Tag: FDA

Surrogate End Points Ain’t all that Bad

Aug 9, 2018• 4

By CHADI NABHAN MD MBA

Life is busy, yet we somehow find time to stay engaged on social media, remain engrossed in the 24/7 news cycle, and continue our futile efforts to resist clickbait. While social media can allow us to mindlessly scroll through feeds, it also provides an avenue to provoke vigorous dialogue, however diverse, controversial, or even rooted in unfettered biases. These exchanges have served as the primordial soup for a virtual friend or foe-ships. Tense and argumentative Twitter exchanges are especially entertaining given the challenges in justifying a position in fewer than 280 characters. Thus, tweetorials have emerged to explain a point of view via a thread of comments since it is not always easy to do so in 1 or 2 tweets. The longer the tweetorial, the more heated the debate. What I am trying to get at here, somewhat obtusely, is the concept of surrogates.

I have already suggested a surrogate. Length of a tweetorial is a surrogate for degree of controversy of the topic. Meaning, length is a surrogate, a proxy. We are surrounded by surrogates. Longer wait lines at restaurants and bars imply a hipper joint or tastier menu. My child being extra nice to me is a surrogate for him wanting more time on electronics. Not a day goes by without folks arguing about surrogate endpoints. I wanted to dig deeper into surrogates and since I am a physician, I’m focusing on surrogates in medicine. Apologies to those who thought I would be discussing restaurants or exotic trips.

I want to make sure my definition of surrogates is accurate: Merriam-Webster dictionary for enlightenment. The first use of the word “surrogate” was in 1533, B.T. (“Before Twitter”). A surrogate is defined as “one appointed to act in place of another” or “one that serves as a substitute”. We use surrogate endpoints in clinical trials as a substitute for other end points.

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

Sep 6, 2017• 1

By ALISON-BATEMAN HOUSE

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.

The “21st Century Cures” Draft Bill: A Step Away From Transparency

May 18, 2015• 1

By NIAM YARAGHI

There is optimism that Congress will soon pass the 21^st Century Cures bill. The draft bill proposed by the House Energy and Commerce Committee aims to foster medical innovation by streamlining the FDA regulatory process and increasing NIH research funding by $10 billion. The draft bill has overwhelming bipartisan support and will benefit patients, medical researchers and pharmaceutical companies. However, it also includes a passage, which aims to amend the Sunshine Act and exempt pharmaceutical companies from reporting the payments they make to physicians for continued medical education (CME) programs. The supporters of this change argue that physicians learn about the latest developments in medical science through CME programs and that requiring the disclosure of these payments would discourage pharmaceutical companies from financially supporting educational programs. Ultimately they believe it could inhibit the diffusion of medical innovation among doctors.

I took a look at the data released by CMS on the financial transactions between the pharmaceutical companies and individual physicians. In the last five months of 2013, more than $120 million were paid to physicians who participated (as faculty or speakers) in CME programs. The payments constitute 26 percent of the total financial transactions between pharma and individual physicians. The proposed change essentially allows pharmaceutical companies to hide more than a quarter of their payments to physicians. Exempting the pharmaceutical companies from reporting the largest part of their financial relationship with doctors will not help to foster medical education, rather it will add to current suspicions about the unjustified impact of such payments on the drugs that physicians prescribe to their patients.

If CME programs legitimately increase the awareness of physicians about the latest medical innovations and provide them with unbiased information about new drugs, then both pharmaceutical companies and those physicians who serve as speakers and faculties of such programs should be extremely proud of their role as champions of innovation and envoys of the latest knowledge in the medical community. If that is the case, one would wonder why they wouldn’t embrace and support the efforts that shed light on their noble role.

Patients heavily rely on the recommendations of their doctors to make any kind of decision regarding their health and thus have the right to be informed about the possibility that their doctors have a conflict of interest. Congress should refrain from amending the Sunshine Act and avoid jeopardizing the patients’ right to have access to information.

Niam Yaraghi is a fellow at the Brookings Institute Center For Technology Innovation. His posts appear regularly on THCB and on the Brookings Institute Tech Talk blog, where this post first appeared. This post also appeared as an opinion column on the US News and World Report site.

Those New Neighbors

Sep 16, 2014• 3

By DANIEL GARRETT

Look at who is entering the New Health Economy: Amazon, with digital health applications; Intel, with a home health gateway; Google, with a fit platform, not to mention the news out of Cupertino last week.

Why? According to the 2013 PwC Global Innovation Survey, nearly half of drug and device companies are focusing on traditional product innovation rather than on breaking their efficacy and safety mold. And the stakes are high: As patients become value-seeking consumers, they want quick and easy technology connections to their health source.

It appears that the biggest barrier to transforming traditional healthcare business is culture. Most (89%) of the drug and device CEOs surveyed by PwC view technological advances as the global trend to follow. Yet three-quarters of these executives cite an inability to grasp new information technologies.

Many of these firms invested heavily in social media in 2012 and 2013, but then retreated, possibly awaiting further guidance from the FDA on what is acceptable conduct for “socializing” with consumers.

