‘Right to Try’: Expanding access for terminally ill patients

As the Right to Try Act of 2017 moves from Senate approval to the House floor, the FDA continues to facilitate expanded access to investigational drugs for terminally ill patients with streamlined case review and clarified instructions for adverse event reports.

“The Right to Try Act is an alternative pathway. I don't think it's necessarily there to replace the FDA Expanded Access program currently in place,” Neha K. Patel, PharmD, associate at Arnold & Porter Kaye Scholer LLP, told Healio.com/Hepatology. “There are pros and cons to having an individual patient contact a manufacturer.”

According to Patel, while neither option guarantees access from a manufacturer, there may be added risk with the Right to Try process as patients would not have the expertise of the FDA or a physician’s submitted request to validate their case. “There is more vulnerability on the Right to Try Act in my opinion, but any increased access to experimental products — especially for this terminally ill population — is good. This is a good effort. It will be interesting to see how it plays out.

Streamlined process

“FDA has a long history of supporting patient access to investigational new treatments. This includes working with drug and device companies through the clinical trial process that may lead to FDA approval of the treatment,” Scott Gottlieb, MD, commissioner of the FDA, wrote in the FDA’s blog. “We’re committed to helping patients and physicians fully understand the expanded access process.”

Scott Gottlieb, MD
Scott Gottlieb

One of the FDA’s early steps to streamline expanded access was to slim down the application process. According to Gottlieb, the application now takes approximately 45 minutes to complete. Additionally, the FDA released guides that explain what expanded access is, when and how to submit a request, the type of information necessary to apply, and when patients may be charged for investigational drugs.

A rule by the HHS and administered by the NIH and FDA requires manufacturers sponsoring clinical trials to submit information to ClincialTrials.gov that indicates whether expanded access is available for an investigational drug and, if so, any pertinent information physicians or patients would need to apply for access.

On Oct. 3, 2017, the FDA announced an additional improvement to streamline the application process: at the request of the physician, only one Investigational Review Board (IRB) member — the chair or another appropriate person — can approve treatment use. “I believe a simplified IRB process will facilitate access while still protecting patients,” Gottlieb said in a testimony before the Subcommittee on Health of the U.S. House of Representatives.

“The current FDA Expanded Access program includes IRB approval and the FDA has to they think the potential benefit of using the experimental drug in a patient outweighs the risks – then and only then can the expanded access use be approved,” Patel said. “The Right to Try legislation is different in that it does not require the FDA to have this so-called ‘middle man’ type of role.”

Adverse event reports

The FDA also updated its “Expanded Access to Investigational Drugs for Treatment Use: Questions and Answers” guide, specifically to clarify requirements for adverse event reports in expanded access cases.

“Patients receiving treatment through expanded access may have more advanced disease than clinical trial participants, have multiple diseases, and/or be receiving other drugs at the same time,” Gottlieb said in his testimony. “These factors make it more difficult to be certain about the cause of an adverse event.”

As with any investigational new drug application, clinical trial sponsors are responsible for submitting safety reports and annual reports in all cases of expanded access. In the case of expanded access, however, the updated guide states that sponsors must report an adverse event as a suspected adverse reaction only if there is evidence to suggest a causal relationship between the drug and event.

According to Gottlieb, the FDA is not aware of cases in which adverse event reports from expanded access have prevented FDA approval of a drug and that FDA reviewers understand the context in which the expanded access was used.

Right to Try Act

The Right to Try Act of 2017 was designed to provide physicians unrestricted access to experimental drugs, biological products and medical devices authorized by state law for patients diagnosed with a “terminal illness,” defined as a patient certified by a physician who has exhausted all other treatment options.

“There are a lot of considerations related to having this alternative pathway compared with the current structure of Expanded Access that the FDA has right now,” Patel said. “Similar to what the FDA has in place with Expanded Access, the Right to Try Act can't compel a manufacturer to provide expanded access.”

