Source: Ending medical reversal
From the book review
Guest post by Vinayak K. Prasad, MD, MPH, and Adam S. Cifu, MD
For doctors, it is common to have some doubt about a new medical test, procedure or drug—even one which is widely hailed as remarkable or a game changer. It is not cynicism but a healthy skepticism towards marketing over substance. Doctors want to see the evidence that a drug actually works rather than just a good story about why it should work.
Often, however, this skepticism does not last. After a few months, still without any evidence, the doctor finds herself buying in, just a little, to the hype. OK, let me just see what everyone is talking about, she thinks. She begins recommending the drug herself. She still thinks of herself as cautious and conservative—while her colleagues use the treatment widely, she thinks it has a more narrow and defined role. Probably the pill does not work for everyone, but in a select group of people.
A few more years go by, and she gets comfortable with the once-hyped treatment. She now knows how to manage its complications; she thinks she has a good sense of who it benefits; and she considers it a part of her practice.
Then, one day, she opens one of the nation’s top medical journals and discovers that the treatment she was once skeptical of, but slowly grew to accept, simply does not work. A well-done clinical trial, probably the one which should have been done before the treatment even came to market, compared the treatment to the prior therapy, and found no benefit.”
A new study by investigators from the University of North Carolina at Chapel Hill School of Medicine has confirmed the existence of a “trial effect” in clinical trials for treatment ofHIV.
Trial effect is an umbrella term for the benefit experienced by study participants simply by virtue of their participating in the trial. It includes the benefit of newer and more effective treatments, the way those treatments are delivered, increased care and follow-up, and the patient’s own behavior change as a result of being under observation. …
Adding research-centred approaches into the day-to-day life of the doctor’s clinic strengthens clinical decisions, according to a new report by the European Medical Research Councils. The “Implementation of Medical Research in Clinical Practice” report launched at the European School of Management and Technology in Berlin, Germany.
The report examines the quality of clinical research, and how using research in clinical practice can improve treatment. An important theme is tightening the relationship between doctors, patients and researchers, such as involving GPs in clinical trials to get a better idea of how treatments work in a wider range of patients, beyond the controlled environment of a hospital.
“Medical care has improved greatly in the last 50 years, underpinned by progress in clinical research,” said Professor Liselotte Højgaard, chair of the European Medical Research Councils, part of the European Science Foundation (ESF). “But we cannot be complacent. We want new findings to be introduced into clinical practice as speedily and efficiently as possible, so that evidence-based medicine is used in each and every patient treatment.”…
Greater international collaboration between countries could help with systematically reviewing treatments, through shared databases on protocols, data, and health technology assessments. The report recommends actively using evidence-based clinical practice guidelines, as well as promoting rigorous reporting for clinical studies. Health technology assessment reports and clinical guidelines are strongly advised for hospitals and primary care facilities, as well as for administrative processes including financing of treatment and technologies. ….
- Do Doctors Resist Reform? The Case of Evidence-Based Medical Practice (larrycuban.wordpress.com)
- IOM recommends standards to achieve reliable clinical practice guidelines (eurekalert.org)
ScienceDaily (May 10, 2011) — Medicines regulators are protecting drug company profits rather than the lives and welfare of patients by withholding unpublished trial data, argue researchers on the British Medical Journal website.
They call for full access to full trial reports (published and unpublished) to allow the true benefits and harms of treatments to be independently assessed by the scientific community.
Despite the existence of hundreds of thousands of clinical trials, doctors are unable to choose the best treatments for their patients because research results are being reported selectively, write Professor Peter Gøtzsche and Dr Anders Jørgensen from the Nordic Cochrane Centre in Denmark.
Selective reporting can have disastrous consequences. For example, Rofecoxib (Vioxx) has probably caused about 100,000 unnecessary heart attacks in the USA alone, while anti-arrhythmic drugs have probably caused the premature death of about 50,000 Americans each year in the 1980s…..
P. C. Gotzsche, A. W. Jorgensen. Opening up data at the European Medicines Agency. BMJ, 2011; 342 (may10 1): d2686 DOI: 10.1136/bmj.d2686 [Links to the free full text of the article]
- Are overseas trials generating suspect data on new drugs? (fiercebiotech.com)
Experts today challenge the view that popular drugs to prevent disease – like statins and antihypertensives to prevent heart disease andstroke, or bisphosphonates to prevent fractures – represent value for money.
