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Tag: Clinical Trials

Apple’s ResearchKit is Not (Yet) Ready For Primetime – But Soon? A Medical Researcher’s Perspective

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I am a clinician and a clinical trialist. Medical research in some form or another (performing it, consuming it, reviewing it, editing it, etc.) occupies much of my time. Therefore, you can imagine my excitement while watching Apple’s product announcement yesterday when they introduced a new open source software platform called ResearchKit. Apple states ResearchKit could:

“revolutionize medical studies, potentially transforming medicine forever”

ResearchKit allows clinical researchers to have data about various diseases collected directly from a study participant’s iPhone (and perhaps other devices in the future — see below). The software is introduced as a solution to several important problems with current clinical studies, such as:

  • limited participation (the software allows everyone to participate; anyone with an iPhone can download a specific app for every study they want to participate in)
  • frequent data entry (patients can enter data as often as required/desired, rather than only at limited opportunities such as hospital or clinic visits)
  • data fidelity (currently-used paper patient “diaries” are prone to entering implausible or impossible values — the iPhone can limit the range of data entered)

Specifically, the website states:

ResearchKit simplifies recruiting and makes it easy for people to sign up for a study no matter where they live in the world. The end result? A much larger and more varied study group, which provides a more useful representation of the population.

This is a bold claim. We’ll see below that it doesn’t yet ring true.

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The Misuse of Meaningful Use, Part II

flying cadeuciiAs a result of the determined efforts by Massachusett’s politicians, businesses, health insurance companies, hospitals, individual physicians and the Massachusetts Medical Society, nearly 100% of patients in Massachusetts now have health insurance. This is something all the healthcare players in Massachusetts can be proud of, and “universal insurance” enjoys broad public support here in Massachusetts

In an attempt to improve healthcare quality and reduce cost, Massachusetts is moving away from the “fee-for-service” system and replacing it with “physician groups” which contract with insurance companies. Most of these contracts include financial incentive/disincentive clauses about “quality” and “cost.” As a result, in Massachusetts, it is now almost impossible for a solo practitioner to obtain a contract directly with one of the state’s largest insurance companies. Almost all contracts are mediated through a local physician organization, such as an IPA, PHO or ACO.

As a result, health insurance companies now have much greater influence over the Massachusetts healthcare industry. These large insurance companies define the terms of the contract and can tell the small or medium-sized hospitals/physician contracting group their contract is a “take it or leave it” proposition. Needless to say, it is impossible for any small or medium-sized hospital/physician contracting group to refuse to accept the insurance contract when their financial viability is predicated on having access to the insurance company’s patient panel.

Originally Certified EMRs and Meaningful Use policies were created so as to provide the financially incentive to encourage primary care physicians to adopt electronic medical record programs and then use these electronic medical record programs according to specified “meaningful use” mandates. It was the hope that the appropriate use of EMRs would improve the quality or reduce the cost of healthcare. Since the program’s introduction, Meaningful Use has been expanded to almost every medical specialty and subspecialty, regardless of the appropriateness/relevance.

There has now been a fair amount of data accumulated regarding the effectiveness of electronic medical record programs. Unfortunately, most of the published data is not high quality and the majority of clinical trials are now being funded by the EMR industry. As we have seen with clinical trial sponsored by the pharmaceutical industry, only an irrational person would accept the results of a vendor sponsored EMR trial on face value.

Recently, The Office of the National Coordinator for Health Information Technology (HHS)  asked the RAND corporation to review all EMR data. RAND created the “Health Information Technology: An Updated Systematic Review with a Focus on Meaningful Use Functionalities

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What I Would Do If My Foot Caught Fire

flying cadeuciiI know it seems like the obvious choice, but I would not run a randomized clinical trial.

I have recently lamented the pernicious influence, within my domain of public health practice, of hyperbolic headlines proclaiming “this,” followed unfailingly by equally and oppositely hyperbolic headlines reactively proclaiming “that.”

But we are obligated to acknowledge that there are, generally, research studies underlying the headlines, however extreme the pop culture distortions of the actual findings. So to some extent, the problem originates before ever the headlines are a gleam in an editor’s eye, with our expectant anticipation of the next clinical trial, and the next, and the next.

By all means, bring on the clinical trials! They serve us well. They advance the human condition. I run a clinical research lab — my career is devoted to just such trials.

But still, I wouldn’t conduct one if my foot caught fire.

Of course, there is a very good case for running such a study, as many vitally important questions about the right response to a foot on fire are at present unanswered. What, for instance, would be the ideal volume of water? Should it be hard water, or soft? Fluoridated, or not? A controlled trial is very tempting to address each of these.

The vessel is even more vexing. What would be the best kind of bucket? What size should it be? What color should the bucket be, what composition, and what’s the ideal kind of handle? I think the variations here are the basis for an entire research career.

Perhaps the notion of running randomized, double-blind, controlled intervention trials to determine the right response to a foot on fire seems silly to you. But if so, you must be suggesting that science does not preclude sense.

That’s rather radical thinking in some quarters.

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

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.

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The Government Shutdown: Why the Pipeline Matters

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.

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

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.

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Cleveland Clinic Trial of Breast Cancer Vaccine Moves Forward

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.

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When Opting Out Is Not an Option

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 conditioncurrent 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).

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What If Doctors Had Instant Access to All Medical Research?

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; john.willinsky@stanford.edu.

Can Personalized Care Survive ObamaCare’s Assembly Line Medicine?

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.

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