Drugs Receiving Accelerated FDA Approval Often Have Flaws In Their Evidence Base

MedicalResearch.com Interview with:

Huseyin Naci, PhD Assistant Professor of Health Policy LSE Health Department of Social Policy London School of Economics and Political Science London, United Kingdom

Dr. Naci

Huseyin Naci, PhD
Assistant Professor of Health Policy
LSE Health
Department of Social Policy
London School of Economics and Political Science
London, United Kingdom 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: An increasing proportion of novel therapeutic agents are entering the market on the basis of expedited development and approval programs. The Food and Drug Administration’s (FDA) Accelerated Approval pathway is one such expedited approval program. In our study, we examined the dynamics of research on drugs receiving accelerated approvals. We were particularly interested in the timing and characteristics of research studies including drugs with accelerated approvals.

Our primary findings are the following:

  • First, there is an abundance of research on drugs receiving accelerated approvals. Yet, the majority of this research (about 70%) is of poor quality. Ideally, these drugs are evaluated in so-called randomised controlled trials to establish their efficacy and safety. However, only about a third of all existing studies are randomised controlled trials.
  • Second, a substantial share (about 30%) of the existing research on these drugs is in areas not approved by the FDA. This may be indicative of industry research practices in trying to prioritise identification of new uses for drugs receiving accelerated approvals instead of strengthening their evidence base.
  • Third, when focusing on well-designed studies, only about a half actually evaluate the effectiveness of the accelerated approval drugs. The rest appears to use the accelerated approval drug as background therapy. Interestingly, these two types of studies are conducted concurrently. In other words, while one research group is trying to find out if an accelerated approval drug is effective, other research groups are already using it as part of a background regimen when testing the effectiveness of another, potentially newer drug

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Research Oriented Hospitals Found To Be More Efficient

MedicalResearch.com Interview with:
Antonio García-Romero IE University – IE Business School Madrid, SpainAntonio García-Romero
IE University – IE Business School
Madrid, Spain

MedicalResearch.com: What is the background for this study?

Response: There is an increasing need for new approaches capable of measuring the “real” effects of research on society. People are interested in knowing what benefits are obtained from scientific research. Our aim in this project was to develop a valid methodology capable of measuring the effects from scientific research on some healthcare outcomes such as the average length of stay in a hospital. Our central hypothesis is that the more research is carried out in hospitals, the more efficient the hospitals are regarding the length of stay (LOS).

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Submission and Publication Bias Against Studies With Negative Results Declining

MedicalResearch.com Interview with:
Gary Evoniuk, PhD

Director of Publication Practices, Medical Communications Quality & Practices
GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709

MedicalResearch.com: What is the background for this study?

Response: In recent years, industry, and to a lesser extent academia, have been criticised for failing to submit clinical trial data for publication, especially when the data are perceived to be “negative”, (i.e. unfavourable to the drug under study) leading to publication bias. We felt it was important to determine whether this criticism is based on perception or reality and so we conducted what is, to our knowledge the only study to systematically address the issue of submission and publication bias based on study outcome.

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Financial Ties of Principal Investigators Associated With Positive Outcomes

MedicalResearch.com Interview with:
Salomeh Keyhani MD
Associate professor of general internal medicine
San Francisco VA Medical Center and University of California
San Francisco, CA 94121, USA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Randomized controlled trials are the foundation of the evidence base. We examined the prevalence of financial ties in randomized controlled trials and also examined the relationship of financial ties of principal investigators (PI) with trial outcome. We defined a financial tie as the direct compensation (e.g., consulting fees) of a PI by the drug manufacturer of interest. Although there have been past studies that have examined this relationship, many did not separate financial ties from funding source for the trial and many were focused on one specialty, journal, or type of drug.

This study identified a random sample of RCTs published in 2013 that were focused on assessing drug efficacy. Both the disclosure section of the paper and several online databases (Medline, Google, Propublica’s Dollars for Doctors, and the US Patent Office) were searched for evidence of financial ties. Principal investigators financial ties with industry were independently associated with positive study outcomes.

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Teashirt Gene Links Kidney Disease and Autism Spectrum Disorders

MedicalResearch.com Interview with:

Prof Adrian S. Woolf Chair, Professor of Paediatric Science  University of Manchester, UK

Prof. Adrian Woolf

Prof Adrian S. Woolf
Chair, Professor of Paediatric Science
University of Manchester, UK

MedicalResearch.com: What is the background for this study?

Response: Several years ago, Laurent Fasano discovered that the Drosophila teashirt gene was needed to pattern the body of embryonic flies.

He then found that this transcription factor had three similar genes in mammals.

Working with Adrian Woolf in the UK, they found that Teashirt-3 (Tshz3) was needed in mice to make muscle form in the ureter When the gene was mutated, mice were born with ureters that were ‘blown-up’ and they failed to milk urine from the kidney with the bladder.

