Visual illusions created by survival curves and the need to avoid potential misinterpretation.

Prospective Clinical Trial Registration: A Prerequisite for Publishing Your Results.

Treating the Black Hypertensive in 2010: Achieve Lower Targets While Awaiting More Definitive Evidence

Using GFR, Albuminuria, and Their Changes in Clinical Trials and Clinical Care

Principles of Therapy of HIV Infection and Guidelines for the Use of Antiretroviral Agents in HIV-Infected PersonsJune 15, 1998Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and AdolescentsAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-12_Part_2-199806151-00003 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail AbstractThe availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced extraordinary complexity into the treatment of HIV-infected persons. In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for the clinical management of HIV-infected adults and adolescents.This report recommends that care should be supervised by an expert, and it makes recommendations for laboratory monitoring with particular emphasis on measurement of plasma levels of HIV RNA.It also provides guidelines for antiretroviral therapy, including when to start treatment, what drugs to initiate, when to change therapy, and therapeutic options when changing therapy. Special consideration is given to adolescents and pregnant women. As with decisions about treatment of other chronic conditions, therapeutic decisions about HIV disease require a mutual understanding between the patient and the health care provider regarding the benefits and risks of treatment. Like treatment for most chronic diseases, antiretroviral regimens are complex, have major side effects, pose difficulty with compliance, and carry serious potential consequences with the risk for resistance from nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions is important for all medical conditions but is considered especially critical for HIV infection and its treatment.With regard to specific recommendations, treatment should be offered to all patients with the acute HIV syndrome, those within 6 months of seroconversion, and all patients with symptoms ascribed to HIV infection.Recommendations for offering antiretroviral therapy to asymptomatic patients depend on virologic and immunologic factors. In general, treatment should be offered to individuals with fewer than 500 CD4+ T cells/mm3 or plasma HIV RNA levels exceeding 10 000 copies/mL (branched DNA assay) or 20 000 copies/mL (reverse transcriptase polymerase chain reaction assay). The strength of the recommendation to treat asymptomatic patients should be based on the patient's willingness to accept therapy, the probability of adherence with the prescribed regimen, and the prognosis in terms of time to an AIDS-defining complication as predicted by plasma HIV RNA levels and CD4+ T-cell counts, which independently help predict prognosis. Once the decision has been made to initiate antiretroviral therapy, the goal is maximum viral suppression for as long as possible. Results of clinical trials to date indicate that this may currently be best achieved with a potent protease inhibitor in combination with two nucleoside analogue reverse transcriptase inhibitors (NRTIs). Another option is the combination of saquinavir plus ritonavir combined with one or two NRTIs. Other currently available regimens may be used in selected settings but are considered by many to be less likely to produce maximum viral suppression. Results of therapy are evaluated primarily with plasma HIV RNA levels; these are expected to show a one-log (10-fold) decrease at 8 weeks and no detectable virus (<500 copies/mL) at 4 to 6 months after initiation of treatment. Failure of therapy (i.e., plasma HIV RNA levels >500 copies/mL) at 4 to 6 months may be ascribed to nonadherence, inadequate potency of drugs or suboptimal levels of antiretroviral agents, resistance, and other factors that are poorly understood. Patients whose therapy fails should change to at least two new agents that are not likely to show cross-resistance with drugs given previously; ideally, the regimen should be changed to a completely new regimen that is devoid of anticipated cross-resistance and for which clinical trial data support a high probability of viral response. Rational changes in therapy may be especially difficult