Protocol Development in Clinical Trials for Healthcare Management

Author(s):  
Swati Changdeo Jagdale ◽  
Asawaree Anand Hable ◽  
Anuruddha R. Chabukswar

Clinical trial is a part of clinical research. It is a systematic experimental biomedical study. They are carried out to evaluate the effectiveness and safety of medications or medical devices or biologics. Trials are conducted to check safety and efficacy of new drug. It includes four phases as phase I, II, III, and IV. The study is carried out according to study protocol and standard operating procedures as per good clinical practices guidelines. The study protocol is developed by the researchers and approved by an independent committee called as Institutional Review Board. Protocol is a roadmap for team of healthcare professionals involved in investigation work. It should explain the significance of research trial, location, detail procedure, methods, activities, time allotment, financial estimate and any other information required. The content of protocol are title, objective, background, eligibility criteria, study methodology, risks or adverse effects, benefits, alternative treatment, data collection, statistical treatment, regulatory guidance, and other information.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8531-8531
Author(s):  
Mariano Provencio ◽  
Delvys Rodriguez-Abreu ◽  
Ana Collazo Lorduy ◽  
Gloria Mª Serrano ◽  
Ana Laura Ortega Granados ◽  
...  

8531 Background: Coronavirus disease 2019 (COVID-19) is diagnosed by detecting the virus by reverse transcription polymerase chain reaction (RT-PCR). The majority of p go on to develop antibodies (Ab) against viral proteins. However, it is not known how long these antibodies last nor whether cancer treatments could affect the duration of immune response. The prognosis and greater or lesser vulnerability of the oncological population are also unknown. Methods: This prospective, longitudinal, multicenter serological study in the setting of SARS-CoV-2 was carried out in 50 Spanish hospitals. Eligibility criteria was a diagnosis of any thoracic cancer. The first determinations were performed between April 21, 2020 and June 3, 2020, either for p in follow up or in active treatment. Between September 10, 2020, and November 20, 2020, the second antibody (Ab) determination was performed in all previously seropositive p. Clinical and treatment data were collected, as was their clinical situation at study end. Study objectives were to prospectively determine seroprevalence in unselected lung cancer p during the first wave of the pandemic; the natural history of these p; the persistence of immunity more than 4 months after first determination; protection or lack thereof against reinfection after this period, and the nature of such protection; and the influence of treatments on maintenance or loss of immunity. Results: Of 1,500 p studied, 128 were seropositive, representing an overall prevalence of 8.5% seropositivity [95% confidence interval [CI], 7.2%, 10.1%]. Seventy-five percent were in active cancer treatment. COVID-19 infection was suspected in 47.7% [95% CI, 38.8%, 56.6%]. A second determination was performed on average 4.5 months later [IQR: 4; 5] and obtained for 104 of the initially seropositive p (81%). A second determination could not be obtained in 24 p, the majority due to death caused by disease progression (73%). In the second determination, IgG was not detected in 30.8% (32/104) of p. The severity of the infection, the need for hospitalization (p: 0.032) and the presence of symptoms at diagnosis (p: 0.02), including fever (p: 0.005) and nasal congestion (p: 0.005), were associated with persistence of immunity in the second determination. No variables or treatments received were associated with Ab loss. At time of last follow-up among those p for whom a second determination was performed, 89% (93 p) had completely recovered from the virus, with no lasting after effects. Only 1 of the 128 (0.78%) seropositive p had died from COVID-19. Conclusions: The prevalence of infection in lung cancer p is similar to that of the general population. Immunity against SARS-CoV-2 does not appear to be compromised by treatment, persisting beyond 4 months. Neither do mortality rates appear to be particularly high in this unselected population.


2015 ◽  
Vol 2015 ◽  
pp. 1-6
Author(s):  
Jimin Park ◽  
Hyun Soo Kim ◽  
Seung Min Lee ◽  
Kanghyun Yoon ◽  
Woo-shik Kim ◽  
...  

Background.Atrial fibrillation (AF) is the most common form of arrhythmia. Several trials have suggested that acupuncture may prevent AF. However, the efficacy of acupuncture for AF prevention has not been well investigated. Therefore, we designed a prospective, two-parallel-armed, participant and assessor blinded, randomized, sham-controlled clinical trial to investigate acupuncture in persistent AF (ACU-AF).Methods.A total of 80 participants will be randomly assigned to active acupuncture or sham acupuncture groups in a 1 : 1 ratio. Both groups will take the same antiarrhythmic medication during the study period. Patients will receive 10 sessions of acupuncture treatment once a week for 10 weeks. The primary endpoint is AF recurrence rate. Secondary endpoints are left atrium (LA) and left atrial appendage (LAA) changes in function and volume, and inflammatory biomarker changes.Ethics.This study protocol was approved by the institutional review boards (IRBs) of Kyung Hee University Hospital (number 1335-04). This trial is registered with clinicaltrials.govNCT02110537.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7084-7084
Author(s):  
Cristina Merkhofer ◽  
Shasank Chennupati ◽  
Qin Sun ◽  
Keith D. Eaton ◽  
Renato G. Martins ◽  
...  

