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Prescribing doctors are, increasingly, using clinical trial data as a major source of information for evidence-based medicine for the treatment of infectious diseases, as in other clinical disciplines. However, it may be difficult to extract from these data the information that is needed for the management of the individual patient. At the same time, clinical trial data have been used, apparently satisfactorily, in the process of drug registration, and the pharmaceutical industry has spent increasingly large sums of money to satisfy the needs of this process. This paradox— more money spent, but an outcome of limited usefulness to the prescriber—was the subject of the report of a group with expertise in all aspects of antibiotic clinical trials, meeting as the Witley Park Symposium. 1 Their objective was to identify the strengths and weaknesses of the current antibiotic clinical trial procedure for all its potential users, and to suggest means that would improve the utility of the results for doctors and their individual patients. The group identified current users of clinical trial data as: the pharmaceutical company developing, promoting and marketing the drug; the regulatory agencies responsible for drug registration for marketing; a group, defined as politicians, responsible for the well-being of the public; prescribers; and patients, who are taking an increasingly vociferous interest in the way in which their illnesses are managed. From this list alone it is clear that the needs are diverse, and that not all data are of value to all users. The established validity of the comparative, randomized, blinded, prospective clinical trial, with its means of avoiding bias and its statistically valid outcome, was fully recognized. It was also recognized that its full potential was not always realized in practice. A major disadvantage of such trials was identified as their reliance on historical results that established the efficacy of what is usually referred to as the comparator drug: this drug may never have been satisfactorily demonstrated to be effective in comparison with placebo, and may, furthermore, have lost efficacy because of an increasing incidence of acquired resistance. As a result of the common requirement for the demonstration of equivalent efficacy, patients infected with bacteria that are resistant in vitro are often excluded from clinical trials, so that the clinician will have no guidance on how to manage such infections, and the microbiologist no guidance on the clinical importance of the antimicrobial resistance that he recognizes in the laboratory. There is an added problem that antibiotics have to be prescribed for serious infection before the specific pathogen has been identified: even in the best designed clinical trial, patients are treated for, e.g., community-acquired pneumonia, rather than for pneumococcal pnuemonia, let alone penicillin-resistant pneumococcal pneumonia. At the very least this will result in randomization problems when subsets of patients are eventually analysed. The conclusion of the Witley Park group was that these and other factors result in failures in external validity—that is, the results cannot be applied to individual patients who rarely correspond to the ‘average’ patient for whom results are necessarily presented in such trials. This is the nub of the problem for the would-be rational antibiotic prescriber. The problem was not left there. The group recognized that rare, adverse effects on the individual patient would not necessarily be recognized, even in the large clinical trials that appear to have become the norm. Furthermore, the effects of prescribing a given drug on the environment and on society at large, whether this is an increase in antibiotic resistance or the cost burden, are scarcely considered at all in clinical trials. Finally, little use is made of the extensive databases of medically relevant data that are becoming generally available. 2 In the face of all these problems, changes in the way antibiotic clinical trials are designed and performed are clearly necessary, although this must not tip the balance so far as to render them less useful for those who currently derive greatest benefit from them. In coming up with sug
3Treating the Black Hypertensive in 2010: Achieve Lower Targets While Awaiting More Definitive Evidence
Treating the Black Hypertensive in 2010: Achieve Lower Targets While Awaiting More Definitive Evidence
8Prospective Clinical Trial Registration: A Prerequisite for Publishing Your Results.
Prospective Clinical Trial Registration: A Prerequisite for Publishing Your Results.
15The impact of evidence from clinical trials on counselling for over‐the‐counter drugs: A national survey of pharmaceutical staff in German pharmacies
Evidence from clinical trials should form the foundation of healthcare advice. Comparatively little has been investigated about the implementation of evidence in over-the-counter (OTC) counselling in community pharmacies. The objective of this study was to explore the current impact of clinical trials on OTC counselling from the perspective of pharmaceutical staff. Pharmaceutical staff in German community pharmacies were invited to participate in a nationwide cross-sectional survey using SoSci Survey. Within the questionnaire, the following items were queried: (i) attitudes towards influencing factors on OTC drug recommendation, (ii) practical procedure of OTC drug recommendations, (iii) experiences and challenges in handling clinical trials, and (iv) current and desired continuing education on self-medication. Multiple logistic regression was employed to identify predictors for OTC recommendations based on clinical trials in routine. In total, 1068 participants completed the survey. (i) Clinical trial data were rated as 'very important' for drug recommendations by 33% and as 'rather important' by 50%. (ii) 8% reported that they base their recommendations on clinical trial data 'in almost all consultations', 40% 'in most consultations'. (iii) 69% faced difficulties in including clinical trial data into their counselling. (iv) 7% read original clinical trials at least once a month. Predictors for routine OTC recommendations based on clinical trials were as follows: male gender, university degree, clinical trials considered to be important for recommendations, inclusion of clinical trials in counselling assessed as easy, higher frequency of reading specialized literature per year, increasing number of working pharmacists in the pharmacy, and more casual than regular customers in the pharmacy. Most of the pharmaceutical staff recognize the importance of clinical studies for self-medication advice. Based on self-report, however, clinical trial data are not taken routinely into account in practice. Only a minor proportion of staff routinely deal with studies. Therefore, appropriate instruments are required to make knowledge from clinical trials available in community pharmacies.