to achieve for patients for whom the preferred regimen has failed, because of limitations in the available alternative antiretroviral regimens that have documented efficacy; these decisions are further confounded by problems with adherence, toxicity, and resistance. In some settings, it may be preferable for a patient to participate in a clinical trial with or without access to new drugs or to use a regimen that may not achieve the optimal virologic goal.It is emphasized that concepts relevant to HIV management evolve rapidly.The Panel has a mechanism to update recommendations on a regular basis, and the most recent information is available on the AIDS Treatment Information Service World Wide Web site (http://www.hivatis.org).These Guidelines were developed by the Panel on Clinical Practices for Treatment of HIV Infection convened by the Department of Health and Human Services and the Henry J.Kaiser Family Foundation. Leadership of the Panel consists of Anthony S. Fauci, National Institutes of Health, Bethesda, MD (co-chair); John G. Bartlett, Johns Hopkins University, Baltimore, MD (co-chair); Eric P. Goosby, Department of Health and Human Services (convener); Mark D. Smith, California HealthCare Foundation, San Francisco, CA, formerly of the Henry J. Kaiser Foundation (convener), succeeded by Sophia W. Chang, Henry J. Kaiser Foundation.Members of the Panel who participated in the development of this document included Jean Anderson (Johns Hopkins University, Baltimore, MD), Rodney Armstead (Watts Health Foundation, Inc., Inglewood, CA), A. Cornelius Baker (National Association of People with AIDS, Washington, DC), David Barr (Forum for Collaborative HIV Research, Washington, DC), Samuel Bozzette (San Diego Veterans Affairs Medical Center, San Diego, CA), Spencer Cox (Treatment Action Group, New York, NY), Martin Delaney (Project Inform, San Francisco, CA), Fred Gordin (Veterans Administration Medical Center, Washington, DC), Wayne Greaves (Howard University, Washington, DC), Mark Harrington (Treatment Action Group, New York, NY), John J. Henning (American Medical Association, Chicago, IL), Martin S. Hirsch (Massachusetts General Hospital, Boston, MA), Jeffrey Jacobs (AIDS Action Council), Richard Marlink (Harvard AIDS Institute, Cambridge, MA), Celia Maxwell (AIDS Education and Training Center, Washington, DC), John W. Mellors (University of Pittsburgh, Pittsburgh, PA), David B. Nash (Thomas Jefferson University, Philadelphia, PA), Sallie Perryman (New York State Department of Health, New York, NY), Robert T. Schooley (University of Colorado, Denver, CO), Renslow Sherer (Cook County HIV Primary Care Center, Chicago, IL), Stephen A. Spector (University of California San Diego, La Jolla, CA), Gabriel Torres (St. Vincent's Hospital, New York, NY), Paul Volberding (University of California, San Francisco, CA); participants from the Department of Health and Human Services: Barbara A. Brady (Office of HIV/AIDS Policy), Oren Cohen (National Institutes of Health), Elaine M. Daniels (Office of HIV/AIDS Policy), David Feigal (Food and Drug Administration), Mark Feinberg (National Institutes of Health), Helene D. Gayle (Centers for Disease Control and Prevention), T. Randolph Graydon (Health Care Financing Administration), Jonathan Kaplan (Centers for Disease Control and Prevention), Abe Macher (Health Resources and Services Administration), R. Frank Martin (Indian Health Service), Henry Masur (National Institutes of Health), Lynne Mofenson (National Institutes of Health), Jeffrey Murray (Food and Drug Administration), Joseph O'Neill (Health Resources and Services Administration), Lucille C. Perez (Substance Abuse and Mental Health Services Administration), Richard Riseberg (Office of the Secretary), Samuel Shekar (Health Care Financing Administration), Sharilyn K. Stanley (National Institutes of Health), Jack Whitescarver (Office of AIDS Research). The Panel would like to extend special appreciation to Charles Carpenter (Brown University School of Medicine, Providence, RI) for his advice in the development of this document and Gerry Bally (Health Canada) and Anita Rachlis (Sunnybrook Health Science Centre, University of Toronto, Toronto, Canada) for their participation. The Panel would also like to acknowledge the special contributions of Sharilyn K. Stanley, Barbara A. Brady, and Elaine M. Daniels in the preparation of this document.

