Kids v Cancer

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Before It’s Too Late: Multistakeholder Perspectives on Compassionate Access to Investigational Drugs for Pediatric Patients With Cancer (ASCO Educational Book)

 

Before It’s Too Late: Multistakeholder Perspectives on Compassionate Access to Investigational Drugs for Pediatric Patients With Cancer

Elena Gerasimov, MA, MPH1; Martha Donoghue, MD2; Josh Bilenker, MD3; Tanya Watt, MD4,5; Nancy Goodman, JD1; and Theodore W. Laetsch, MD4,5,6 Show More

Abstract

Patients and their families, physicians, drug companies, and regulatory agencies have common goals: to find effective therapies for life-threatening conditions. In oncology, the lines between clinical research and treatment are often blurred; parents and physicians of patients who have exhausted standard-of-care treatments and cannot participate in a clinical trial are likely to consider seeking compassionate use access to investigational drugs; however, knowledge and perspectives about compassionate use may differ among these groups. There are unique considerations associated with providing compassionate use to children diagnosed with cancer, including evaluation for potential developmental toxicities, the need for pediatric-specific dosing and formulations, informed consent, and, when appropriate, patient assent. Positive impacts of providing access to investigational therapies to children include potential treatment benefits to patients who obtain investigational agents as well as benefits to future patients if data from expanded access support drug development for childhood cancer. Challenges for physicians seeking compassionate use access to investigational drugs for their patients include obtaining the drug sponsor’s agreement to provide the investigational drug as well as lack of knowledge about the process and regulatory requirements. Clinical trials in oncology provide the possibility of therapeutic benefit for pediatric patients; when feasible and warranted, these benefits should also be available to patients on a compassionate use basis outside of trials.

 

PRACTICAL APPLICATIONS

  • Compassionate use can be the best option for patients who seek treatment and cannot participate in a clinical trial and who have no satisfactory therapeutic alternatives.
  • Pediatric oncologists should be knowledgeable about the compassionate use process and prepared to advocate for access on behalf of patients.
  • The FDA has streamlined the process of applying for compassionate use and has created a call center, Project Facilitate, to help guide oncologists through the process.
  • The FDA encourages drug sponsors to provide expanded access to investigational drugs to patients who are unable to enroll in a clinical trial, when feasible and warranted.
  • Compassionate use can produce data that enhance drug development for children.

INTRODUCTION

Access to investigational therapies outside of a clinical trial is known as compassionate use. Some other terms for compassionate use include expanded access, preapproval access, early access, single patient investigational new drug (IND), named patient program, temporary authorization for use, and treatment use. The U.S. Food and Drug Administration (FDA) uses the term “expanded access,” which it defines as “a potential pathway for a patient with an immediately life-threatening or serious disease to gain access to an investigational medical product for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available.”1

Conversations between patients or caregivers and oncologists about compassionate use typically occur in the setting of a life-threatening cancer that has not responded to standard treatment. Patients with cancer are often willing to accept significant risks associated with treatments, especially in life-threatening situations.2 Compassionate use may be considered for patients who do not satisfy eligibility criteria for a clinical trial or who cannot travel to or identify a clinical trial that is accepting patients.

A key difference between compassionate use and clinical trials is therapeutic intent. Although pediatric clinical trials must confer at least a prospect of clinical benefit to participants,3 the main purpose of clinical trials is to conduct research, whereas the primary goal of compassionate use is treatment. However, clinical research4 and compassionate use access have the potential to provide clinical benefit to patients. In addition, although the quality of data derived from compassionate use is generally not equivalent to clinical trial data, information gained from expanded-access programs can influence drug-development decisions for sponsors and support clinical trial data in the regulatory review of new drug applications.

Access to investigational drugs through compassionate use is especially important for pediatric patients, because studies of new drugs are typically conducted first in adults, and relatively few cancer drugs are FDA approved specifically for pediatric patients. Additionally, eligibility criteria exclude children and adolescents from many “adult” clinical trials.

CATEGORIES OF EXPANDED ACCESS

The FDA divides expanded use programs into three categories based on the number of patients (Table 1):

  1. Individual patient (single patient IND). Requests for an individual patient, including emergency use, are the most commonly submitted requests. In 2018, the FDA received 1,576 new individual patient IND requests, including 528 for emergency use,5 and 102 IND protocols.6 Data from 2014 show that 37% of requests received were for oncology (20%) and hematology (17%) products.5,7 Most commonly, the treating physician agrees to serve as a sponsor/investigator for purposes of administering a compassionate use drug and, thus, accepts responsibility for the new IND.8 However, it is also possible for pharmaceutical companies to submit a single patient protocol as an amendment to their existing commercial IND.
  2. Intermediate-size population. This category of expanded access is used when a sponsor has or anticipates that it will receive multiple expanded access requests, but a treatment protocol or IND is not warranted. The FDA recommends that sponsors consider opening an intermediate-sized expanded-access protocol or IND9 when it is expected that more than 10 patients will receive compassionate use access to an investigational drug. Intermediate expanded access is not used frequently; in 2018, the FDA received 20 intermediate-size IND requests and 19 IND protocols.6
  3. Widespread treatment use (or treatment IND or protocol). This category provides access for large numbers of patients, often for late-stage products during the period between the completion of pivotal trials and drug approval.10,11 Treatment protocols and INDs are sponsored by the commercial developer of the investigational drug. Widespread treatment use INDs are relatively uncommon, and single patient INDs are the most common method for obtaining compassionate use access for investigational drugs that are in early-stage development.6

For full text, please read the article on ASCO website.