In a paper published on bmj.com[full text] today, Teppo Järvinen and colleagues argue that the benefits seen when these drugs are tested in clinical trials may not apply in the real world.
They argue that value for money in real life clinical practice is likely to be much lower than in a clinical trial, where patients are carefully selected and receive special attention from dedicated staff. “This gap between the ideal and clinical circumstances raises the question of how well our most widely used preventive drugs work in real life,” they write. ….
…although there are claims that important preventive drugs such as statins, antihypertensives, and bisphosphonates are cost effective, there are no valid data on the effectiveness, and particularly the cost effectiveness, in usual clinical care,” they say.
Despite this dearth of data, they point out that the majority of clinical guidelines and recommendations for preventive drug therapy rest on these claims.
The authors argue that before claims on cost effectiveness can be used to guide treatment policies and practices, it should be adequately proven by testing in a real-world setting. …
- Clinical Trials: Crafting the Label (biostrategics.wordpress.com)
- Prescriptions – Good or Bad? (georgevanantwerp.com)
- Regulatory requirements: differences or similarities between FDA and EMA? (sopwriting.wordpress.com)
- Generics Dominate Scripts in 2010
In 2010, generics captured 78% of the total market share for prescriptions, up from 63% in 2006
- Dietary Calcium And Supplements Recommended Instead Of Bone-Building Meds (Medical News Today, May 3, 2011)
- Statins and bone drugs ‘not cost effective’ (telegraph.co.uk)
From an April 8 2011 Science Daily report
ScienceDaily (Apr. 8, 2011) — Doctors at the Veterans Affairs Boston Healthcare System are testing a new kind of clinical trial that’s not only less costly but guides doctors to switch to the best treatment even before the trial is completed. The new approach — called a point-of-care clinical trial — was developed by Stanford University biostatistician Philip Lavori, PhD, and a Boston-based team as an alternative to expensive, lengthy, double-blind, placebo-controlled clinical trials to compare drugs and procedures that are already in regular use.
“The goal of point-of-care clinical trials is to deliver the best care to patients while learning from each experience and redefining that care,” said Lavori, a professor of health research and policy at Stanford’s School of Medicine and the senior author of an article on the method to be published online April 4 in Clinical Trials. “This ‘learning and improving’ loop will enable health-care institutions to more rapidly fold improvements into their medical practices,” he said….
…”The idea of embedding research into clinical care has been around for quite awhile but to my knowledge this is the first time that a randomized trial has been fully integrated into a hospital’s informatics system,” said Fiore. “It demonstrates an effective way to use electronic medical records to improve health care at a local level.”…
- R. A. Rosenheck, J. H. Krystal, R. Lew, P. G. Barnett, S. S. Thwin, L. Fiore, D. Valley, G. D. Huang, C. Neal, J. E. Vertrees, M. H. Liang. Challenges in the design and conduct of controlled clinical effectiveness trials in schizophrenia. Clinical Trials, 2011; DOI:10.1177/1740774510392931
ScienceDaily (Mar. 8, 2011) — It’s all too familiar: researchers announce the discovery of a new drug that eradicates disease in animals. Then, a few years later, the drug bombs in human trials. In the latest issue of the journal PLoS Medicine, ethics experts Jonathan Kimmelman, associate professor at McGill’s Biomedical Ethics Unit and Department of Social Studies of Medicine, and Alex John London, associate professor of philosophy at Carnegie Mellon University, argue that this pattern of boom and bust may be related to the way researchers predict outcomes of their work in early stages of drug development.
The study suggests researchers focus too narrowly on pre-clinical data, which leads to overoptimistic predictions. It is also possible that drug bias is not as rigorous in animal testing than in human testing.
DALLAS – Feb. 3, 2011 – UT Southwestern Medical Center psychiatry researchers(Division of Addictions)are leading the Texas arm of a national network that conducts clinical trials aimed at finding effective treatments for drug addiction.
More than 100 community treatment providers and academic medical centers throughout the country are funded in part through the National Institute on Drug Abuse’s Clinical Trials Network (CTN). The Texas component includes partnerships between academic and community treatment providers in Dallas, El Paso, Austin and Houston. It is led by Dr. Madhukar Trivedi, professor of psychiatry at UT Southwestern.
