◽

Phase Ii ◽

Prince Edward Island ◽

Community Support ◽

Nutrition Policy ◽

School Nutrition ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Principals Perceptions

Purpose: We assessed principals’ perceptions about the level of school nutrition policy (SNP) implementation in Prince Edward Island elementary schools, objectively evaluated how closely elementary schools are following SNP regulations for types and frequency of foods offered at school, and explored principals’ beliefs about the key enablers and barriers to SNP implementation. Methods: Phase I involved a cross-sectional survey of principals’ assessment of perceived and actual adherence to SNP components. Phase II included in-depth interviews to explore principals’ perceptions about factors influencing policy adherence. Descriptive statistics were generated. Thematic content analysis was used to identify themes. Results: Forty-one (93%) principals participated in Phase I, and nine of these participated in Phase II. The level of implementation of SNP components varied. Seventy-four percent of all foods sold were categorized as allowed by the SNP; 68% of schools sold at least one “not allowed” food. Key barriers included lost revenue, a higher cost of healthy foods, and limited availability of policy-allowed foods. Enablers were a high level of community support, ready access to food suppliers, and active parent volunteers. Conclusions: While schools are making progress in implementing the SNP, challenges remain. Identifying and communicating strategies for healthy fundraising activities and finding ways to involve parents in SNP implementation are recommended.

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Paid Sick Leave as a Means to Reduce Sickness Presenteeism Among Physicians

Nordic Journal of Working Life Studies ◽

10.18291/njwls.v7i2.81595 ◽

2017 ◽

Vol 7 (2) ◽

Cited By ~ 2

Author(s):

Ingrid Steen Rostad ◽

Ann Fridner ◽

Marie Gustafsson Sendén ◽

Lise Tevik Løvseth

Keyword(s):

Sick Leave ◽

Phase I ◽

Phase Ii ◽

Medical Liability ◽

Family Status ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Sickness Presenteeism ◽

Paid Sick Leave ◽

The Impact

Recurrent international data show that physicians often attend work while ill, termed sickness presenteeism. The current study investigated if sickness presenteeism scores among European physicians varied according to national paid sick leave legislation. We hypothesized that prevalence of presenteeism was higher in countries with lower levels of paid sick leave. We used repeated cross-sectional survey data, phase I (2004/2005, N = 1326) and phase II (2012/2013, N = 1403), among senior consultants at university hospitals in Sweden, Norway, and Italy. Analyses of variances assessed cross-country differences in presenteeism. To assess the impact of country on presenteeism, we used multiple regression analyses controlled for sex, age, family status, work hours, and work content. The results from phase I supported the initial hypothesis. At phase II, presenteeism scores had decreased among the Italian and Swedish sample. The results are discussed with regard to changes in legislation on workhours and medical liability in Italy and Sweden between phase I and II.

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Sustainability of integrated anaemia prevention activities implemented through non-government organizations and schools, and its effect on haemoglobin status of adolescent girls in urban slums of Pune, in Maharashtra, India

Nutrition and Health ◽

10.1177/02601060211009693 ◽

2021 ◽

pp. 026010602110096

Author(s):

Angeline Jeyakumar ◽

Shraddha Chalwadi ◽

Pooja Madhu ◽

Padmini Ghugre

Keyword(s):

Phase I ◽

Needs Assessment ◽

Phase Ii ◽

Adolescent Girls ◽

Service Providers ◽

Phase Iii ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Integrated Intervention ◽

The Impact

Background: Programmes for the prevention of iron deficiency anaemia among adolescent girls need sustainable inputs for maximum benefits. Aim: To assess the interventions sustained for anaemia prevention implemented through NGOs and schools. Methods: An intervention study followed longitudinally in three phases. Phase I comprised (a) needs assessment of the community and (b) capacity assessment of service providers through a cross-sectional survey in nine slums, through six NGOs and three schools. Based on needs assessment, an integrated intervention for anaemia prevention was provided for adolescent girls ( n = 384) in the community. To ensure sustainability the capacity of stakeholders ( n = 67) was built by providing training in the components of the integrated intervention and establishing linkages with the public health system. Refresher training was conducted during phase II ( n = 69) for reinforcing and strengthening of activities introduced in phase I. In phase II and III continuations of activities by the NGOs and schools that were initiated in phase I were monitored. Sustainability of activities was measured using an index that comprised technical, programmatic, social, and financial indicators. The impact of sustained interventions was assessed by comparing the mean rank haemoglobin concentrations of centres with varying levels of coverage. Results: Scores of sustainability indicators decreased from phase II to phase III. Organizations that showed > 50% coverage showed significantly higher mean rank haemoglobin ( p = < 0.05) during phases II and III. Conclusion: There is a need to identify and address barriers that prevent sustainable interventions for anaemia control.