In fact, the FDA released draft guidance this spring outlining rules for interactive promotional media, including blogs, social networking sites, online patient forums, and podcasts. Some companies, such as Qu Biologics, already use social media to enhance trial recruitment. Companies can scan social media for information about adverse events related to their products. A recent study showed that social media had three times more adverse-event reports for 23 commonly used prescription medications than the FDA did during the same time period.

Any cultural transformation should begin at home. Although drug and device companies say they value social media as an important accelerator of innovation, the evidence is scant on how these firms use technology to promote internal communications that can better connect employees across traditional silos—from R&D to commercial business units.

Are Federal Regulations Stifling Disruptive Healthcare Technologies in the US?

Aug 28, 2014• 8

By TIM MALIYIL

In the past few years, we’ve seen headline after headline marveling at the advancements of medical technology. From wearable tech and micro sensors to 3D printing and health-oriented apps, it’s evident that technology and medicine have merged into an industry that’s pushing healthcare to a new level.

Yet many in the health tech industry are also voicing concerns about government regulators and their standards for healthcare technology. Some have even gone as far as accusing the FDA of “stifling” the creativity of healthcare tech and hindering the value these devices and apps could bring to the public.

In early 2014, legislation was introduced in an attempt to redesign the regulatory framework for certain types of technologies and lessen the FDA’s control over this growing industry. But are the FDA’s standards and actions so bad?

I’m in the tech field myself, and while I’ve heard many arguments against the FDA’s regulations, I strongly feel that it’s completely within its rights as a regulatory agency to place limits on medical technology. The FDA’s standards are put in place to protect consumers and to correct disingenuous manufacturer claims — an alarmingly frequent trend in today’s digital world.

Pseudo Innovation

Jul 31, 2014• 5

By DONALD LIGHT

Few people know that new prescription drugs have a 1 in 5 chance of causing serious reactions after they have been approved. That is why expert physicians recommend not taking new drugs for at least five years unless patients have first tried better-established options and need to. Faster reviews advocated by the industry-funded public regulators increase the risk of serious harm to 1 in 3. Yet most drugs they approve are found to have few offsetting clinical advantages over existing ones.

Systematic reviews of hospital charts by expert teams have found that even properly prescribed drugs (aside from misprescribing, overdosing, or self-prescribing) cause about 1.9 million hospitalizations a year. Another 840,000 hospitalized patients given drugs have serious adverse reactions for a total of 2.74 million. Further, the expert teams attributed as many deaths to the drugs as people who die from stroke. A policy review done at the Edmond J. Safra Center for Ethics at Harvard University concluded that prescription drugs are tied with stroke as the 4th leading cause of death in the United States. The European Commission estimates that adverse reactions from prescription drugs cause 200,000 deaths; so together, about 328,000 patients in the US and Europe die from prescription drugs each year. The FDA does not acknowledge these facts and instead gathers a small fraction of the cases.

Perhaps this is “the price of progress”? For example, about 170 million Americans take prescription drugs, and many benefit from them. For some, drugs keep them alive. If we suppose they all benefit, then 2.7 million people have a severe reactions, it’s only about 1.5 percent – the price of progress?

However, independent reviews over the past 35 years have found that only 11-15 percent of newly approved drugs have significant clinical advantages over existing, better-known drugs. While these contribute to the large medicine chest of effective drugs developed over the decades, the 85-89 percent with little or no clinical advantage flood the market. Of the additional $70 billion spent on drugs since 2000 in the U.S. (and another $70 billion abroad), about four-fifths has been spent on purchasing these minor new variations rather than on the really innovative drugs.

In a recent decade, independent reviewers concluded that only 8 percent of 946 new products were clinically superior, down from 11-15 percent in previous decades. (See Figure) Only 2 were breakthroughs and another 13 represented a real therapeutic advance.

Spokesmen for the pharmaceutical industry point out that therapeutically similar drugs have advantages. First, physicians need some choice within a therapeutic class because some patients do not respond well to a given drug. This is true, but after about three choices, there is little evidence to justify a 4th , 5th, or 6th in a class.

What’s the Value of a Cancer Cure?

Jun 21, 2014• 24

By Cyndy Nayer and Leonard Kish

When CMS approved Solvadi, Gilead’s $84,000 drug for hepatitis C, the stakes were raised in drug price wars. Two opposing forces, one, a financial push toward lower costs came up against an opposing force of public sentiment. The FDA’s goal of getting 90% of patients moved from costly branded prescriptions to generics met with an an large outcry in social and traditional media for providing the best available care, rallying around the story of a patient. The wave of sentiment seems to have won over CMS.

Granted, CMS was likely considering the reversal in its policy on Solvadi, but it was the May 12^th coverage by the Kaiser Family Foundation and NPR of the patient who was denied treatment, and the amplification across social media that turned the tide toward coverage.

Solvadi had not been approved by the patient’s prescription drug carrier, so physicians lobbied CMS for coverage of Solvadi and the life of the patient. Solvadi appears to cure liver cancer in 90% of the patients who take it as recommended. CMS agreed. As a single payer, they have the incentive to balance drug costs and benefits with other costs and benefits, and new therapies often win the fight for coverage.

