“Fixing” clinical trials and improving medical research

“Fixing” clinical trials and improving medical research – The House of

Representatives’ 21st Century Cures Act.


In July 2015, the US House of Representatives passed HR 6, better known as the 21st Century Cures Act. The Act is ambitious – its text is over 360 pages long and it contains four wide-ranging titles. According to its sponsors, the Act would overhaul medical research funding, improve and streamline clinical trials for faster device and drug approval, promote certain types of research, aid young investigators, facilitate collaboration and encourage data sharing and mining. The legislation shows very clearly that the House sees the need to change the clinical trials process to make it faster, more responsive to patient needs, and more accepting of new and alternative methods. It also shows that the House wants to make more data available to researchers so that they can better search for future drugs and devices.

This week note takes a snapshot of the first two titles of the 21st Century Cures Act. It is not possible to discuss in any detail all of the provisions of this legislation. Instead, we seek to examine some of the key changes that the Act would make to the clinical trials.

Before we go further, two important caveats should be noted. First, the US Senate has announced that it will NOT consider the Act. The Senate has decided to take up several separate pieces of legislation that are actually similar to parts of the 21st Century Cures Act. Thus, it seems very unlikely that the Act will advance farther than it already has. Second, we are not endorsing or criticizing the Act. We are studying it to get a better idea of the changes that one branch of the US legislature is advocating. This study is useful as part of our team’s effort to better understand key stakeholders and learn about how they approach improving clinical trials.

Title I of the Act is primarily concerned with scientific discovery. Focused mostly on the NIH, it creates an innovation fund for high risk, high reward research, and research by young investigators. It also targets “unmet medical needs,” particularly calling out for more research on biomarkers and precision medicine, and several other things. NIH would be required to create a strategic plan to support these research priorities. This title also gives the director of NIH more authority, allowing him to appoint directors to all of the national research institutes, except the NCI.

Other parts of Title I seek to support new investigators in several ways. First, as mentioned above, a special innovation fund is created. Second, more liberal loan repayment plans are offered. Third, the Act creates a series of Capstone awards for seasoned researchers. This funding could be used to assist in transitioning senior investigators away from research to make room for younger scientists.

The Act would facilitate data sharing and data standardization for clinical trials. The idea behind these provisions is to make it easier for patients to find clinical trials by standardizing patient inclusion and exclusion criteria across all trials in the clinical trials database. It would also create a pilot project to allow the use and analysis of de-identified data from HHS clinical trials beyond the project from which it came. The Act anticipates that researchers could use this database to develop future cures. A similar thrust is made to change the HIPPA law so that a wider group of researchers could have access to de-identified data from HIPPA records.

Title II of the Act, entitled “Development,” contains many of the provisions that would impact clinical trials. It begins by requiring FDA to develop a framework so that patients’ experiences are incorporated into a drug’s benefits and risks analysis. The FDA would have to develop guidance to incorporate patient outcomes data, including patient reported outcomes. The Act continues its movement to expand the techniques available for decision-making by requiring that FDA create a process for qualifying what the Act calls “drug development tools.” Also known as surrogate endpoints, these are tools such as biomarkers that can be used as substitutes for the ultimate health endpoint. These tools would be used to evaluate the safety and/or efficacy of a candidate drug.

Along with these more flexible approaches to evaluate the safety and effectiveness of drugs, the Act would allow for these surrogate endpoints to be used in FDA’s accelerated approval program. According to the Act, a study with the surrogate endpoint could be used to support the claim that the drug is effective. The Act next moves to the concept of “precision medicine.” It would require the HHS to issue precision drug or biological product guidance to assist sponsors in developing such products. In the event that the drug treats a rare condition or life-threatening disease, the Act would allow the sponsor to rely on data previously submitted for a different drug that utilizes the same approach.

Another way in which this Act seeks to change clinical trials is by requiring FDA to issue a guidance document that would help drug sponsors incorporate adaptive designs and Bayesian statistics into clinical trial protocols. These techniques would be used in lieu of, or in addition to, traditional statistical methods and trial designs. The Act also establishes a program for streamlined data review. For treatment of cancer and some additional conditions that HHS designates, if an application has already been approved, the application holder can submit a summary of the clinical data. The House believes that FDA should be able to make decisions based on these data summaries.

For certain patients, expanded access to investigational new drugs is crucial. The Act seeks to eliminate any barriers to such access by requiring manufacturers and/or distributors of investigational new drugs to make publicly available information about the drug on its website. In that way, patients will have access to these expanded access policies. FDA would also have to develop guidance to address adverse event reporting for those using drugs obtained through an expanded access program.

Thinking about these two titles of the 21st Century Cures Act, it is clear that the House is very concerned about the pace of drug development, and the information and technologies that are used (and not used) for decision making. Its bill contains several techniques that are designed to change the pace of drug development. It uses funding mechanisms to spark certain types of research by certain categories of researchers, loosens up the reigns on some important data streams, and makes it easier to utilize surrogate endpoints. Even though this bill is not likely to become law, it offers a chance to see how our House of Representatives classified and suggested ways to change the system that we are now studying.

Paul Locke