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Nurses’ educational needs when dealing with aggression from patients and their families: a mixed-methods study

BMJ Open ◽

10.1136/bmjopen-2020-041711 ◽

2021 ◽

Vol 11 (1) ◽

pp. e041711

Author(s):

Kana Sato ◽

Yoshimi Kodama

Keyword(s):

Mixed Methods ◽

Nursing Students ◽

Phase I ◽

Phase Ii ◽

Mixed Methods Study ◽

Self Awareness ◽

Two Phase ◽

Sequential Mixed Methods ◽

Nursing Professionals ◽

Educational Contents

ObjectivesTo explore the type of education needed for nurses when dealing with aggression from patients and their families.DesignA two-phase sequential mixed-methods study.SettingThis study was conducted in Japan, with phase I from March to November 2016 and phase II in November 2018.Main outcome measuresThe challenges faced by nurses when dealing with incidents of aggression from the neutral perspective of neither nurse nor patient/family and perceptions of the educational contents developed in this study. Descriptive analyses were used to examine the data retrieved from both phases.ParticipantsPhase I entailed semistructured interviews among 11 neutral-party participants who observed aggressive incidents between nurses and patients/families. Phase II consisted of a web survey conducted among 102 nursing students and 308 nursing professionals.ResultsPhase I resulted in the identification of the following five main educational components: understanding the mechanisms of anger and aggression, maintaining self-awareness, observant listening, managing the self-impression, and communicating based on specific disease characteristics. Each component was related to improved communication through self-awareness. The results of phase II indicated that participants positively perceived these educational contents as likely to be effective for dealing with aggression from patients/families.ConclusionsThis study clarified the type of education needed for nurses when dealing with aggression based on multiple viewpoints. Specifically, neutral-party interviews revealed that communication should be improved through self-awareness. A subsequent survey among nurses and nursing students showed that the identified educational contents were positively received.

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Rigorous Measures are Vital for Preventing and Controlling Coronavirus Disease 2019 (COVID-19): A Cross-sectional Study

10.21203/rs.3.rs-19186/v1 ◽

2020 ◽

Author(s):

Lushi Yu ◽

Yi Wang ◽

Haihua He ◽

Yuxin Chu ◽

Hongyan Feng ◽

...

Keyword(s):

Phase I ◽

Phase Ii ◽

Virus Disease ◽

Control Measures ◽

Ct Image ◽

Cross Sectional ◽

Active Screening ◽

Rapid Isolation ◽

Asymptomatic Patients ◽

Epidemic Area

Abstract Background Since December 2019, a novel corona virus disease named COVID-19 outbreak in Wuhan, China and spread worldwide then. Active prevention and control measures have been carried out in China, such as vigorous publicity, active screening and rapid isolation. As the major epidemic area, the passages in and out of Wuhan were temporarily closed since January 23. We aimed to demonstrate the effectiveness of rigorous measures by comparing the characteristics of patients hospitalized before and after implementation of vital measures. Methods Clinical data of patients admitted to hospital with COVID-19 during January 17-23 (Phase I) and February 3-9 (Phase II) were collected and compared. The cut-off date for follow-up was March 13, 2020. Results Of 176 patients with COVID-19, 97 were admitted in Phase I (43 [44.3%] male; mean age: 47.7), and 79 were in Phase II (33 [41.8%] male; mean age: 50.1). The proportions of severe cases were 21.6% and 10.1% respectively. Fewer patients had comorbidities (13 [16.5%] vs. 7 [7.2%]) and more asymptomatic patients were in Phase II (27.8% vs. 13.9%). Patients in Phase II had less fever (53.2% vs. 70.1%), cough (34.2% vs. 52.6%) and myalgia (11.4% vs.28.9%), while more diarrhea (11.4% vs. 2.1%). Lymphopenia and elevated CRP, as well as eosinopenia and elevated SAA were common in two groups, but all of that were significantly better in Phase II. More patients in Phase II preformed normal CT image on admission (10 [12.7%] vs. 7 [7.2%]). And lower CT scores (3 [2-4] vs. 2 [1-3]) were observed in Phase II. Up to cut-off date, average response time on CT image were 11.2 and 8.1 days in Phase I and II respectively. Shorter average hospitalized days were in Phase II (18.9 vs. 23.3 days). Four patients (4.1%) in Phase I and two (2.5%) in Phase II died. Conclusions Various actions (including vigorous publicity, active screening and rapid isolation) prompted more early patients with COVID-19 found, diagnosed and remedied, leading to good prognosis. Call for pretty attention to the epidemics of COVID-19 and timely measures around the world.