7084 Background: To assess the value of CTs in advanced NSCLC from the payer perspective, we compared insurance-related total direct medical costs for NSCLC patients who enrolled in CTs vs. those who did not. Methods: After linking electronic health records with tumor registry and claims data, we identified 101 patients with metastatic NSCLC diagnosed between 1/1/2007 and 12/31/2015 and treated at the Seattle Cancer Care Alliance. Eligibility criteria included 60-day minimum survival, claims for ≥ 1 anti-cancer drug within 180 days of diagnosis and insurance enrollment for the first 12 months after diagnosis. We abstracted patient sociodemographic, disease and treatment data, and obtained death dates from the Washington State Cancer Registry, censoring patients alive on 3/7/2019.We used the Kaplan-Meier sample-average (KMSA) estimator with bootstrapped 95% confidence intervals to describe direct medical costs and compared costs in CT enrollees vs. non-enrollees by applying a generalized linear model (Gamma distribution, log link) adjusted for confounding covariates. Results: Of 101 patients, 39 (39%) enrolled in CTs. Compared with non-enrollees, CT enrollees were younger (mean age 61.6 vs. 66.5 years), female (67% vs. 47%), Asian (18% vs. 11%), never smokers (41% vs.32%), had commercial insurance (44% vs. 35%), resided in metropolitan areas (90% vs. 79%) and had a higher median income ($81,149 vs. $76,844). Table shows KMSA estimates of total direct medical costs and adjusted mean lifetime total direct medical costs by CT participation. After adjusting for sex, smoking status, residence, income, insurance payer, ECOG and mutation status, CT enrollment was associated with an increase in lifetime total direct medical costs compared with no enrollment (adjusted cost ratio=1.39; 95% CI: 1.01, 1.90; p=0.043). Conclusions: CT participation is associated with increased total direct medical costs in patients with metastatic NSCLC. Our results may inform partnerships between trial sponsors, oncology centers and payers to sustain treatment innovation through CTs. [Table: see text]


Author(s):  
F Zarei ◽  
B Zeinali-Rafsanjani

Rationale and Objective: The objective of this study is to evaluate the methodological adherence of diagnostic accuracy studies published in radiology journals, which were indexed in different databases with the STARD standard guide 2015.Materials and Methods: The different databases were searched in order to find suitable journals. Among 84 English radiology journals, 31 journal were selected randomly. In order to find the articles, the same search fields and search terms were used. All the items of STARD checklist 2015 were considered to take in to account in assessment of the adherence of the articles to the standard. Total STARD score for each article was calculated by summing the number of reported items.Results: 151 articles from 31 journals were evaluated to check the adherence of their structure to STARD standard. Based on the results the articles had the most adherence with the STARD standard in material and method part the item of participants, discussion section, and title or abstract. On the contrary, most of the articles were not adhere to other information which are new items in STARD 2015. Among radiology diagnostic accuracy articles only one article (0.66%) had a registration number and 10 (6.62%) articles had a link to full study protocol. More than 60% of articles adhered to the ethics (69.54%) and source of support (63.58%).Conclusions: The radiology diagnostic accuracy studies were adhered to 69.45% STARD items, which shows an improvement in reporting the diagnostic accuracy articles in comparison to previous studies.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
William J. Cragg ◽  
Kathryn McMahon ◽  
Jamie B. Oughton ◽  
Rachel Sigsworth ◽  
Christopher Taylor ◽  
...  

