Tag: Clinical Trials

When Is Closing an Ongoing Clinical Trial a Betrayal of Participants?

Nov 11, 2013• 1

By Cynthia Chauhan & Mary Lou Smith

We have become aware of several instances of precipitous and, in our view, egregious and unjustified closures of on-going clinical trials in which a substantial number of patients were already participating in investigational efforts, some involving biopsies for research purposes.

These closures raise serious ethical issues for the research community. We will discuss those issues and some possible changes in how trials are conducted to address the problem. It is our premise that closing on-going clinical trials without scientific, efficacy, or safety justification is an abhorrent affront to all participants in clinical research as well as a fundamental betrayal of the trust that motivates patient participants to enroll in clinical trials.

Cancer patients who accept the risk of an investigational drug are true partners in bringing new agents to market. They hope they will benefit but, regardless of personal benefit/response, they hope the researchers will learn something to help other patients. Patients participate in clinical research for multiple reasons but, particularly in the case of agreeing to undergo mandatory research biopsies, do so because the research has the potential to improve the care, treatment approach, and standards for cancer patients.

They engage in a relationship with researchers based on their trust in the integrity of the researchers and the system within which the researchers work. Any cavalier approach to the commitment patients make to research is indefensible and particularly reprehensible when participants undergo internal organ biopsies.

Violating the trust of these patients also violates the trust the patients place in the investigators, undermining patient confidence in and availability for research. That trust and any violation of it are deepened when the researcher is also a given patient’s treating oncologist.

It is with good reason that human beings who enroll in clinical trials are called participants, not subjects. A participant is one who takes part in something—an active, volitional partner or colleague. A subject is one, mouse or human, who is under the power or authority and at the incontestable will of another or others. That difference between a participant and a subject is significant and germane to this discussion of when and why it is or is not appropriate to close a clinical trial.

The Government Shutdown: Why the Pipeline Matters

Oct 9, 2013• 5

By Suzanne M. Rivera

Much attention has been paid to the government shutdown that started last week. Many of us heard heart-tugging stories on public radio about the NIH closing down new subject enrollment at its “House of Hope,” the clinical trial hospital on the NIH main campus. These stories gave many people the impression that clinical research halted around the country when the federal government failed to approve a Continuing Resolution.

The reality is both less dramatic in the short term and more concerning for the long term. For the most part, federally-funded projects at university campuses and hospitals are continuing as usual (or, the new “usual,” as reduced by sequestration), because the grants already awarded are like I.O.U.s from the government. By and large, university researchers will keep spending on their funded grants, with the knowledge that reimbursement will come once the government re-opens for business. The universities and hospitals are, in a sense, acting like banks that loan the government money while waiting for these expenses to be reimbursed.

Also, many clinical trials are funded by the pharmaceutical industry. So it is not the case that hospitals are closing their doors to research en masse. But the long-term effects of a shutdown will have lasting and compounding effects on our science pipeline. The U.S. federal government is the single largest funder of scientific research at American universities. Each month, thousands of grant proposals are sent to the various federal funding agencies for consideration.

These in turn are filtered and assigned to peer review committees. The whole process of review, scoring, and funding approval typically takes months, sometimes more than a year.

How the Federal Government Shutdown Is Hurting Healthcare: Agency by Agency

Oct 2, 2013• 1

By THCBist

The shutdown could not stop the rollout of the state and federal exchanges.

That’s because the Obama administration, sensing a political fight in the offing with Republicans, wisely prepaid the bill for the insurance exchanges and other key components of the rollout.

On the other hand, the fiscal standoff is having a very real impact on the infrastructure that supports healthcare across the United States. Agencies from the Centers for Disease and Control to the National Institutes of Health have seen their money turned off. Others have seen their staffing levels sharply reduced with non-essential employees furloughed.

It doesn’t take a wild imagination to imagine potential deadly consequences if something goes wrong. If for example, flu season strikes early or a drug recall is needed. Much of the pain will be felt over time. As the shutdown drags on, you can expect problems that are brewing under the surface to become much more visible …

Here’s a review of what’s happening:

Centers For Disease Control and Prevention
Funding for monitoring of disease outbreaks turned off. Lab operations sharply scaled back. 24/7 operations center to remain online. With some scientists predicting a severe 2013-2014 flu season, this is cause for concern …

National Institutes For Health
Enrollment in new clinical trials suspended, impacting thousands of patients suffering from serious diseases. No action on grant proposals. Minimal support for ongoing protocols.

Food and Drug Administration
Food safety inspections sharply cut back. Monitoring of imports eliminated. Oversight of production facilities curtailed, again potentially an issue with flu season on the way.The good news? Because drug approvals are funded by industry “user-fees” FDA approvals of new drugs will continue.