Patel voiced concern, however, regarding the potential lack of expert oversight in Right to Try compared with Expanded Access. While manufacturers will still evaluate whether or not to provide an experimental drug to a patient, it seems, according to Patel, that the Right to Try Act merely removes the FDA’s objective analysis from the procedure.

“That is not there in the Right to Try legislation. That just opens up the question of who, if at all, would be conducting that objective, expert, scientifically-based evaluation if Right to Try is approved? There should be some provision for that,” Patel said. “The FDA's role in this has been to protect the patient from these kind of misguided 'hail Mary' attempts that could cause more harm than benefit.”

The bill also was designed to protect manufacturers, distributors, prescribers, dispensers, possessors and users of expanded access investigational drugs from liability regarding the treatment. The outcome of expanded access similarly may not be used by a federal agency to adversely impact review or approval of the treatment.

Finally, the treatment must meet the following requirements: completed a phase 1 clinical trial; remain under investigation for approval by the FDA; and remain unapproved during expanded access of the drug.

“Supporting patients facing such difficult situations by helping to facilitate their access to investigational therapies is a high priority for the administration,” Gottlieb said in his testimony regarding the bill. “The administration looks forward to working with Congress to help patients and their families explore available treatment options in a responsible and ethical manner, including through right to try legislation.” – by Talitha Bennett

References:

Gottlieb S. Expanded Access: FDA Describes Efforts to Ease Application Process. https://blogs.fda.gov/fdavoice/index.php/2017/10/expanded-access-fda-describes-efforts-to-ease-application-process/ Updated October 3, 2017. Accessed October 9, 2017.

Gottlieb S. Examining Patient Access to Investigational Drugs. http://docs.house.gov/meetings/IF/IF14/20171003/106461/HHRG-115-IF14-Wstate-GottliebS-20171003.pdf Updated October 3, 2017. Accessed October 9, 2017.

U.S. Department of Health and Human Services. Expanded Access to Investigational Drugs

for Treatment Use — Questions and Answers. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM351261.pdf Updated October 2017. Accessed October 9, 2017.

As the Right to Try Act of 2017 moves from Senate approval to the House floor, the FDA continues to facilitate expanded access to investigational drugs for terminally ill patients with streamlined case review and clarified instructions for adverse event reports.

“The Right to Try Act is an alternative pathway. I don't think it's necessarily there to replace the FDA Expanded Access program currently in place,” Neha K. Patel, PharmD, associate at Arnold & Porter Kaye Scholer LLP, told Healio.com/Hepatology. “There are pros and cons to having an individual patient contact a manufacturer.”

According to Patel, while neither option guarantees access from a manufacturer, there may be added risk with the Right to Try process as patients would not have the expertise of the FDA or a physician’s submitted request to validate their case. “There is more vulnerability on the Right to Try Act in my opinion, but any increased access to experimental products — especially for this terminally ill population — is good. This is a good effort. It will be interesting to see how it plays out.

Streamlined process

“FDA has a long history of supporting patient access to investigational new treatments. This includes working with drug and device companies through the clinical trial process that may lead to FDA approval of the treatment,” Scott Gottlieb, MD, commissioner of the FDA, wrote in the FDA’s blog. “We’re committed to helping patients and physicians fully understand the expanded access process.”

Scott Gottlieb, MD
Scott Gottlieb

One of the FDA’s early steps to streamline expanded access was to slim down the application process. According to Gottlieb, the application now takes approximately 45 minutes to complete. Additionally, the FDA released guides that explain what expanded access is, when and how to submit a request, the type of information necessary to apply, and when patients may be charged for investigational drugs.

A rule by the HHS and administered by the NIH and FDA requires manufacturers sponsoring clinical trials to submit information to ClincialTrials.gov that indicates whether expanded access is available for an investigational drug and, if so, any pertinent information physicians or patients would need to apply for access.