“The effects of drugs on the brain are very clear, but we still need long-term answers that cure people who abuse drugs and prevent them from relapse,” Dr. Trivedi said. “I applaud NIDA for funding the infrastructure at academic institutions to research therapies in real-world treatment centers that will lead to ready-to-launch cures. Drug abuse affects not just the person, but families and society as a whole.”
Each CTN study is conducted in multiple community treatment provider sites across the country, led by a CTN substance abuse researcher and supported by the researchers in the CTN academic institutions affiliated with each participating site.
“It is critical to find new treatments in the substance abuse field where current treatments result in only modest improvements. Finding effective interventions really requires larger, multicenter treatment trials like those occurring in the CTN,” Dr. Trivedi said.
One such national study within the CTN is the Stimulant Reduction Intervention Using Dose Exercise (STRIDE)**, led by Dr. Trivedi. It is a groundbreaking study that tests the short and longer term effectiveness of adding either exercise or health education to treatment as usual in adults who abuse stimulants such as cocaine or methamphetamine. Sites participating in this study in Texas include Nexus Recovery Center and Memorial Hermann Prevention and Recovery Center as well as multiple other sites across the country.
Other studies being conducted in the CTN in Texas include a trial that tests whether an interactive web-based therapy added to usual treatment improves abstinence from drug use, and a trial that examines whether medication, counseling, and incentives to quit smoking added to usual treatment improve abstinence from drug use.
Dr. Trivedi recently received a renewal of the National Institute on Drug Abuse‘s grant to continue contributions to improve the treatment of addiction for several additional years and said he expects to receive nearly $4 million over the next year.
A national CTN goal for the next few years is to engage other types of medical doctors and treatment settings who treat people addicted to drugs, in research, including primary care, internal medicine and emergency-room physicians. “We will be expanding our reach,” Dr. Trivedi said.
Call for clinical trial raw data to be freely available to all (& a related call from the scientific community)
A recent BMJ editorial (Goodbye PubMed, hello raw data) ****calls for clinical raw data to be freely available to everyone.
The author cites the example of the influenza drug oseltamivir manufactured by Roche.
Reviewers for Cochrane Reviews asked Roche to release clinical trial data so they could systematically and comprehensively review antivirals as flu treatments. Roche refused, leaving the reviewers with inadequate incomplete information to complete their analysis.
The editor ends his article with these paragraphs…
From now on, they say, reviewers must have access to all unpublished data, not only from unpublished trials—the usual focus of concern about publication bias—but also from those that have been published in peer reviewed journals. Reviewers must assess entire trial programmes, and so new tools and methods are needed. If the trial reports are incomplete, reviewers should turn to reports from the drug regulators. As Tom Jefferson, the lead author for the Cochrane review, told me, “it’s goodbye PubMed, goodbye Embase.”
The reviewers have posted their new style protocol for this review on the Cochrane site and, recognising the enormity of the task, they are recording how much work is involved. But it must be clear to everyone that such a heroic approach is unsustainable across the whole of healthcare, given the resource constraints on academics and regulators. Which brings us back to what seems to be the only real solution—that the raw data from trials must be made freely available. Journals clearly have a role to play in making this happen, as An-Wen Chan agrees in his editorial (doi:10.1136/bmj.d80). The International Committee of Medical Journal Editors meets in a few months’ time. This will be on the agenda.
Scientists also see the need for access to research data.
The entire 2011 January/February issue of D-Lib Magazine is devoted to this topic.
**Cochrane Reviews are part of the Cochrane Collaboration, which
strives to provide the best evidence for health care. Cochrane reviews involve specific interventions in a specific clinical context, as antivirals for flu prevention in healthy adults. Individual reviews involve extensive literature research performed by independent teams of professionals.
Most reviews are only available through a paid subscription to the Cochrane Collaboration. However, many medical and academic libraries subscribe to the Cochrane Collaboration. Contact an academic reference librarian to see if they subscribe and if they provide access to the public.
****Via a MedLib posting by medical librarian Susan Fowler
How do data exclusivity periods affect pharmaceutical innovation?
Study is first to estimate financial and social impact of extending exclusive access to clinical trial data for conventional drugs
LOS ANGELES, Calif. — January 6, 2011 — Pharmaceutical companies and generic drug manufacturers have long been at odds over regulations about “data exclusivity,” the period of time before generic manufacturers can make use of valuable clinical trial data.