Centers For Medicare and Medicaid Services
Key ACA related operations intact. The bad news for docs and patients – claims and payment processing expected to continue but with slower service than usual. With purse strings tight, this is likely to become more of a problem as shutdown drags on. In the unlikely event that a shutdown continues for more than a month, the impact on physician practices could be much more serious.

Cleveland Clinic Trial of Breast Cancer Vaccine Moves Forward

Sep 21, 2013• 13

By Kathleen T. Ruddy, MD

A preventive breast cancer vaccine developed by Professor Vincent Tuohy of the Cleveland Clinic will be brought forward to the FDA for permission to begin clinical trials to see if it is safe and effective for use in women.

The vaccine was shown to be completely safe and 100% effective in preventing breast cancer in three animal models, (see study in Nature Medicine), and was also found to slow the growth of tumors that had already formed. The vaccine is especially powerful in inhibiting the growth of triple-negative breast cancer, the most aggressive form of the disease with the lowest survival rate.

Triple-negative breast cancer lacks estrogen, progesterone and Her2 receptors. It occurs in approximately 15% of cases is the kind of breast cancer most common in women who carry a BRCA mutation.

The initial clinical trials, called Phase I studies, will be conducted in two groups of volunteers, women with triple-negative breast cancer who have completed their treatment and are free of disease, and women who will be vaccinated shortly before undergoing bilateral prophylactic mastectomy (typically these are women like Angelina Jolie with BRCA mutations who elect to remove their breasts to lower their risk for cancer.)

The first group of women will be studied to determine the dose and effectiveness of the vaccine; the second will be studied to make sure the vaccine does not trigger an untoward immune response in breast tissue.

The vaccine targets an unique protein normally made only by women who are breastfeeding, alpha lactalbumin (ALA). In the 12 years Tuohy spent developing and researching his vaccine, he discovered that the majority of breast tumors express, or make, ALA. Priming the immune system with a vaccine so that it attacks any cell that makes ALA is the method by which Tuohy’s vaccine works.

Because the vaccine targets ALA, a protein necessary for successful lactation in healthy women, the vaccine would not be appropriate for use in women who are still in their childbearing years.

However, the majority of women diagnosed with breast cancer in the United States and other western countries are post-menopausal: at least 60% of the cases in the United States occur in women over 55; thus, Tuohy’s vaccine holds great potential as a preventive vaccine for the majority of women.

When Opting Out Is Not an Option

Aug 31, 2013

By Katherine Chretien, MD

Henrietta Lacks did not give researchers permission to take her cancer cells and study them. After she died in 1951, her family was not asked permission as her immortalized cells were used in countless laboratories. This month, the National Institutes of Health finally took a step in righting that wrong, announcing that the Lacks family would help decide who can access Henrietta’s DNA.

Today, getting a patient’s permission, often in writing, is standard in experimental medical research. Well, not always. Currently, there are at least nine ongoing studies involving 62 U.S. cities and towns with a combined population of more than 45 million that do not involve getting permission. They take place during emergencies, such as when ambulances arrive at an accident where patients are too injured to give permission.

For example, imagine this scenario based on a recent study sponsored by the University of Washington. You are involved in a car accident. Paramedics find you bleeding severely. They give you fluids to keep your blood pressure up, but they intentionally give you a bag of fluid that is smaller than the standard. Then they monitor your medical outcome and compare it with patients who received the larger amount of fluids. During the emergency, neither you nor your family know about the study.

Vital research

Research on medical emergencies is vital in determining how to care for people with life-threatening injuries because we often do not have proof that standard methods are the best. People involved should be told that is how their records are being used.

In 1996, the Department of Health and Human Services and the Food and Drug Administration passed regulations allowing research about emergency treatment to occur without permission. For a study to qualify, patients need to have a life-threatening condition, current standards of care must be unproven or performing poorly, and obtaining permission must not be feasible (such as an unconscious patient or a patient whose condition does not allow time for informed consent).

What If Doctors Had Instant Access to All Medical Research?

Apr 7, 2013• 1

By Stanford Med

We are asking doctors to help us study what access to all medical research would mean for their practice. To study the value of such access, we are providing physicians who participate in this Stanford University Public Access Study with eleven (11) months of complete access to virtually all medical journals, as well as to an evidence-based clinical decision-support service.

Participating physicians will have free, one-click access to this vast body of research on their computer or tablet, whenever and wherever they are online. The study is intended to inform current discussions and legislation on the state of public and professional access to federally funded medical research.

Demands on Participant: Participants must be a physician licensed to practice in the United States. Data will be collected on participants’ use of research, with selected participants asked to participate in a 30-minute confidential interview. As a control measure, participants are given an extra month of the evidence-based clinical decision-support service, either prior or following the eleven months of access to the research literature.

To learn more and/or to begin immediate participation (after providing informed consent) in the Public Access Study, follow this link: http://nihpublic.stanford.edu/.