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Mixed methods study protocol to examine perceptions of family medicine among long-term patients of a family medicine clinic in Japan

BMJ Open ◽

10.1136/bmjopen-2020-037113 ◽

2020 ◽

Vol 10 (9) ◽

pp. e037113

Author(s):

Kotaro Sato ◽

Ryoko Michinobu ◽

Tesshu Kusaba

Keyword(s):

Primary Care ◽

Mixed Methods ◽

Family Medicine ◽

Phase I ◽

Phase Ii ◽

Medical Specialty ◽

Structured Interviews ◽

Two Phase ◽

Care Systems

IntroductionFamily physicians or general practitioners play central roles in many countries’ primary care systems, but family medicine (FM) remains relatively unestablished in Japan. Previous studies in Japan have examined the general population’s understanding of FM as a medical specialty, but none have explored this topic using actual FM clinic patients. Here, we describe a protocol to explore the perceptions of FM among long-term patients of one of Japan’s oldest FM clinics.Methods and analysisThe study will be conducted at the Motowanishi Family Clinic in Hokkaido, Japan, using patients who have attended the clinic for over 10 years. The analysis will adopt a two-phase explanatory sequential mixed methods design. During phase I, quantitative data from participants’ medical records will be collected and reviewed, and patients’ perceptions of FM will be assessed through a questionnaire. The correlations between participants’ knowledge that the clinic specialises in FM and various characteristics will be examined. In phase II, qualitative data will be collected through semi-structured interviews of approximately 10 participants selected using maximum variation sampling based on phase I results. A thematic analysis will be conducted in phase II to identify patients’ perceptions and changes in perceptions. Finally, each theme identified in phase II will be transformed into a quantitative variable to analyse the relationships between the phases. A joint display will be used to integrate the phases’ findings and examine how phase II results explain phase I results.Ethics and disseminationThe institutional review board of the Japan Primary Care Association has approved this research (2019-003). The results will be presented at the association’s annual academic meeting and submitted for publication in relevant journals. The findings will also be provided to the patients via the clinic’s internal newsletter.

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COVID-19 and radiation oncology: the experience of a two-phase plan within a single institution in central Italy

Radiation Oncology ◽

10.1186/s13014-020-01670-9 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Luciana Caravatta ◽

Consuelo Rosa ◽

Maria Bernadette Di Sciascio ◽

Andrea Tavella Scaringi ◽

Angelo Di Pilla ◽

...

Keyword(s):

Phase I ◽

Phase Ii ◽

Central Italy ◽

Significant Risk ◽

Tumor Board ◽

Radiotherapy Planning ◽

Two Phase ◽

Hospital Environments ◽

Two Phases

Abstract Background COVID-19 in Italy has led to the need to reorganize hospital protocols with a significant risk of interruption to cancer treatment programs. In this report, we will focus on a management model covering the two phases of the COVID-19 emergency, namely lockdown-phase I and post-lockdown-phase II. Methods The following steps were taken in the two phases: workload during visits and radiotherapy planning, use of dedicated routes, measures for triage areas, management of suspected and positive COVID-19 cases, personal protective equipment, hospital environments and intra-institutional meetings and tumor board management. Due to the guidelines set out by the Ministry of Health, oncological follow-up visits were interrupted during the lockdown-phase I; consequently, we set about contacting patients by telephone, with laboratory and instrumental exams being viewed via telematics. During the post-lockdown-phase II, the oncological follow-up clinic reopened, with two shifts operating daily. Results By comparing our radiotherapy activity from March 9 to May 4 2019 with the same period in 2020 during full phase I of the COVID-19 emergency, similar results were achieved. First radiotherapy visits, Simulation Computed Tomography and Linear Accelerator treatments amounted to 123, 137 and 151 in 2019 compared with 121, 135 and 170 in 2020 respectively. There were no cases of COVID-19 positivity recorded either in patients or in healthcare professionals, who were all negative to the swab tests performed. Conclusion During both phases of the COVID-19 emergency, the planned model used in our own experience guaranteed both continuity in radiotherapy treatments whilst neither reducing workload nor interrupting treatment and, as such, it ensured the safety of cancer patients, hospital environments and staff.

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Combination of Oxaliplatin Plus Irinotecan in Patients With Gastrointestinal Tumors: Results of Two Independent Phase I Studies With Pharmacokinetics

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.6.1751 ◽

1999 ◽

Vol 17 (6) ◽

pp. 1751-1751 ◽

Cited By ~ 94

Author(s):

Ernesto Wasserman ◽

Caroline Cuvier ◽

François Lokiec ◽

François Goldwasser ◽

Salima Kalla ◽

...

