The House of Representatives approved the 21st Century Cures Act on July 10th, 2015. The bill, which was drafted by the Energy and Commerce Committee in the House of Representatives, hopes to “accelerate the discovery, development, and delivery of life saving and life improving therapies, and transform the quest for faster cures”. There are around 10,000 diseases and conditions currently known, however, there are only cures and treatments for 500 of them. Furthermore, it can often take decades for new discoveries to be translated into therapies for patients. Thus, the 21st Century Cures Act aims to solve these current problems in the biomedical research field by improving certain aspects of how the National Institute of Health (NIH), Food and Drug Administration (FDA), and Centers for Disease Control and Prevention (CDC) operate.
Proposed Changes in NIH operations:
There are two main changes to NIH operations that the 21st Century Cures Act proposes. First, the bill would create the “Innovation Fund”, which would give the NIH and FDA $1.75 billion per year for 5 years and $110 million per year for 5 years respectively. This money would be used to fund young investigators who currently often have trouble securing grant funding from the NIH for the first time. Young investigators are often where new and innovative scientific ideas come from and it is critical they are funded in order to sustain scientific advancement and push new therapies forward. This fund would also be used to fund high-risk, high-reward research that is challenging but has the potential to lead to huge breakthroughs in science and medicine.
Secondly, the 21st Century Cures Act seeks to enhance how the NIH awards grants. The bill would require the NIH to issue a strategic plan, which would outline NIH’s goals of funding research to decrease the disease burden in the next 5 years. The bill also seeks to increase accountability by one, requiring appointments and terms of Directors of National Research Institutes and Centers and two, the review of certain awards by directors of each institute. Finally, the bill would direct the NIH to research and implement recommendations on how to streamline the grant process for researchers and help reduce administrative burdens.
The main goal of these changes to the operation of NIH is to improve the scientific pipeline, which leads to more cures for diseases. However, these proposed changes do not have the full support of the scientific community. Although scientific societies such as the American Society for Cell Biology (ASCB) are encouraged by a renewed interest in scientific funding at the federal level, there are limitations to the bill. For example, the ASCB has written a letter to the chairs of the Energy and Commerce Committee, Representatives Fred Upton and Diana DeGette, discussing aspects of the bill that the society disagrees with. The main points of the letter are first, that the bill seems to be a way to assign blame when it appears NIH money is not being used to find faster cures. And secondly, changes the grant review process which could determinedly effect how scientific research is funded.
Proposed Changes in FDA operations:
The main goal of the 21st Century Cures Act is to speed up the time it takes for a drug to make it into clinic. In addition to changing the way NIH funds grants, a large part of accelerating the process will come from changes in FDA operations. The bill hopes to incorporate patient perspective into the drug development and regulatory review process, measure success and identify disease earlier through personalized medicine and biomarkers, modernized clinical trials, and remove barriers to increased research collaboration.
Overall, through these changes in FDA regulation congress hopes to get possible “breakthrough” drugs into the hands of patients before they are rigorously tested by the current FDA clinical trial system. Currently, drugs must go through three stages or phases before FDA approval. Phase 1 trials are used to determine that the drug is safe and determine the correct does. Phase 2 trials are larger, and are focused on determining if the drug might have side effects previously unknown. Finally in phase 3 trials, which are the largest, longest, and most expensive trial, the safety and effectiveness of the drug is determined and often compared to the standard of care. The House hopes that the 21st Century Cures Act will allow the FDA to accelerate the approval process of a drug before completing all three phases of a clinical trial. If for example, a drug shows promise based on biomarker, such as the reduction of beta amyloid plaques in the brain of Alzheimer patients, or if patients are advocating for the drug to become approved.
However, many doctors are skeptical of whether the bill will actually lead to more cures and disagree that the FDA should speed up its drug approval process. Recently, three important studies were published that show the dangers of approving drugs before extensive clinical data is known. The first published in Nature Reviews Drug Discovery found that early trials of drugs for diseases, such as multiple sclerosis and depression, had limited predictability in determining whether the drugs were effective. A second study published in the British Medical Journal looked at three Alzheimer’s drugs that started phase 3 trials based on positive preliminary results in earlier phases. Once in phase 3 trials, one of the drugs, semagacestat, which initially showed effectiveness in phases 1 and 2, based on the decrease of beta amyloid plaques in patients, was found to cause skin cancer and worsened patient’s ability to perform activities of daily life, a common measurement of clinical effectiveness of Alzheimer’s drugs. Finally, a third study published in JAMA Internal Medicine argued that biomarkers such as a decrease in tumor burden in patients did not actually correlate with the main clinical goal of cancer drugs: extending the life of patients. Many of these drugs can cost thousands of dollars for the patient and although at first they promise “breakthrough” results, stringent testing is still needed in order to avoid unnecessary spending and unforeseen clinical outcomes.
Overall, most scientists and doctors feel that loosening FDA regulations will not lead to more cures for human disease. Instead, more money needs to be allocated to scientific funding. The better scientists and doctors can understand the mechanisms of diseases the better and more effective drugs that can be created.
Editor: Mary Topalovski