all the information, none of the junk | biotech • healthcare • life sciences

“21st Century Cures” By Year’s End? Its Backers Want More Ideas

Xconomy National — 

If you have an idea to include in the bipartisan initiative known as 21st Century Cures, Fred Upton (R-MI) and Diana DeGette (D-CO) say they are all ears. But speak up quickly: They want to present a bill to the House of Representatives by Memorial Day.

That was the message the two members of Congress provided today at the BIO CEO & Investor Conference in New York. Upton, the chair of the House Energy and Commerce Committee, and DeGette (pictured above), have been convening hearings, discussions, and roundtables around the country to craft legislation that would boost federal support for biomedical research and speed development and approval of new drugs and devices.

The ambitious idea—ambitious for no other reason than its main backers are bipartisan members of Congress—will require far more cooperation across the political aisle, and surely a large amount of funding.

It’s also unfinished, which is why Upton and DeGette asked those in attendance Monday to keep the ideas coming.

“We want your input,” Upton said to the crowd during a chat with DeGette that was hosted by BIO president and CEO Jim Greenwood. “This is not going to be what the bill is going to look like.”

Upton was referring to a roughly 400-page discussion draft that was posted to the Energy and Commerce Committee Website on Jan. 27. (A much shorter summary is here.)

Here are a few of the provisions:

—Even faster approvals for drugs that receive the FDA’s “breakthrough therapy” designation.

—A similar breakthrough designation for medical devices.

—A new regulatory pathway for antibiotics.

—New standards for evaluating surrogate endpoints, which are biological markers that could be used to form the basis for a drug’s approval.

—Easier access experimental, unapproved drugs under “compassionate use” exemptions for seriously ill patients.

Upton said a new document should be out in a few weeks. His goal is to have a bill in front of the House before Memorial Day and on President Obama’s desk by the end of the year. “We really don’t want it to get caught up in the presidential politics of 2016,” he said.

As DeGette explained, backers of 21st Century Cures want to address four broad areas:

1) Integration of patient perspectives into the regulatory process.

2) Modernization of clinical trials. DeGette noted, for instance, that if researchers from institutions in New York and Colorado want to do a research study together, there is a “cumbersome process” in place that renders it “costly and slow.”

3) “Fostering the future” of young scientists. “One thing we’ve heard strongly in forums all around the country is that young scientists are being chilled from going into the profession because they can’t get [National Institutes of Health] grants,” DeGette said, noting how funding for such grants has slowly eroded over time. DeGette and Upton are trying to figure out a way to spur young scientists to continue on.

4) More support for digital medicine.

DeGette also said she hopes to incorporate elements of President Obama’s precision medicine initiative.

Anything linked to the president could be anathema to a certain cadre of Republicans, who now control both houses of Congress. Spending will also be an issue for budget hawks on both sides of the aisle, and so far there’s no estimate of how much 21st Century Cures will cost.

The initiative’s proponents are likely to call for more NIH funding. The NIH’s budget, which was roughly $30 billion for the 2014 fiscal year, has been on the downswing partially due to inflation over the past decade.

DeGette knows the increases are presented will be crucial to winning support in Washington, even if the bill is supposed to be, as Upton said, “nonpartisan” in nature.

“It’s going to be challenging to make all the moving parts work,” DeGette said. “My goal is to have upwards of 400 votes [in the House], and if we really do this right, I think we can have that kind of consensus.”

By posting a comment, you agree to our terms and conditions.

  • This is a great and very much needed opportunity to provide additional input for 21st Century Cures.

    It is widely known that the number of new drugs approved per billion inflation adjusted U.S. dollars has halved every nine years from 1950 to 2010. http://tinyurl.com/Eroom-s-Law

    This decline in productivity has occurred despite previous legislative attempts to improve productivity. Productivity has declined during great advances in science and technology such as decoding genomes.

    Is there good reason to think that http://energycommerce.house.gov/sites/republicans.energycommerce.house.gov/files/114/Analysis/Cures/20150127-Cures-Discussion-Document.pdf will produce different results?

    Although I have not yet been able to examine this long document in detail, the answer appears to be NO.

    “FDA’s evaluation methods have remained largely unchanged over the last half century” (FDA Science Board, FDA Science and Mission at Risk, November, 2007). The first modern Randomized Controlled Trial (RCT) design has been dated back to 1948 – streptomycin for TB. This is just two years before the beginning of data used to document Eroom’s Law.

    Many advances in life science and technology need to be evaluated with RCTs before being approved and marketed to improve the human condition. Might it be that many conventional RCTs are designed to fail?

    YES – many RCTs are designed to fail. This can be stated as both a problem and as an opportunity – the PROBLEM first.

    i) Group averages are used to access causality. This washes out the effects individuality and is antithetical to personalized and precision medicine. This also differs from how clinicians evaluate treatment effects for individual patients.

    ii) Patients often are randomized to different dose groups including placebo as zero dose. This makes it hard to get doses right and raises ethical problems.

    iii) Treatments and their effects are evaluated largely one-by-one. In fact, many patients take more than one drug and any one type of drug has more than one beneficial and harmful effect.

    iv) Important aspects of safety and efficacy are evaluated with different methods. RCTs that focus on efficacy neglect safety. This contributes to avoidable morbidity and mortality.

    v) Many RCTs test hypotheses using change scores with artificial endpoints. Baseline to endpoint change scores are not reliable indicators of treatment effect when there is measurement error and uncontrolled variables. Death is a real endpoint. Blood pressures, laboratory variables, rating scale scores, and measures of mental and physical performance are artificial endpoints.

    These were five aspects of a larger problem.

    The OPPORTUNITY is to conduct many – not all – RCTs as coordinated sets of single-patient or N of 1 RCTs before aggregating up with statistics. Each N of 1 RCT would randomize different doses to different periods of time for each individual, collect time series data about treatment and health, and apply an algorithm to compute benefit and harm scores over time and across response variables for each individual. The same algorithm makes it possible to optimize doses, investigate delay and persistence of response, and avoid safety problems – all starting at the level of each individual. All of these scores are well-suited for statistical analyses when there is more than one individual. These statistical analyses can be used to describe groups, make inferences from samples of individuals to populations, and identify genetic predictors of differential response and dose requirements.

    In short, this approach would provide, largely for the first time, treatment response phenotypes that are reliable, valid, comprehensive of multiple beneficial and harmful treatment effects, and detailed for each individual.

    The same computational algorithm often can provide diagnostic phenotypes that are more objective, reliable, specific, mechanistic, and actionable for each individual.

    Suitable time series data are becoming ubiquitous with sensors and devices used by quantified selfers and in homes and hospitals. The Human Connectome Project provides excellent time series data that is not being used to its full potential to diagnose and improve treatment of neuropsychiatric disorders.

    The first priority of 21st Century Cures, the personalized or precision medicine initiative, the BRAIN Initiative, and the Patient-Centered Outcomes Research Institute should be to further validate this disruptive approach to accelerate prevention, cures, and personalized medicine at an affordable price.