Keyword(s):

Phase I ◽

Phase Ii ◽

Performance Status ◽

Maximum Tolerated Dose ◽

Two Phase ◽

Phase I Studies ◽

Phase Ii Studies ◽

Minute Period ◽

Grade 3 ◽

Febrile Episodes

PURPOSE: Two phase I studies of the oxaliplatin and irinotecan combination were performed in advanced gastrointestinal cancer patients to characterize the safety and pharmacokinetics of the regimen. PATIENTS AND METHODS: Patients with a performance status (PS) of ≤2 and normal hematologic, hepatic, and renal functions received oxaliplatin (2-hour intravenous infusion) followed 1 hour later by irinotecan administered over a 30-minute period, every 3 weeks. Dose levels that were explored ranged from 85 to 110 mg/m2 for oxaliplatin and 150 to 250 mg/m2 for irinotecan. Plasma pharmacokinetics of total and ultrafiltrable platinum, irinotecan, SN-38, and its glucuronide, SN-38G, were determined. RESULTS: Thirty-nine patients with gastrointestinal carcinomas (24 with colorectal cancer [CRC], four with pancreas cancer, four with gastric cancer, three with hepatocarcinoma, and four with other) received 216 treatment cycles. Median age was 54 years (range, 21 to 72 years); 95% had PS of 0 to 1; all but six had failed fluorouracil (5-FU) chemotherapy. The maximum-tolerated dose was oxaliplatin 110 mg/m2 plus irinotecan 200 mg/m2 in one study and oxaliplatin 110 mg/m2 plus irinotecan 250 mg/m2 in the other study. Grade 3 to 4 diarrhea and febrile neutropenia were dose-limiting toxicities; other toxicities included emesis and dose-cumulative neuropathy. Recommended dose for phase II studies is oxaliplatin 85 mg/m2 and irinotecan 200 mg/m2. At this dose (12 patients, 65 cycles), grade 3 and 4 toxicities per patient included the following: emesis in 42% of patients, neutropenia in 33% (febrile episodes in 17%), peripheral neuropathy in 25%, delayed diarrhea in 17%, and thrombocytopenia in 8%. Two patients with Gilbert's syndrome experienced severe irinotecan toxicity. No plasmatic pharmacokinetic interactions were detected. Seven partial responses were observed in 24 CRC patients. CONCLUSION: This combination is feasible, with activity in 5-FU–resistant CRC patients. Phase I studies that explore the every-2-weeks schedule, in addition to phase II studies of this schedule (as well as in combination with 5-FU) as second-line therapy of metastatic CRC, are ongoing.

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‘I actually felt like I was a researcher myself.’ On involving children in the analysis of qualitative paediatric research in the Netherlands

BMJ Open ◽

10.1136/bmjopen-2019-034433 ◽

2020 ◽

Vol 10 (8) ◽

pp. e034433

Author(s):

Malou L Luchtenberg ◽

Els L M Maeckelberghe ◽

AA Eduard Verhagen

Keyword(s):

The Netherlands ◽

Phase I ◽

Phase Ii ◽

Qualitative Data ◽

Paediatric Research ◽

Two Phase ◽

New Approach ◽

Time Investment ◽

Framework Approach ◽

Group Meetings

ObjectivesTo evaluate the feasibility of a new approach to paediatric research whereby we involved children in analysing qualitative data, and to reflect on the involvement process.SettingThis was a single-centre, qualitative study in the Netherlands. It consisted of research meetings with individual children at home (Phase I) or group meetings at school (Phase II). In Phase I, we identified themes from a video interview during five one-on-one meetings between a child co-researcher and the adult researcher. In Phase II, during two group meetings, we explored the themes in detail using fragments from 16 interviews.ParticipantsWe involved 14 school children (aged 10 to 14 years) as co-researchers to analyse children’s interviews about their experience while participating in medical research. Notes were taken, and children provided feedback. A thematic analysis was performed using a framework approach.ResultsAll co-researchers identified themes. The time needed to complete the task varied, as did the extent to which the meetings needed to be structured to improve concentration. The children rated time investment as adequate and they considered acting as co-researcher interesting and fun, adding that they had learnt new skills and gained new knowledge. The experience also led them to reflect on health matters in their own lives. The adult researchers considered the process relatively time intensive, but the project did result in a more critical assessment of their own work.ConclusionThe new, two-phase approach of involving children to help analyse qualitative data is a feasible research method. The novelty lies in involving children to help identify themes from original interview data, thereby limiting preselection of data by adults, before exploring these themes in detail. Videos make it easier for children to understand the data and to empathise with the interviewees, and limits time investment.

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