Sharing Clinical Trial Data: A Proposal from the International Committee of Medical Journal Editors

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.

Clinical Trial Inclusion of Therapy-Related Myelodysplastic Syndromes (MDS) over the Past 20 Years

In recent years, there has been a growing interest in incorporating patients’ perspectives when measuring and interpreting the clinical benefit of cancer therapies. Patient-reported outcomes (PROs) are used in a variety of cancer clinical trials. These studies range from using PROs to better understand the burden of cancer and the adverse effects of cancer therapy (such as pain), to studies that use PROs as the primary end point of the clinical trial, such as reducing symptoms like nausea or fatigue that can be caused by certain cancer therapies. The evolution of PROs in cancer trials has been recently documented by the National Cancer Institute (NCI)–supported Cancer Outcomes Measurement Working Group and by the US Food and Drug Administration’s recent guidance for the use of PROs in product labeling. PRO research also has been recognized as an important element in the NCI strategic planning process. A major NCI goal is to support research that enhances our understanding of the burden of disease among patients with cancer and cancer survivors, and reduces the sequellae of cancer throughout the continuum of care. NCI has taken an important role in developing new ways to measure patient-reported symptoms such as pain and fatigue, and aspects of health-related quality of life across a wide range of cancers and other diseases, through the Patient Reported Outcomes Measurement Information System (PROMIS). As a National Institutes of Health Roadmap initiative, PROMIS will provide clinical research communities with a reliable, valid, and standardized approach to capture these clinically relevant, but subjective and difficult-to-measure outcomes in clinical trials. Standardization of these data will provide additional benefits to the cancer clinical trial enterprise because it will eventually facilitate their incorporation into the cancer bioinformatics grid (ca-BIG), thereby making PROs available to all researchers who participate in and use the grid to support correlative research studies in connection with clinical trials. Through the NCI Clinical Trials Working Group (CTWG), NCI also has undertaken a major reassessment of the design, review, funding, and implementation of cancer clinical treatment trials and symptom management trials. Among the many recommendations contained in the CTWG report are ones to establish a new funding mechanism and prioritization process for supporting correlative science and quality-of-life studies using PROs, that can be initiated in association with clinical trials. As part of the CTWG process, NCI recently created a Symptom Management and Health-Related Quality of Life (SxQOL) Steering Committee to prioritize and review studies that include PROs as primary end points in symptom management clinical trials, and PROs as secondary end points in phase III Cooperative Group cancer treatment trials sponsored by the NCI. In addition, the SxQOL committee will provide guidance on how to improve the utility of PROs in cancer treatment trials and in symptom management trials. Although PRO data have potential utility for a variety of analyses in cancer clinical trials, the issues surrounding their appropriate and effective application are complex. In September 2006, the NCI convened a 2-day conference entitled “PatientReported Outcomes Assessment in Cancer Trials (PROACT): Evaluating and Enhancing the Payoff to Decision-Making.” This conference was cosponsored by the American Cancer Society and represented a collaborative effort among the leadership from all major NCI extramural divisions involved with clinical trials—the Division of Cancer Treatment and Diagnosis, the Division of Cancer Prevention, and the Division of Cancer Control and Population Sciences. The goal of the PROACT conference was to bring together scientists working in this area to inform NCI and the broader cancer research and policy community on how the NCI clinical trial infrastructure is currently organized to support PRO research in clinical trials, and to identify the issues and lessons learned from the experiences of NCI-sponsored cooperative groups and Community Cancer Oncology Programs; other national and international researchers; and US pharmaceutical industry experts in using PROs in phase II and III cancer treatment trials, as well as in symptom management trials. Before the conference, NCI charged a multidisciplinary Scientific Program Committee of internationally recognized experts to identify key determinants of the successful application of PROs in JOURNAL OF CLINICAL ONCOLOGY O V E R V I E W VOLUME 25 NUMBER 32 NOVEMBER 1

Discovering and developing new drugs/ medicines is very crucial for the pharmaceutical industry. The increasing number of drugs approved in recent years demonstrates the impact of modern drug discovery approaches, digital technologies, and automated drug development methodologies. Drug development is a systematic and methodological process of developing a new pharmaceutical drug once the process of Drug discovery has identified the prime pharmacological component. The structured sequence of steps followed for drug development aims to ensure the safety and efficacy of the drug being developed. It includes pre-clinical research on microorganisms and animals, preparation of detailed data with respect to pharmacology, pharmacokinetics and toxicology details, application and approval by regulatory authorities and conduction of clinical trials. The conduction of clinical trials is an expensive affair as it needs a collaborative effort by multiple stakeholders along with a high level of monitoring and regulation. The data generated during the lifecycle of clinical trials is very critical for pharmacological scientific publications, regulatory approval for the target drug and post-marketing surveillance that ultimately leads to the development of better decision support systems for drug development. Hence, the data integrity of such data is of prime importance. Several Clinical data management (CDM) systems have been developed to ensure seamless collection and management of clinical trial data. These CDM systems enable useful analysis and decisions supported by authentic data. However, such systems face several security challenges with respect to privacy, integrity and authenticity of the clinical data. Another major challenge in conducting the clinical trials is finding the appropriate willing candidate who is physically and clinically suitable for the study. In view of the above, it is highly desirable to have a technology component that can address the above-mentioned issues. In this chapter, the technologies like blockchain and cloud computing have been introduced to address the challenges posed by clinical trial data management. The paper also proposes a blockchain based secure clinical data management system. The proposed system intends to help the data security issues like data integrity, privacy, ease and quick access to immutable clinical trial data with thorough access control enabling greater transparency and accountability.

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

Background and rationale for mechanism of action, efficacy, and safety of fingolimod (Gilenya), the first oral therapy for remitting-relapsing multiple sclerosis

The value proposition of investigator-initiated clinical trials conducted by networks.

The COVID-19 pandemic has far-reaching ramifications for patients undergoing cancer treatment. Oncologists and institutions have adjusted treatment practices and, in many cases, significantly curtailed clinical trial conduct. Whether these adjustments mitigate the risk of COVID-19 complications without jeopardizing treatment of the cancer is unknown. Given the expected duration of the pandemic, it is imperative that treatment of the patient's cancer remain the priority and that advances in drug development continue through appropriately designed clinical trials.

AGA Clinical Practice Update on Management of Inflammatory Bowel Disease in Elderly Patients: Expert Review

Are adaptive randomised trials or non-randomised studies the best way to address the Ebola outbreak in west Africa?