Introduction

To become integrated with most medical oncology groups, a good understanding of clinical trials is necessary, since interventional radiology (IR) is likely to be a key player in the trial, whether it is via obtaining a biopsy, injecting a lesion, or participating in novel therapeutic options. Most medical oncologists, and particularly those associated with universities, are very enthusiastic participants in these trials. It attracts patients to the center and allows both academic and private practices to contribute to research. The multicenter groups such as the Southwest Oncology Group (SWOG), the Cancer and Leukemia Group – B (CALGB), or the Radiation Therapy Oncology Group (RTOG) usually coordinate these activities. It is highly suggested that any IR participation in a clinical trial should entitle the IR to be listed as either a co-investigator or key personnel depending on the level of involvement so that the IR may receive the appropriate level of recognition for their contribution. To perform research under a national institute of health or other government-funded grant, any physician or researcher needs to be registered with the Department of Health and Human Services (DHHS) by completing Form 1571 obtained from the DHHS website. ¹

Drug versus Device Trial

The new treatment must first be determined to be either a drug or a device or a combination treatment. There are separate pathways for a drug or device but a combination therapy, for example, chemotherapy combined with a radiation treatment, must be assigned to a particular center. The device pathway is through the Center for Devices and Radiologic Health (CDRH), while the drug pathway is through the Center for Drug Evaluation and Research (CDER). CDER also oversees the following types of biological therapies:

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  Monoclonal antibodies for in vivo use.

  
  
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  Proteins intended for therapeutic use, including cytokines (e.g., interferons), enzymes (e.g., thrombolytics), and other novel proteins, except for those that are specifically assigned to CBER (e.g., vaccines and blood products). This category includes therapeutic proteins derived from plants, animals, or microorganisms, and recombinant versions of these products.

  
  
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  Immunomodulators (nonvaccine and nonallergenic products intended to treat disease by inhibiting or modifying a pre-existing immune response).

  
  
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  Growth factors, cytokines, and monoclonal antibodies intended to mobilize, stimulate, decrease, or otherwise alter the production of hematopoietic cells in vivo.

Other biologics go through the Center for Biologic Evaluation and Research (CBER) and include the following:

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  Cellular products, including products composed of human, bacterial, or animal cells (such as pancreatic islet cells for transplantation), or from physical parts of those cells (such as whole cells, cell fragments, or other components intended for use as preventative or therapeutic vaccines).

  
  
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  Gene therapy products. Human gene therapy/gene transfer is the administration of nucleic acids, viruses, or genetically engineered microorganisms that mediate their effect by transcription and/or translation of the transferred genetic material, and/or by integrating into the host genome. Cells may be modified in these ways ex vivo for subsequent administration to the recipient, or altered in vivo by gene therapy products administered directly to the recipient.

  
  
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  Vaccines (products intended to induce or increase an antigen-specific immune response for prophylactic or therapeutic immunization, regardless of the composition or method of manufacture).

  
  
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  Allergenic extracts used for the diagnosis and treatment of allergic diseases and allergen patch tests.

  
  
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  Antitoxins, antivenins, and venoms.

  
  
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  Blood, blood components, plasma-derived products (e.g., albumin, immunoglobulins, clotting factors, fibrin sealants, proteinase inhibitors), including recombinant and transgenic versions of plasma derivatives (e.g., clotting factors), blood substitutes, plasma volume expanders, human or animal polyclonal antibody preparations including radiolabeled or conjugated forms, and certain fibrinolytics such as plasma-derived plasmin, and red cell reagents.

A combination product, as defined in 21 CFR § 3.2(e), is a product comprised of any combination of a drug and a device; a biological product and a device; a drug and a biological product; or a drug, a device, and a biological product. The regulatory pathway for these will be assigned to the center for which the primary mode of action is determined. For instance, drug-eluting stents may go through either CDER or CDRH, but the primary mode of action is the stent so it went through CDRH. The Office of Combination Products at the Food and Drug Administration (FDA) makes this determination. Once the pathway is defined, a trial needs to be designed. For FDA approval, an initial trial is put together and discussed with the FDA before it is instituted so that any comments the FDA makes can be considered.