Thread by @SteveFDA

For this weekend's #FDA #SUNDAYTWEETORIAL I’m going to talk about what FDA is doing to modernize clinical trials to reduce the cost of drug development, potentially lower drug costs and bring more safe, effective therapies to patients.

FDA’s mission is to both promote and protect public health. For medical products, this means ensuring that they are safe and effective for their intended use. Clinical trials are the primary vehicle for generating the evidence FDA needs to ensure that.

The traditional drug development paradigm calls for 3 clinical trial phases: A small phase 1 tests safety and dosing, phase 2 tests short-term side effects and effectiveness over a range of doses; and the large phase 3 assesses whether the product’s benefits outweigh its risks.

Trials are becoming more costly & complex to administer. It can make drug development more risky, uncertain, time consuming. Overly complex trials can also deter enrollment & delay completion studies so long that findings aren’t relevant for patient care bit.ly/2uQ6sjs

Adding to complexity is “endpoint creep”, with pharmaceutical companies spending $4-6 billion annually on non-core or exploratory endpoints that aren’t related to primary safety or efficacy endpoints. bit.ly/2LK73gb

The result: spiraling drug development costs. One estimate: Rising 145% to an inflation-adjusted $2.8 billion between 2003-2013, a pace that dwarfs other healthcare cost increases. Higher trial costs & complexity impacts market competition & drug pricing bit.ly/2uKax8W

A soon to be published #FDA study found that nearly 5% of novel drugs approved from 1991-2000 had a competitor within 2 years. But it took 5 more years to achieve the same level of competition for drugs approved from 2001-2010. And less competition can mean higher prices.

One reason for the longer development period: It can be difficult to run clinical trials with a second to market drug once therapy is available to treat an unmet need or rare disease. It’s becoming harder and harder to be second.

Modern approaches to designing and conducting clinical trials can address some of these challenges. #FDA is working across our medical product centers to facilitate innovative trial designs and patient-centered endpoints that can make clinical trials more rigorous and efficient.

We’ve been partnering with the nonprofit Clinical Trials Transformation Initiative on the design and conduct of clinical trials that can address these challenges while building on our gold standard. We will not compromise that gold standard one bit. bit.ly/2Ljkocc

And FDA has encouraged several pioneering advances in clinical trial design, including Master Clinical Trial Protocols (MAPs), first used in cancer and now used more widely across FDA, in other therapeutic areas. bit.ly/2JX0pyk.

One MAP, I-SPY 2, compares up to 12 experimental therapies in subgroups of patients with metastatic breast cancer with 10 distinct biomarker signatures. This hub and spoke design uses a common control, reducing the overall # of patients to be recruited and enrolled.

Seamless trials, used in oncology for drugs that might qualify for breakthrough therapy designation, are another novel approach bit.ly/2NQy52K. They compress the traditional 3 trial phases into one large, continuous trial that may be able to speed access for patients.

A lot of time and cost is spent between the starting and stopping of the traditional 3 phases. Continuous trials can save time, lower costs and reduce the number of patients. Look for new guidance soon from #FDA on how developers can conduct these “expansion” trials

Surrogate endpoints are another clinical trial modernization tool. These endpoints are often used when clinical outcomes take a long time to study or when the surrogate’s ability to predict clinical benefit, such as reducing the HIV viral load, is well known.

In cancer, innovative endpoints are facilitating the development of products for both accelerated and traditional approvals putting promising treatments into the hands of high-risk patient years before they would’ve been available using previous endpoints.

FDA just published a list of surrogate endpoints which were the basis of approval or licensure of a drug or biologic product under accelerated or traditional approval bit.ly/2uPQLJ3. It provides useful information for drug developers on endpoints that may be considered.

Although I’ve been focusing on modernizing drug clinical trials, we have efforts underway to modernize medical device clinical trials as well, in part through work we are doing with the Medical Device Innovation Consortium (MDIC) on “virtual patients.”

MDIC is using computer modeling and simulation to create virtual patients. If validated to be like real patients, future device trials may be able to rely on virtual patient information when appropriate, lessening the burden of enrolling real patients and improving on our rigor

FDA is also looking to real world data collected from device registries and electronic health records to answer important premarket and post market questions potentially allowing sponsors to meet evidence needs in less time, at lower cost.

Our aim is simple: innovative, advanced evidence generation to assure the timely availability of safe and effective therapies. Our aim is to improve patient care, and give people the assurance of #FDA's gold standard for safety and efficacy in the most efficient way possible

We need to reduce the burden and cost of advancing care. And we need to make it easier for competition to reach the market once we have a promising new therapy. Our clinical trial advances will ensure that more patients have more safe and effective treatment options available.