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Authors’ Prestige May Influence Some Medical Research Reviewers

MedicalResearch.com Interview with:

Kanu Okike MD MPH Department of Orthopaedic Surgery, Kaiser Moanalua Medical Center Honolulu, Hawaii

Dr. Kanu Okike

Kanu Okike MD MPH
Department of Orthopaedic Surgery, Kaiser Moanalua Medical Center
Honolulu, Hawaii

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Many journals in the social sciences practice double-blind review, in which reviewers and authors are both blinded to each others’ identities. In medicine, on the other hand, most journals practice single-blind review, in which authors’ identities are known to reviewers. Concerns have been raised that this could lead to biased reviews, however, especially in the case of well-known authors.

In our study, we composed a fabricated test manuscript and randomized reviewers for an orthopaedic journal to receive single-blind (prestigious authors listed) or double-blind (no authors listed) versions. In our study, the reviewers who were under the impression that the manuscript was written by prestigious authors (single-blind review) awarded higher marks and also recommended acceptance more often, in spite of the fact that the manuscripts were otherwise identical.

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Reporting of Adverse Events in Published and Unpublished Studies of Health Care Interventions May Differ

MedicalResearch.com Interview with:

Dr Su Golder PhD Research Fellow Department of Health Sciences University of York

Dr. Su Golder

Dr Su Golder PhD
Research Fellow
Department of Health Sciences
University of York

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Serious concerns have emerged regarding publication bias or selective omission of outcomes data, whereby negative results are less likely to be published than positive results. There remains considerable uncertainty about the extent of unpublished data on adverse events beyond that reported in the published literature. We aimed to estimate the potential impact of additional data sources and the extent of unpublished information when conducting syntheses of adverse events.

We found that less published papers contain adverse events information. The median percentage of published documents with adverse events information was 46% compared to 95% in the corresponding unpublished documents. There was a similar pattern with unmatched studies, for which 43% of published studies contained adverse events information compared to 83% of unpublished studies.

We also found even when adverse events are reported in the published and unpublished versions of the same study that the numbers of adverse events do not always match The percentage of adverse events that would have been missed had each analysis relied only on the published versions varied between 43% and 100%, with a median of 64%.
Lastly we found that inclusion of unpublished data increased the precision of the pooled estimates (narrower 95% confidence intervals) in three-quarters of pooled analyses, but did not markedly change the direction or statistical significance of the risk in most cases.

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Early Menopause Linked To Increased Risk of Heart Disease and Carotid Atherosclerosis

MedicalResearch.com Interview with:
Taulant Muka, MD, MPH, PhD
Postdoctoral Researcher
Erasmus University, Rotterdam

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Menopause marks a major life transition for women, resulting in the loss of ovarian follicle development. Although menopause is a universal phenomenon among women, the timing of the final menstrual period differ greatly between women, and is considered a marker of aging. By quantifying data of nearly 310,329 non-overlapping women, we found that women who experienced an early menopause (i.e. younger than 45 years) have an excess risk of CHD, CVD-mortality and all-cause mortality. Furthermore, being 45-49 years at menopause compared to ≥50 years was associated with increased risk of carotid atherosclerosis.

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Risk of breast cancer associated with a diagnosis of atypical ductal hyperplasia may be lower than previously reported

MedicalResearch.com Interview with:
Tehillah S. Menes, MD

Department of Surgery
Tel Aviv-Sourasky Medical Center
Tel Aviv, Israel

MedicalResearch.com: What is the background for this study?

Response: Atypical ductal hyperplasia (ADH) is a known risk factor for breast cancer. The diagnosis is made by a biopsy showing a uniform proliferation of cells lining the ducts of the breast. These cells have monomorphic round nuclei and characteristically fill only part of the involved duct. Women diagnosed with ADH are recommended to undergo increased surveillance and offered chemoprevention (i.e. Tamoxifen) for risk reduction.
Most studies reporting on the risk of subsequent breast cancer in women with ADH were done prior to the wide use of screening mammography and percutaneous needle biopsy. Our study examined 10-year risk of invasive breast cancer in women diagnosed with ADH (by needle biopsy or excisional biopsy), using data collected by the Breast Cancer Surveillance Consortium (BCSC).

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Localized Prostate Cancer: Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy

MedicalResearch.com Interview with:

Professor Jenny Donovan  PhD   OBE FMedSci NIHR-SI AcSS FFPHM Director, NIHR CLAHRC West (National Institute for Health Research Collaboration for  Leadership in Applied Health Research and Care West) at University Hospitals Bristol NHS Trust Bristol, UK

Prof. Jenny Donovan

Professor Jenny Donovan  PhD
OBE FMedSci NIHR-SI AcSS FFPHM
Director, NIHR CLAHRC West
(National Institute for Health Research Collaboration for
Leadership in Applied Health Research and Care West)
at University Hospitals Bristol NHS Trust
Bristol, UK

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: PSA testing identifies many men with prostate cancer, but they do not all benefit from treatment. Surgery, radiation therapy and various programs of active monitoring/surveillance can be given as treatments for fit men with clinically localized prostate cancer. Previous studies have not compared the most commonly used treatments in terms of mortality, disease progression and patient-reported outcomes. In the ProtecT study, we used a comprehensive set of validated measures, completed by the men at baseline (before diagnosis), at six and 12 months and then annually for six years.

The main finding is that each treatment has a particular pattern of side-effects and recovery which needs to be balanced against the findings from the paper reporting the clinical outcomes (Hamdy et al).

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