Read more26Clinical Trial Methodology
Now viewed as its own scientific discipline, clinical trial methodology encompasses the methods required for the protection of participants in a clinical trial and the methods necessary to provide a valid inference about the objective of the trial. Drawing from the authors' courses on the subject as well as the first author's more than 30 years wor
Read more146British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy.
British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy.
6Background and rationale for mechanism of action, efficacy, and safety of fingolimod (Gilenya), the first oral therapy for remitting-relapsing multiple sclerosis
Background and rationale for mechanism of action, efficacy, and safety of fingolimod (Gilenya), the first oral therapy for remitting-relapsing multiple sclerosis
Read moreSynthetic control arms and other uses of external data in clinical trials for hematological malignancies.
Synthetic control arms and other uses of external data in clinical trials for hematological malignancies.
12Sharing Clinical Trial Data: A Proposal from the International Committee of Medical Journal Editors
Sharing Clinical Trial Data: A Proposal from the International Committee of Medical Journal Editors
68Radiation therapy quality assurance in clinical trials – Global harmonisation group
Radiation therapy quality assurance in clinical trials – Global harmonisation group
197Smoking, The Missing Drug Interaction in Clinical Trials: Ignoring the Obvious
Tobacco use is universally recognized as the foremost preventable cause of cancer in the United States and globally and is responsible for 30% of all cancer-related deaths in the United States. Tobacco use, including exposure to secondhand smoke has been implicated as a causal or contributory agent in an ever-expanding list of cancers, including lung, oral cavity and pharynx, pancreas, liver, kidney, ureter, urinary bladder, uterine cervix, and myeloid leukemia. In addition to and independent of the etiologic effects of tobacco carcinogens in numerous cancers, there is a growing literature on the direct and indirect effects of smoking on treatment efficacy (short-term and long-term outcomes), toxicity and morbidity, quality of life (QOL), recurrence, second primary tumors (SPT), and survival time as summarized below. Oncology health professionals have called for increased advocacy for tobacco control. Despite the critical relevance of smoking to cancer outcomes, most oncology clinical trials do not collect data on smoking history and status unless the malignancy is widely acknowledged as smoking related (e.g., lung or head and neck cancer). Usually, these data are collected only at trial registration. Changes in smoking status during treatment or follow-up are monitored in very few trials and are infrequently reported in sample descriptions or included in analysis plans as a potential moderator of outcomes. Based on mounting evidence that tobacco use affects cancer treatment outcomes and survival, we recommend that smoking history and status be systematically collected as core data in all oncology clinical trials: at diagnosis, at trial registration, and throughout treatment and follow-up to long-term survival or death. We feel that the inclusion and analysis of such data in clinical trials will add important information to the interpretation of outcomes and the development of scientific knowledge in this area. Smoking status has been called another "vital sign" because of its relevance to a patient's immediate medical condition. We explain the critical value of knowing the smoking status of every patient with cancer at every visit by providing a brief overview of the following research findings: (a) the effects of tobacco use on cancer treatment and outcome; (b) recent findings on the role of nicotine in malignant processes; (c) some unexpected results concerning tobacco status, treatment, and disease outcome; and (d) identifying key questions that remain to be addressed. We provide a suggested set of items for inclusion in clinical trial data sets that also are useful in clinical practice.
Read more1Abstract IA08: Clinical trial design and master protocols in NCI clinical treatment trials.