A new study in the January 2011 issue of Health Affairs *** is the first to calculate the financial and social costs of limiting access to trial data — and finds that extending the term of exclusive access will lead to higher drug costs in the short term but also to more than 200 extra drug approvals and to greater life expectancy in the next several decades.
“Elected officials are unlikely to embrace legislation that would result in higher drug prices, but our research suggests that legislation to extend data exclusivity would spur innovation that would benefit future generations,” explained Dana Goldman, lead author, director of the Schaeffer Center for Health Policy and Economics at USC and Norman Topping Chair in Medicine and Public Policy at USC.
The pharmaceutical companies that introduce new drugs are currently granted five years of exclusive access to the clinical trial data they submit during the approval process. An extension of three years is available if new applications arise and a six month extension is granted if the drug is approved for use in pediatric populations.
In 2007, the National Academies Committee on Science, Engineering and Public Policy called for extending this “data exclusivity” term to the longer period used in Europe, ten to 11 years. But generic manufacturers have argued for shorter limits so that they can bring less expensive versions of drugs to patients sooner.
“Unfortunately, the health policy literature contains no information about the effects such a policy would have on innovation, population longevity and social welfare,” said Darius Lakdawalla, research director at the Schaeffer Center at USC and associate professor in the USC School of Policy, Planning and Development.
In the first study to directly address these issues, the researchers estimate that extending the term of data exclusivity to 12 years would increase the lifetime revenue of a drug by 5 percent, on average.
With empirical evidence that profits drive drug innovation, this longer term would lead to an additional 228 drug approvals over the next fifty years and an increase of 1.7 months in average life expectancy, according to the study.
John Romley, an economist with the Schaeffer Center at USC and research assistant professor at the USC School of Policy, Planning and Development, acknowledged the trade-off between current and future generations: “Americans in the early 2020’s would bear the cost of increasing drug spending. However, people turning 55 in 2060 could expect increased life expectancy as a result of innovation in the interceding years — that is, new drugs brought to market because of lengthier data exclusivity.”
Communication in Cancer Care is a PDQ (Physician Data Query) summary** which outlines good communication skills among patients, family members, and health care providers. Good communication in all phases of cancer care contributes to the well being of the patient and improves quality of life.
The patient version addresses issues as the roles of family givers and parents, how to talk with the health care team (including the importance of checklists and record keeping)
and where to find more information on communicating effectively in cancer care settings.
The health professional version outlines factors and outcomes related to communicating effectively, how to communicate effectively in cancer care settings, and information on training programs and clinical trials.
On a related note, this is an example of why good communication is important in cancer care…
The Perils of Taking Experimental Cancer Drugs [Reuters Health, Oct 26,2010, by Frederik Joelving]
NEW YORK (Reuters Health) – Trying a new, experimental cancer drug may offer a glimpse of hope for very sick patients, but often does more harm than good, a new study shows.
Researchers said cancer doctors regularly resort to drugs still undergoing testing, as long as they have been approved for other diseases or in different combinations or doses.
But because the science is still up in the air, nobody really knows what the consequences of taking such drugs are.
“Many of these drugs end up not being the tremendous improvement that we hoped they would be,” said Dr. Otis Brawley, chief medical officer of the American Cancer Society, who was not involved in the new study.
“People need to realize that because the trials have not been completed there is a great deal that is not known about the treatments,” he told Reuters Health. “There are people who get these treatments and get hurt.”
The new study, published in the Journal of Clinical Oncology, looked at 172 clinical trials published over two years. [Editor Flahiff’s note : Ask a reference librarian at a local public, academic, or medical library for availability and if any fee is involved]
Less than a third of the clinical trials showed the experimental drugs improved patient survival, and less than half found the drugs helped other clinical outcomes…..
Sometimes, of course, new drugs do work, and no one argues that doctors shouldn’t be allowed to prescribe medications they think will help patients.
But doctors should be very clear about the high risks involved. One way to do that, said Peppercorn, would be to require that cancer doctors get informed consent from patients before they start them on experimental drugs.
In the end, Brawley said, the decision to use such treatment should be left to the patient and his or her doctor.
“There are times when it can be justified,” he noted, “but it is done far more often than it should be.”
**PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, complementary and alternative medicine, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information, and more specific information about PDQ, can be found on the NCI’s Web site athttp://www.cancer.gov/cancertopics/pdq. Also called Physician Data Query.
From the blog Open Medicine dated October 4th, 2010
Bastian H, Glasziou P, Chalmers I (2010) Seventy-Five Trials and Eleven Systematic Reviews a Day: How Will We Ever Keep Up? PLoS Med 7(9): e1000326. doi:10.1371/journal.pmed.1000326
Published: September 21, 2010
- When Archie Cochrane reproached the medical profession for not having critical summaries of all randomised controlled trials, about 14 reports of trials were being published per day. There are now 75 trials, and 11 systematic reviews of trials, per day and a plateau in growth has not yet been reached.
- Although trials, reviews, and health technology assessments have undoubtedly had major impacts, the staple of medical literature synthesis remains the non-systematic narrative review. Only a small minority of trial reports are being analysed in up-to-date systematic reviews. Given the constraints, Archie Cochrane’s vision will not be achieved without some serious changes in course.
- To meet the needs of patients, clinicians, and policymakers, unnecessary trials need to be reduced, and systematic reviews need to be prioritised. Streamlining and innovation in methods of systematic reviewing are necessary to enable valid answers to be found for most patient questions. Finally, clinicians and patients require open access to these important resources. [editor Flahiff’s emphasis]
If the results of a clinical study are published in a scientific journal, PubMed is the best way to search for information about the article. If you are having challenges searching PubMed, consider the tutorial at the home page of PubMed. You may also ask a reference librarian at a local public, academic, or medical library. Call ahead to see what level of assistance they offer.
Clinicaltrials.gov has the voluntary summaries of some clinical trials. Advanced search has the option Study results (select Studies With Results). Some results may be labelled “proprietary” (information not released to the public, sometimes called “industry secrets” ).
Tropical diseases affect millions of people with effects ranging from extreme pain to permanent disability to death.
Currently the National Institute of Allergy and Infectious Diseases (NIAID) conducts research and clinical studies for many of these diseases (examples of tropical diseases may be found here).
If you would like to volunteer for clinical trials on tropical diseases, go here for further information.
Biomedical research results are increasingly available to the public. However, caution is urged in interpreting results. For example, be very careful to not confuse causation with association.
(A recent news item about insulin use and cancer is very controversial. Some say insulin use can cause cancer, while others insist insulin users are predisposed to cancers.)
The MedlinePlus Topic Page Understanding Medical Research has links to tutorials, overviews, and more
A sampling of links
**Increasing Knowledge — How to Read a Research Paper(Lewy Body Dementia Association)
** Clinical Research & Clinical Trials(National Institute of Child Health and Human Development)
**Making Sense of Medical News (Nemours Foundation)
Related Blog Items
- NLM released several exciting enhancements that improve users’ ability to share and consume MedlinePlus content: (jflahiff.wordpress.com)
- Improving Health Care Decisions By Putting Research Into Practice (jflahiff.wordpress.com)
Excerpts from the news article:
Medical journals should include more clinical details in cancer research studies to help doctors better understand and utilize results, according to U.S. researchers.
[The researchers] analyzed 262 articles published from 2005 to 2008 in the Journal of Clinical Oncology, The New England Journal of Medicine, the Journal of the National Cancer Institute, and the journals Cancer and Blood.
Only 11 percent of the articles offered all the information required by doctors in order to prescribe and monitor new cancer therapies, said the researchers at the University of Florida in Gainesville.
The dose of the drug was almost always reported in the articles, but only 43 percent reported what premedication was necessary, and only 42 percent provided details about adjusting dosages if the therapy proved toxic to patients.
In fiscal year 2008, 80 percent of approved marketing applications for drugs and biologics contained data from foreign clinical trials. Over half of clinical trial subjects and sites were located outside the United States.
This poses major challenges to the US Food and Drug Administration (FDA) in monitoring and inspecting clinical trials worldwide.
Report’s findings include the following:
- FDA should require standardized electronic clinical trial data and create an internal database
- FDA should monitor trends in foreign clinical trials not conducted under INDs.
- FDA should continue to explore ways to expand its oversight of clinical foreign trials.
A related news item may be found here.
The complete report may be found here.