The principal investigator of the Public Access Study is John Willinsky, Khosla Family Professor, Stanford University, Stanford CA; jo************@******rd.edu.

Can Personalized Care Survive ObamaCare’s Assembly Line Medicine?

Oct 1, 2012• 7

By John Goodman

Previously, I wrote about some wondrous developments that are taking place in medical science. Implantable or attachable devices already exist — or soon will exist — that can monitor the conditions of diabetics, asthmatics, heart patients and patients with numerous other chronic conditions. These devices will allow patients and doctors to modify therapeutic regimes and tailor treatments to individual needs and responses. Genetic testing is reaching the point where patients can be directed to take certain drugs or avoid other drugs, based solely on the patient’s own genes.

Almost all HIV treatment these days involves therapy cocktails tailored for each individual patient. The FDA has approved a breast cancer drug only for women with a particular genetic makeup. Patients are being advised to steer clear of an ADHD drug and certain blood thinners if they have particular genetic variations.

We are entering the age of personalized medicine, where the therapy that’s best for you will be based on your physiology and genetic makeup — and may not be right for any other patient.

Yet standing in the way of this boundless potential is an Obama administration whose entire approach to health reform revolves around the idea that patients are not unique and that bureaucrats can develop standardized treatments that will apply to almost everybody with a given condition. When former White House health adviser Ezekiel Emanuel told CNN recently that “personalized medicine is a myth,” he was fully reflecting the worldview of the authors of health reform.

Clinical Trials for Beginners

Jul 16, 2012• 8

By Judy Stone, MD

Have you ever wondered about what goes on behind the scenes—how new drugs are magically produced and brought forth? We’ll continue to take the mystery out of clinical research and drug development and to provide background information so that both patients and physicians can make more informed decisions about whether they wish to participate in clinical trials or not.

Why care?

To develop a medicine, from the time of discovery of the chemical until it reaches your drug store, takes an average of 12-15 years and the participation of thousands of volunteers in the process of clinical trials (Fig 1).

Very few people participate in clinical trials—it is even less than 5% for patients with cancer—due to lack of awareness or knowledge about the process. We’ll go into detail about how drugs are developed in later posts.

An inadequate number of volunteers is one of the major bottlenecks in drug development, delaying the product’s release and usefulness to the public. Of course, many people may suffer or even die during this wait, if they have an illness that is not yet otherwise treatable. So if you want new medicines, learn about—and decide if you wish to participate in—the process. I have, as a volunteer subject, researcher, and advocate.Continue reading…

Calculating Risk

Jun 12, 2012• 1

By Linnea Duff

Thursday I traversed the frozen surface of the pond for perhaps the last time this season. The ice is thinning quickly. I had on my rubber boots and stayed what I felt to be a safe distance from shore: should I break through, the water would not be over my head. I got some fantastic photos and considered the little adventure a success. However, over dinner that evening when I mentioned that I’d been on the pond earlier, David and Peter were furious. Peter wouldn’t calm down until I promised I wouldn’t go out again.

I have always considered fear the enemy; something to conquer and overcome and I’ve had a lot of practice. Being risk adverse and scrappy has been an asset now that I have lung cancer. As a participant in a phase I clinical trial, there is the potential for unforeseen and possibly life threatening side effects of treatment itself. Before you are given your first dose of an experimental drug, you must read through and sign consent forms which acknowledge this risk. It is something most healthy persons would never do. When you have a terminal illness, it is similar to coming to the edge of a ravine with a tiger on your trail. Between you and safety is a rickety bridge that may or may not support your weight. However, even chancy passage is an easy decision when the alternative is certain death.

Drug Data Shouldn’t Be Secret

May 11, 2012• 9

By Peter Doshi and Tom Jefferson

In the fall of 2009, at the height of fears over swine flu, our research group discovered that a majority of clinical trial data for the anti-influenza drug Tamiflu ― data that proved, according to its manufacturer, that the drug reduced the risk of hospitalization, serious complications and transmission ― were missing, unpublished and inaccessible to the research community. From what we could tell from the limited clinical data that had been published in medical journals, the country’s most widely used and heavily stockpiled influenza drug appeared no more effective than aspirin.

After we published this finding in the British Medical Journal at the end of that year, Tamiflu’s manufacturer, Roche, announced that it would release internal reports to back up its claims that the drug was effective in reducing the complications of influenza. Roche promised access to data from 10 clinical trials, 8 of which had not been published a decade after completion, representing more than 4,000 patients from every continent except Antarctica. Independent verification of the data seemed imminent. But more than two years later, and despite repeated requests, we have yet to receive even a single full trial report. Instead, the manufacturer released portions of the reports, most likely a very small percentage of the total pages. (One of us, Tom Jefferson, has been retained as an expert witness in a lawsuit relating to some of these issues.)