Cancer medicine continues to evolve into a more molecularly based discipline with many new treatments being developed aimed at specific cancer-related pathways and genetic alterations. In order to meet the challenges of the evolving science, new clinical trial designs and approaches for treatment trials are needed to evaluate the promise of these potential therapies. The National Cancer Institute (NCI) with the national NCI Clinical Trials Network (NCTN) Groups will launch two clinical research initiatives in lung cancer in 2014 that demonstrate innovative approaches to the design and conduct of clinical trials. The first initiative is the ALCHEMIST trial (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial) which is aimed at patients with lung adenocarcinoma that has been entirely removed by surgery. In this study, samples of tumor tissue from thousands of patients will be tested for two specific genetic alterations, one in the EGFR gene, and the other in the ALK gene. These alterations are not common; about 10% of the lung cancer patient population in the US will have tumors with alterations in the EGFR gene and 5% will have alterations in the ALK gene. Rather than conduct a single trial for each alteration, the screening component of the ALCHEMIST trial will screen patients for both alterations at the same time. The ALCHEMIST is connected to 2 specific NCI-supported NCTN Group clinical treatment trials that are each testing a targeted agent specific for one of the alterations in conjunction with adjuvant therapy. Patients found to have tumors containing one of the alterations will be offered enrollment onto the appropriate clinical treatment trial. Every patient in the ALCHEMIST trial, including those without an EGFR or ALK alteration, will also be studied for cancer risk characteristics and their tumor tissue will be analyzed in a research genomics initiative conducted by the NCI Center for Cancer Genomics (CCG). This effort will employ next-generation sequencing technology to capitalize on the foundation of the CCG's earlier effort, the Cancer Genome Atlas. The second initiative, the Advanced Squamous Cell Carcinoma Lung Master Protocol, is a public-private effort made possible through collaboration with stakeholders including the NCI, NCTN Groups, FDA, NIH Foundation, the Friends of Cancer patient advocacy group, and the pharmaceutical industry. By pooling resources to screen tumor samples from about a thousand patients per year with advanced squamous cell carcinoma for multiple genetic alterations, this master protocol will enable several, randomized, phase II clinical trials with promising new agents to take place in parallel within a single study management framework. Agents will be evaluated rapidly and either be further evaluated in a phase III clinical trial or replaced by other new agents for phase II evaluation, without having to develop individual trials de novo each time. Compared with the usual process of developing clinical trials, these two new design approaches will hopefully allow more patients to be enrolled in trials with agents targeted for important molecular characteristics specific for their tumors and the trials will yield clinically useful results more rapidly. Citation Format: Margaret M. Mooney, Jack Welch, Jeffrey S. Abrams. Clinical trial design and master protocols in NCI clinical treatment trials. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr IA08.
Read moreEnhancing Gen3 for clinical trial time series analytics and data discovery: a data commons framework for NIH clinical trials
This work presents a framework for enhancing Gen3, an open-source data commons platform, with temporal visualization capabilities for clinical trial research. We describe the technical implementation of cloud-native architecture and integrated visualization tools that enable standardized analytics for longitudinal clinical trial data while adhering to FAIR principles. The enhancement includes Kubernetes-based container orchestration, Kibana-based temporal analytics, and automated ETL pipelines for data harmonization. Technical validation demonstrates reliable handling of varied time-based data structures, while maintaining temporal precision and measurement context. The framework's implementation in NIH HEAL Initiative networks studying chronic pain and substance use disorders showcases its utility for real-time monitoring of longitudinal outcomes across multiple trials. This adaptation provides a model for research networks seeking to enhance their data commons capabilities while ensuring findable, accessible, interoperable, and reusable clinical trial data.
Read more12Using GFR, Albuminuria, and Their Changes in Clinical Trials and Clinical Care
Using GFR, Albuminuria, and Their Changes in Clinical Trials and Clinical Care
5Comments on Progress, Medical Care, and the Overuse of Technology
Comments on Progress, Medical Care, and the Overuse of Technology
PhaseForward: Web-based vs. Web-enabled Clinical Trial Solutions
and biotechnology industry is rushing to embrace the Internet as a powerful method of collecting clinical trial data. Most clinical trials today still use a paper-based management system, which is time-consuming and error-prone. Over the last 20 several million dollars. Once the data is collected, it must be entered into a database and time taken to “clean” the data before the trial is unblinded and analyzed. The effect of this delay is costly. The advantages of the Internet in the management of clinical trial data are substantial, providing significant improvements in the quality and timeliness of data collection in clinical trials. Internet clinical trials can give clinical trial sponsors real-time access to data, eliminating an extremely inefficient process of logging, tracking, entering, and reconciliation of clinical trial data. The Internet centralizes data, making it immediately available to those who must review and approve it. Through the Internet, the clinical trial process can become more efficient and fulfill the increasing demand for higher throughput by pharmaceutical companies. To meet this demand, some web developers are producing “web-enabled” versions of clinical trial software, rather than developing truly “web-based” solutions. The difference shows up in performance, maintenance, accessibility, economy, and security. The performance of a carefully constructed web-based system used in clinical trials is significantly better since the system is designed and built for the purpose of maximizing the advantages of the web and its attributes in the collection of clinical trial data. Examining the two systems shows why.
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