Abstract Background Eligibility criteria are a fundamental element of clinical trial design, defining who can and who should not participate in a trial. Problems with the design or application of criteria are known to occur and pose risks to participants’ safety and trial integrity, sometimes also negatively impacting on trial recruitment and generalisability. We conducted a short, exploratory survey to gather evidence on UK recruiters’ experiences interpreting and applying eligibility criteria and their views on how criteria are communicated and developed. Methods Our survey included topics informed by a wider programme of work at the Clinical Trials Research Unit, University of Leeds, on assuring eligibility criteria quality. Respondents were asked to answer based on all their trial experience, not only on experiences with our trials. The survey was disseminated to recruiters collaborating on trials run at our trials unit, and via other mailing lists and social media. The quantitative responses were descriptively analysed, with inductive analysis of free-text responses to identify themes. Results A total of 823 eligible respondents participated. In total, 79% of respondents reported finding problems with eligibility criteria in some trials, and 9% in most trials. The main themes in the types of problems experienced were criteria clarity (67% of comments), feasibility (34%), and suitability (14%). In total, 27% of those reporting some level of problem said these problems had led to patients being incorrectly included in trials; 40% said they had led to incorrect exclusions. Most respondents (56%) reported accessing eligibility criteria mainly in the trial protocol. Most respondents (74%) supported the idea of recruiter review of eligibility criteria earlier in the protocol development process. Conclusions Our survey corroborates other evidence about the existence of suboptimal trial eligibility criteria. Problems with clarity were the most often reported, but the number of comments on feasibility and suitability suggest some recruiters feel eligibility criteria and associated assessments can hinder recruitment to trials. Our proposal for more recruiter involvement in protocol development has strong support and some potential benefits, but questions remain about how best to implement this. We invite other trialists to consider our other suggestions for how to assure quality in trial eligibility criteria.


BMJ Open ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. e024473 ◽  
Author(s):  
Wendy Rogers ◽  
Matthew P Robertson ◽  
Angela Ballantyne ◽  
Brette Blakely ◽  
Ruby Catsanos ◽  
...  

ObjectivesThe objective of this study is to investigate whether papers reporting research on Chinese transplant recipients comply with international professional standards aimed at excluding publication of research that: (1) involves any biological material from executed prisoners; (2) lacks Institutional Review Board (IRB) approval and (3) lacks consent of donors.DesignScoping review based on Arksey and O’Mallee’s methodological framework.Data sourcesMedline, Scopus and Embase were searched from January 2000 to April 2017.Eligibility criteriaWe included research papers published in peer-reviewed English-language journals reporting on outcomes of research involving recipients of transplanted hearts, livers or lungs in mainland China.Data extraction and synthesisData were extracted by individual authors working independently following training and benchmarking. Descriptive statistics were compiled using Excel.Results445 included studies reported on outcomes of 85 477 transplants. 412 (92.5%) failed to report whether or not organs were sourced from executed prisoners; and 439 (99%) failed to report that organ sources gave consent for transplantation. In contrast, 324 (73%) reported approval from an IRB. Of the papers claiming that no prisoners’ organs were involved in the transplants, 19 of them involved 2688 transplants that took place prior to 2010, when there was no volunteer donor programme in China.DiscussionThe transplant research community has failed to implement ethical standards banning publication of research using material from executed prisoners. As a result, a large body of unethical research now exists, raising issues of complicity and moral hazard to the extent that the transplant community uses and benefits from the results of this research. We call for retraction of this literature pending investigation of individual papers.


2021 ◽  
Author(s):  
Paul Mehta ◽  
Jaime Raymond ◽  
Moon Kwon Han ◽  
Theodore Larson ◽  
James D Berry ◽  
...  

BACKGROUND Researchers face challenges in patient recruitment, especially for rare, fatal diseases like ALS. These challenges include obtaining sufficient statistical power as well as meeting eligibility requirements such as age, sex, and study proximity. Similarly, persons with ALS (PALS) face difficulty finding and enrolling in research studies for which they are eligible. OBJECTIVE To describe how the federal Agency for Toxic Substances and Disease Registry’s (ATSDR) National ALS Registry is linking PALS to scientists who are conducting research, clinical trials, and epidemiological studies. METHODS Through the Registry’s online Research Notification Mechanism, PALS can elect to be notified about new research opportunities. This mechanism allows researchers to upload a standardized application outlining their study design and objectives, and proof of Institutional Review Board (IRB) approval. If the application is approved, ATSDR queries the Registry for PALS meeting the study’s specific eligibility criteria, and then distributes the researcher’s study material and contact information to PALS via email. PALS then need to contact the researcher directly to take part in any research. Such an approach allows ATSDR to protect the confidentiality of Registry enrollees. RESULTS From 2013 – 2019, a total of 46 institutions around the US. have leveraged this tool and over 600,000 emails have been sent resulting conservatively in over 2,000 patients recruited for clinical trials and epidemiological studies. CONCLUSIONS The National ALS Registry’s Research Notification Mechanism benefits PALS by connecting them to appropriate ALS research. Simultaneously, the system benefits researchers by expediting recruitment, increasing sample size, and efficiently identifying PALS meeting specific eligibility requirements. As more researchers learn about and use this mechanism, both PALS and researchers can hasten research and expand trial options for PALS.