Getting Covered: The decision to pay for drug combinations is often quicker than FDA approval of the drug combinations

Objective health policy observers such as KFF note that in the early days of successful antiviral drug treatment for HIV, payers allowed doctors to “mix and match” medications in “off-label” or unapproved combinations as they thought best. Medicare is often slow to approve the physician-driven cocktails, so getting CMS to adopt the strategy was a win for many very sick people in this country, as it sets a precedent for “exceptions.”

One doctor at Beth Israel Health System in Boston has a trial that has shown that combining Solvadi with another high-cost treatment, Olysio (by Janssen, cost $66,000 for a course of treatment) resulted in 90-100% cure rate.

The CMS statement in this case noted that that “the new policy will apply broadly to hepatitis C patients whose doctors prescribe the combined use of the two drugs because they meet certain criteria laid out in January by the Infectious Diseases Society of America and the American Association for the Study of Liver Diseases.” Those guidelines recommend the combined use of the two drugs in patients with advanced liver disease who have failed to be cured by earlier drug regimens – even though the FDA has not yet approved the combination—because Medicare guidelines say a patient must have access to a therapy if his or her condition warrants it.

Health IT: The Coming Regulation

Apr 14, 2014• 4

By Andy Oram

The Food and Drug Administration has spent decades refining its processes for approving drugs and devices (and is still refining them), so what would happen if they extended their scope to the exploding health software industry?

The FDA, and its parent organization, the Department of Health and Human Services, are facing an unpleasant and politically difficult choice.

Sticking regulatory fences into the fertile plains of software development and low-cost devices will arouse its untamed denizens, who are already lobbying Congress to warn the FDA about overreaching. But to abandon the field is to leave patients and regular consumers unprotected. This is the context in which the Food and Drug Administration, the Office of National Coordinator, after consultation with outside stakeholders, released a recent report on Health IT.

I myself was encouraged by the report. It brings together a number of initiatives that have received little attention and, just by publicizing the issues, places us one step closer to a quality program. Particular aspects that pleased me are:

The suggestion that quality programs should start to look at electronic health records (p. 8). EHRs have been certified by various bodies, but usually just to check off boxes and declare that the systems comply with regulations–neither the quality of their user interfaces nor the quality of their implementations have been questioned. Reportedly, the FDA considered “safety and quality standards” for electronic health records in 2010 but couldn’t get them adopted. It also checks certain forms of clinical decision support, but only if they are built into a regulated device. The current HHS report refers back to aspirational documents such as a Health Information Technology Patient Safety Action & Surveillance Plan and a set of guidelines on the safety of EHRs.
A call for transparent reporting and sharing of errors, including the removal of “disincentives to transparent reporting”–i.e., legal threats by vendors (p. 25). Error reporting is clearly a part of the “environment of learning and continual improvement” I mentioned earlier. A regulation subgroup stated the need most starkly: “It is essential to improve adverse events reporting, and to enable timely and broader public access to safety and performance data.” Vague talk of a Health IT Safety Center (p. 4, pp. 14-15) unfortunately seems to stop with education, lacking enforcement. I distinctly disagree with the assessment of two commentators who compared the Health IT Safety Center to the National Transportation Safety Board and assigned it some potential power. However, I will ask ONC and FDA for clarification.
A recognition that software is part of a larger workflow and social system, that designing it to meet people’s needs is important, and that all stakeholders should have both a say in software development and a responsibility to use it properly.

Don’t imagine that the FDA is unused to regulating software. For quite some time they have instituted practices for the software used in some medical devices , and have tried to keep them up-to-date.

A waterfall-like process of risk assessment and testing called computer system validation has long been required for pharma and devices.

One Libertarian’s Dilemma: Genetic Testing or the FDA

Jan 10, 2014• 10

By Saurabh Jha, MD

An advantage astrologers have over genetic testing is that the prediction of astrologers are personally verifiable. An astrologer once emphatically stated that I had no chance of a career in international cricket or Bollywood. So far both claims have turned out to be remarkably accurate.

How does one personally verify a “12.5 %” increased chance of lung cancer, the sort of number the vendor for genetic testing 23andMe produces? If one develops lung cancer how would one know that the chances were indeed 12.5 %, not 6.25 % or 25 %?

We die only once. Whether one ends up with lung cancer or doesn’t, the veracity of the claim can be made only empirically. Meaning we need to see how many develop lung cancer out of 10, 000 people just like us.

Yet there is an element of scientific precision in the number, augmented by the decimal point. And it is precisely because genetic testing tends towards science not metaphysics that it falls within the dominion of the Food and Drug Administration (FDA). FDA does not regulate palm readers.

FDA has asked 23andMe to stop sales of its genomic testing.

As a libertarian seeped in the Austrian school of Economics, I am generally disposed against regulations. I also share the sentiments of the monetarist Milton Friedman that the true costs of the FDA must also include the treatment opportunities foregone in their lengthy review process.

So it hurts me to be somewhat sympathetic of FDA’s stance on 23andMe, even as I think an outright ban was a tad harsh.