Compassionate Use, Expanded Access, and Off-Trial Use of Treatments for DIPG / DMG

When confronting a diagnosis of DIPG / DMG, clinical trials are often the first resort beyond or concurrent with radiation for treatment options.  Although these trials may not offer a cure, phase 2 and phase 3 trials do offer a limited measure of comfort from life-threatening side effects.  But if these options don’t work, many patients find themselves weighing other options including phase 1 trials or even compassionate use opportunities where little to nothing may be known about the compound being tried.  When this happens, there are several pathways to consider, from standard compassionate access to expanded access and even off-trial usage of drugs.  Below we’ll explore some of the key differences between each, the limitations of each pathway and even a provisional pathway that may also develop in the coming years.

Compassionate Use of DIPG / DMG Treatments

Compassionate use of a therapy or compound is a formal channel recognized by the FDA to grant permission for a specific patient to gain access to an experimental treatment. It is only for serious or life-threatening diseases or conditions for an investigational medical product for which there are no other comparable or satisfactory therapies available.  These therapies have not been formally approved for use by the FDA, but are usually in the investigative stage through other trials.  As with any therapy not formally approved there can be serious side effects, even fatal, and the effectiveness of the therapy isn’t known. 

Often the path to compassionate approval can be lengthy and difficult.  In order to gain approval, the patient must accomplish the following:

  • Approval from a Licensed Physician – In any compassionate use case, other than the initial request of the patient, the physician is the most integral to this process. He or she must have explored other treatment options and work with industry, the FDA and an Institutional Review Board (IRB) to gain approval for compassionate use of the therapy.  This is done in writing and may require updates and revisions.  Additionally, the physician must then oversee the administration of the therapy, general care and reporting of responses.
  • Approval of Industry – In any compassionate use case, the company producing the therapy must also approve of its use in these cases. Additionally, they also may be required to participate in the reporting process.
  • Approval of an IRB – The IRB’s role is to protect the rights of patients participating in any study. This is accomplished with an approval of the plan of administration of the therapy, the consents and communication with the patient to ensure that they understand the inherent issues of the treatment path.
  • Approval of the FDA – Lastly, the FDA must also review the request and determine if compassionate access is allowed.

Expanded Access of DIPG / DMG Treatments

The term Expanded Access is often used interchangeably with Compassionate Use, but often is used to refer to multi-patient programs of Compassionate Use. Although many of the approval thresholds still must be upheld, many formal Expanded Access programs effectively recognize a group of patients with the same diagnoses and set certain criteria for those that will be allowed to participate – much like a clinical trial.  In these cases, while the data still needs to be captured for patient safety, it may not be used for ultimate therapy approval with the FDA.  Typically Expanded Access programs are setup where clinical trials are limited, the type of disease is life-threatening and where there may be some foundational and industry support to bear the costs of both the therapy and also the reporting functions.  Expanded Access programs may also be used in cases where drug usage may be approved for one class of patients but not another – often dealing with access to certain age groups such as children when an adult version has approval.

Off-Trial Usage of DIPG / DMG Treatments

One particular option that isn’t often explored is Off-Trial Usage of a therapy. Here the compound may already have completed a phase 1 or phase 2 trial but the patient may not qualify for an existing trial due to progression, use of another drug or even certain functional limitations.  Sometimes it can also be used when a trial temporarily halts recruitment when it moves between phases.  In these cases, the treating physician may seek approval for an off-trial usage of the compound.  In this case, the approval may be slightly easier than compassionate use because the therapy may already be approved for limited use.  Once again, data may not be collected for drug approval, but will be reviewed for patient safety.  It is important that patients discuss this option with their doctor because often it may be an easier, but overlooked, path to treatment.

Provisional Use of DIPG / DMG Treatments

While not a current treatment pathway, Provisional Use is a proposed option that is the subject of the Promising Pathway Act. Here, advocates seek to recognize a new status with the FDA taking Compassionate Access to a provisional approval for 2 years or less, thus allowing groups of patients to participate and gain access to new therapies that are reasonably believed to be safe.  These patients will then be monitored for safety and the data would be recorded in a third-party registry for future approval processes.  To learn more about this pathway, visit  To help with the approval of this act, please contact your legislators below:

Contact Your Legislators

It is important to note that each of the above pathways do not deal with the financial aspect of participation and often are not covered by normal health insurance.  Still, they seek to open up options for the patients and are of particular significance to those fighting DIPG or DMG.