On Oct. 3, 2017, the FDA announced an additional improvement to streamline the application process: at the request of the physician, only one Investigational Review Board (IRB) member — the chair or another appropriate person — can approve treatment use. “I believe a simplified IRB process will facilitate access while still protecting patients,” Gottlieb said in a testimony before the Subcommittee on Health of the U.S. House of Representatives.

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“The current FDA Expanded Access program includes IRB approval and the FDA has to they think the potential benefit of using the experimental drug in a patient outweighs the risks – then and only then can the expanded access use be approved,” Patel said. “The Right to Try legislation is different in that it does not require the FDA to have this so-called ‘middle man’ type of role.”

Adverse event reports

The FDA also updated its “Expanded Access to Investigational Drugs for Treatment Use: Questions and Answers” guide, specifically to clarify requirements for adverse event reports in expanded access cases.

“Patients receiving treatment through expanded access may have more advanced disease than clinical trial participants, have multiple diseases, and/or be receiving other drugs at the same time,” Gottlieb said in his testimony. “These factors make it more difficult to be certain about the cause of an adverse event.”

As with any investigational new drug application, clinical trial sponsors are responsible for submitting safety reports and annual reports in all cases of expanded access. In the case of expanded access, however, the updated guide states that sponsors must report an adverse event as a suspected adverse reaction only if there is evidence to suggest a causal relationship between the drug and event.

According to Gottlieb, the FDA is not aware of cases in which adverse event reports from expanded access have prevented FDA approval of a drug and that FDA reviewers understand the context in which the expanded access was used.

Right to Try Act

The Right to Try Act of 2017 was designed to provide physicians unrestricted access to experimental drugs, biological products and medical devices authorized by state law for patients diagnosed with a “terminal illness,” defined as a patient certified by a physician who has exhausted all other treatment options.

“There are a lot of considerations related to having this alternative pathway compared with the current structure of Expanded Access that the FDA has right now,” Patel said. “Similar to what the FDA has in place with Expanded Access, the Right to Try Act can't compel a manufacturer to provide expanded access.”

Patel voiced concern, however, regarding the potential lack of expert oversight in Right to Try compared with Expanded Access. While manufacturers will still evaluate whether or not to provide an experimental drug to a patient, it seems, according to Patel, that the Right to Try Act merely removes the FDA’s objective analysis from the procedure.

PAGE BREAK

“That is not there in the Right to Try legislation. That just opens up the question of who, if at all, would be conducting that objective, expert, scientifically-based evaluation if Right to Try is approved? There should be some provision for that,” Patel said. “The FDA's role in this has been to protect the patient from these kind of misguided 'hail Mary' attempts that could cause more harm than benefit.”

The bill also was designed to protect manufacturers, distributors, prescribers, dispensers, possessors and users of expanded access investigational drugs from liability regarding the treatment. The outcome of expanded access similarly may not be used by a federal agency to adversely impact review or approval of the treatment.

Finally, the treatment must meet the following requirements: completed a phase 1 clinical trial; remain under investigation for approval by the FDA; and remain unapproved during expanded access of the drug.

“Supporting patients facing such difficult situations by helping to facilitate their access to investigational therapies is a high priority for the administration,” Gottlieb said in his testimony regarding the bill. “The administration looks forward to working with Congress to help patients and their families explore available treatment options in a responsible and ethical manner, including through right to try legislation.” – by Talitha Bennett

References:

Gottlieb S. Expanded Access: FDA Describes Efforts to Ease Application Process. https://blogs.fda.gov/fdavoice/index.php/2017/10/expanded-access-fda-describes-efforts-to-ease-application-process/ Updated October 3, 2017. Accessed October 9, 2017.

Gottlieb S. Examining Patient Access to Investigational Drugs. http://docs.house.gov/meetings/IF/IF14/20171003/106461/HHRG-115-IF14-Wstate-GottliebS-20171003.pdf Updated October 3, 2017. Accessed October 9, 2017.

U.S. Department of Health and Human Services. Expanded Access to Investigational Drugs

for Treatment Use — Questions and Answers. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM351261.pdf Updated October 2017. Accessed October 9, 2017.

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