Tag: Clinical Trials

Our Guide to Pre-Approval Access to Drugs For Both Doctors & Patients


In April 2016, I published guidance, in the form of a mock case study, on how to access a drug before it has been approved by the FDA—what’s known as pre-approval (or expanded or compassionate) access. This is an updated version of that guidance, reflecting multiple important changes in the pre-approval landscape over the past year. In particular, the FDA rolled out a new, streamlined form for single-patient requests, and Congress passed the 21st Century Cures Act, which, among many other things, mandated that certain pharmaceutical companies provide public information about their pre-approval access policies.

Patients (and physicians) trying to access an unapproved drug outside of a clinical trial can feel as though they’re navigating uncharted waters. Many physicians don’t know that the FDA permits the use of unapproved drugs outside of clinical trials; those who do know often have no idea how to access such drugs for their patients. Those physicians who know about pre-approval access are largely specialists in certain areas—often, oncology or rare diseases—and they are generally self-taught: they didn’t learn about pre-approval access in medical school or in their residencies. Thus, while some physicians have become very accustomed to requesting pre-approval access to drugs, the majority lacks this knowledge. In this essay, I use a fictional case to trace the process for requesting access to an unapproved drug. I hope to explode several myths about the process, especially the beliefs that the FDA is the primary decision-maker in granting access to unapproved drugs and that physicians must spend 100 hours or more completing pre-approval access paperwork.

Imagine you are a physician, and you have a pregnant patient who has tested positive for the Zika virus. She is only mildly ill, but she’s terrified that the virus, which has been linked with microcephaly and other abnormalities, will harm her unborn child. She’s so concerned that she is contemplating an abortion, even though she and her husband have been trying to have a child and were overjoyed to learn she was pregnant.

Continue reading…

Michelle Longmire, CEO Medable

I never ceased to be amazed by how smart young clinicians solve problems that they see. Michelle Longmire was in residency at Stanford working with colleagues building point solutions when she realized that what they needed was an easy platform on which to develop medical grade apps. Her company Medable was the result. Then she realized that the other big market was clinical researchers, who now have access to Apple’s ResearchKit, but need an easy way to build a study without using developers. I interviewed her recently and she built a study for me using Medable’s new Axon product.

Rallying Cry: Cloud and Data First For Pharma

DAN HOUSMANMaybe it is just the shock of being post Labor Day and realizing that summer is fading into the rear view mirror or maybe it was something I ate for breakfast that spurred new hope. But I think that this is the year that the patient centric approach to data in life sciences finally takes off. And along with that launch will come the massive rapid migration to cloud and data lake architectures for pharma data.

Really? Why now you may ask?

Yeah – that’s right. Every group I have been talking to is worried that they are sitting atop a jigsaw puzzle of siloed data resources that can’t be assembled fast enough to meet the needs of business and scientific users. Organizations are thinking that they can’t answer their questions about why drugs work in some patients and not others if they can’t link phenotype and genotype data. Groups can’t look across clinical trials. They can’t look beyond and between clinical trials and EMR data. Progressive safety groups are considering using automation and cognitive computing to lower costs in processing events so they can then look in parallel to expanding sensing new signals into 10X current volumes of data within large real world data sets.Continue reading…

In Silico Medicine

flying cadeuciiCould computers develop the drugs of the future?  The short answer: probably, but not yet.

Computer simulation is a cornerstone in the development and optimization of “mission-critical” elements in industries ranging from aerospace to finance.  Even the smooth functioning of nuclear reactors – where failure would be catastrophic – relies on a computational model called a Virtual Reactor, which allows scientists and engineers to observing the reactor’s real-time response to operating conditions.

The analogous model in medicine – a “virtual human” – doesn’t yet exist.  We still rely on living, breathing animals and humans to test drugs and devices.  Discoveries are made largely by trial and error.  But the age-old approach that led to the discovery of antibiotics, cardiac catheterization, and organ transplantation is becoming increasingly unsustainable.

Continue reading…

Clinical Research Rebooted

Screen Shot 2015-09-03 at 9.27.31 AMThe traditionally conducted clinical trial model requires increasing amounts of time, cost, and resources for both sponsors and sites. In fact, fewer than 10% of clinical trials are completed on time  due to poor patient recruitment, retention and protracted budget negotiations. And since 2008 per-patient, clinical trial costs in the US have risen an average of 70% across all development phases.

In March 2015, however, BLOOMBERG BUSINESS
reported “Stanford University researchers were stunned when they awoke Tuesday 10 March to find that 11,000 people had signed up for a cardiovascular study using Apple Inc.’s ResearchKit, less than 24 hours after the iPhone tool was introduced. ‘To get 10,000 people enrolled in a medical study normally, it would take a year and 50 medical centers around the country’ said Alan Yeung, medical director of Stanford Cardiovascular Health. ‘That’s the power of the phone.”‘


At Scanadu, data collection and clinical studies are key to the development and deployment of our medical devices, and we’re fully aware of the kind of scale and speed and power we’re talking about here. And as a startup developing the next generation of medical devices for consumers, we had to innovate the clinical study process, while bucking the traditional assumptions of how a clinical study should operate.

Continue reading…

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

Screen Shot 2015-03-12 at 12.12.06 PM
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.

Continue reading…

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

Continue reading…

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.

Continue reading…

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.

Continue reading…

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.

Continue reading…


Forgotten Password?