“WHY hasn't the Food and Drug Administration (FDA) approved any products for the prevention of chronic pain following surgery?” You have probably heard this question asked in any number of settings, and perhaps you have asked it yourself. There is a clear need for analgesic drug products that would prevent the development of chronic pain after certain surgical procedures such as mastectomy and thoracotomy. Why is the FDA holding up development of drug products that could prevent needless suffering? If only it were that simple. The reality is that the agency has not received a single marketing application for a drug product that is intended to prevent chronic pain, and we have received less than a handful of investigative applications for this use.
As a regulatory body, the FDA is tasked with providing guidance to industry and investigators on how to develop drug products for future marketing. Without any experience with successful development programs or clinical studies, and when there is a paucity of data in the medical literature, any advice we might provide would be speculative and possibly result in the expenditure of precious resources on a failed development program. There remain many crucial unknowns regarding the development of drugs to prevent postoperative analgesia. We do not know what an appropriate clinical trial design should look like to provide an accurate and efficient assessment of chronic pain prevention after surgery. We have no data to support recommendations regarding the appropriate patient populations to be studied, the proper length of treatment, the validity of specific study endpoints, or the best methodologies for addressing confounding variables.
As a public health agency, FDA is tasked with finding ways to facilitate analgesic drug development, not just for preventative analgesia but to address the broader problem of inadequately treated pain in the United States. The most commonly used analgesics in the United States are opioids, nonsteroidal antiinflammatory drugs, and acetaminophen. Each of these drug classes is burdened with its own set of serious potential toxicities and, for the opioids specifically, there are additional concerns related to the growing public health crisis of misuse and abuse. The development of novel analgesic drug products is not just a good idea, it is an imperative that all stakeholders in the community should support.
In an effort to address the unmet need for novel analgesic drug products, the agency has embarked on a project under our critical path initiative*intended to move the field forward and to help facilitate the development of products in this area. The Analgesic Clinical Trial Innovations, Opportunities, and Networks (ACTION) initiative is being designed as a public–private partnership (PPP) for two key purposes. First, to bring together the many experts from academic, government, and private organizations with the well-defined goal of sharing data, best practices, and innovative thinking. Second, under the auspices of the ACTION initiative, it is anticipated that these stakeholders will leverage their resources (data, infrastructure, and funds) and expertise to foster dialog and develop specific projects that will add to the body of information so that analgesic drug development can be moved forward in an expedited and efficient manner. This concept of strategic partnerships is not a novel approach at FDA.1Furthermore, this mechanism has been successfully used in several different industries in which no one partner possesses all the resources or the expertise to move an entire field forward. One PPP of particular interest to the anesthesia field is the Safety of Key Inhaled and Intravenous Drugs in Pediatrics (SAFEKIDS) initiative. The SAFEKIDS initiative was developed to address the unclear clinical relevance of the neurotoxicity seen in juvenile animals exposed to general anesthetic and sedative drugs. Under the SAFEKIDS initiative, the FDA has partnered with the International Anesthesia Research Society to form the SAFEKIDS PPP. Under this SAFEKIDS PPP, FDA and the International Anesthesia Research Society will invite participation from numerous stakeholders, including industry, professional organizations, academia, and patient advocacy groups, to join forces and help bridge the scientific and clinical gaps in addressing whether there are safety issues associated with the use of anesthesia and sedatives in children. As a first step in this process, FDA has partnered with a number of academic researchers to conduct some preliminary clinical and preclinical studies. In November 2009, the International Anesthesia Research Society and FDA jointly sponsored the first SAFEKIDS workshop, which brought together an international group of academic experts, industry representatives, representatives from the National Institutes of Health, and other stakeholders. The objectives of this workshop were multifold: to provide a venue for the presentation of initial reports from the investigators funded by FDA, to present the business model for and the key elements of the SAFEKIDS PPP, and to receive feedback from the stakeholder community regarding additional studies that are still needed. As part of this workshop, FDA solicited feedback on the overall direction of this initiative as well and encouraged others to join in this effort directed toward the safe use of anesthetics and sedatives in children.
FDA has partnered with a number of entities under the ACTION initiative. One of these initiatives was specifically undertaken to develop a scientifically sound and clinically relevant protocol to study analgesic drugs for the prevention of postoperative chronic pain. FDA and the University of Pennsylvania held a full-day workshop supported by that contract in September of this year, which brought together a group of academics and industry representatives from the United States and other countries who are thought leaders in the study of preventative analgesia. The editorials focusing on preventing chronic postoperative pain in this issue of Anesthesiology are one of the outcomes of that workshop. The other outcome will be a protocol that we hope will provide the basis for future successful studies of analgesic drug products targeted for the prevention of chronic pain after surgery.
The merits of strategic collaborations and PPPs have long been recognized because of their win-win capabilities—creating intellectual matrices and information networks in which the whole is greater than the sum of the individual parts. In the current era of shrinking budgets and other scarce resources, partnerships, alliances, and collaborations are a necessary and effective mechanism for advancing multidisciplinary fields, particularly among partners with aligned missions. By effectively leveraging expertise and resources, collaborations promise to serve the needs of multiple stakeholders, deliver immediate value and long-term returns, develop innovative solutions and best practices to minimize risk, and lower overall costs for meeting milestones and delivering results. Under the mechanism of a PPP, the ACTION initiative will seek to advance the development of novel analgesics in an expedited manner for the prevention of chronic pain after surgery and for the treatment of pain in general. We encourage all stakeholders to join this effort by contributing their knowledge and resources toward these important public health goals.
†Division of Anesthesia, Analgesia and Rheumatology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland. firstname.lastname@example.org. ‡Office of the Commissioner, Food and Drug Administration, Rockville, Maryland.