2018 ◽  
Vol 616 ◽  
pp. A9 ◽  
Author(s):  
X. Luri ◽  
A. G. A. Brown ◽  
L. M. Sarro ◽  
F. Arenou ◽  
C. A. L. Bailer-Jones ◽  
...  

Context. The second Gaia data release (Gaia DR2) provides precise five-parameter astrometric data (positions, proper motions, and parallaxes) for an unprecedented number of sources (more than 1.3 billion, mostly stars). This new wealth of data will enable the undertaking of statistical analysis of many astrophysical problems that were previously infeasible for lack of reliable astrometry, and in particular because of the lack of parallaxes. However, the use of this wealth of astrometric data comes with a specific challenge: how can the astrophysical parameters of interest be properly inferred from these data? Aims. The main focus of this paper, but not the only focus, is the issue of the estimation of distances from parallaxes, possibly combined with other information. We start with a critical review of the methods traditionally used to obtain distances from parallaxes and their shortcomings. Then we provide guidelines on how to use parallaxes more efficiently to estimate distances by using Bayesian methods. In particular we also show that negative parallaxes, or parallaxes with relatively large uncertainties still contain valuable information. Finally, we provide examples that show more generally how to use astrometric data for parameter estimation, including the combination of proper motions and parallaxes and the handling of covariances in the uncertainties. Methods. The paper contains examples based on simulated Gaia data to illustrate the problems and the solutions proposed. Furthermore, the developments and methods proposed in the paper are linked to a set of tutorials included in the Gaia archive documentation that provide practical examples and a good starting point for the application of the recommendations to actual problems. In all cases the source code for the analysis methods is provided. Results. Our main recommendation is to always treat the derivation of (astro-)physical parameters from astrometric data, in particular when parallaxes are involved, as an inference problem which should preferably be handled with a full Bayesian approach. Conclusions. Gaia will provide fundamental data for many fields of astronomy. Further data releases will provide more data, and more precise data. Nevertheless, to fully use the potential it will always be necessary to pay careful attention to the statistical treatment of parallaxes and proper motions. The purpose of this paper is to help astronomers find the correct approach.


2008 ◽  
Vol 36 (2) ◽  
pp. 352-355 ◽  
Author(s):  
Moira A. Keane

With rapidly expanding technological capacity, research has outpaced the existing infrastructure of ethical and regulatory guidance. In the area of incidental findings (IFs), this is particularly true.The regulations under which most Institutional Review Boards (IRBs) operate were established over 25 years ago and have not been substantially altered in the intervening years. The technology available today that creates the opportunity for IFs was not conceived of, or considered, in the crafting of those regulations. Therefore, little guidance can be derived directly from these regulations. Rather, aspects of existing ethical guidance and regulations can be adapted to assist IRBs and researchers in dealing with issues surrounding IFs.


BMJ Open ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. e034869
Author(s):  
Cornelia Betsch ◽  
Katrine Bach Habersaat ◽  
Sergei Deshevoi ◽  
Dorothee Heinemeier ◽  
Nikolay Briko ◽  
...  

IntroductionPublished in 2018, the 5C scale is psychometrically validated to assess five psychological antecedents of vaccination (confidence, complacency, constraints, calculation and collective responsibility). The original version offers a validated English and German scale to assess these determinants with a short 5-item scale (1 item per antecedent) and a long 15-item scale (3 items per antecedent). This sample study protocol provides a step-by-step guidance for the process of adapting the 5C scale to another country, language or cultural context. Data obtained from the 5C scale can support developing, implementing and evaluating an intervention and monitoring of general vaccine acceptance and demand.Methods and analysisPhase 1 comprises the adaptation of the 5C scale including the translation and back translation of the antecedents, an expert evaluation of the antecedents and the identification of new antecedents as well as a pretest. Phase 2 involves the validation of the translated and potentially expanded scale including the assessment of reliability, construct and concurrent validity of all items of the scale. Code for data analysis is provided.Ethics and disseminationThe University of Erfurt’s institutional review board provided ethical clearance (EV-201900416.2). The authors suggest and encourage publicly sharing all data obtained from the translated 5C scale (eg, on publication). The materials and the code for data analysis to support the process described in this protocol are available inhttps://osf.io/2agxe/. Sharing data on vaccine acceptance and demand is in the public and the scientific interest and will facilitate gaining a global overview of its current state and development over time. The authors of the original 5C scale are currently working on an online platform to facilitate publishing the data and to visualise the psychological antecedents across different countries.


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