Right to Try: Mission accomplished?

 

On May 30, 2018, President Trump signed into law the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017, guaranteeing patients with terminal illnesses the right to seek access to investigational drugs which have passed at least phase 1 testing. As he signed the bipartisan-backed bill into law, the president said he believes it will ultimately save “hundreds of thousands” of lives, scoring an apparent win-win-win for the president, for Congress, and for patients. A critical appraisal of the law – and of the supposition that patients will reap great benefit from it – requires that we ask two questions: Does the law degrade measures originally put in place to protect patients, and does it actually improve access to potentially life-saving drugs?

As a hematologist with about 2 decades of experience conducting clinical research involving patients with incurable cancer, I want as many patients as possible to have access to promising new therapies. Clinical trials, as the sole means of determining a candidate drug’s safety and efficacy, are conducted in a systematic fashion, with phase 1 trials focusing predominantly on safety. As any experienced researcher is aware, however, a phase 1 trial only provides a basic sense of a drug’s safety. It would be unimaginable (and unethical) to conduct subsequent phase 2 and 3 trials without including rigorous ongoing monitoring for adverse effects.

Some critics of the Right to Try law feel that it potentially weakens landmark legislation originally put into place to protect the public from fraudulent and/or dangerous drugs, by permitting access before efficacy and safety is really established. When considering trends in phase 1 trials in oncology, at least, this concern might be tempered. In an analysis of all phase 1 trials originally submitted for presentation at the annual meetings of the American Society of Clinical Oncology between 1991 and 2002 (involving more than 6,000 individual patients being treated with drugs that had not been approved by the Food and Drug Administration at the time of abstract presentation), the treatment-related death rate was only 0.54%.¹

A later study evaluating all nonpediatric phase 1 trials sponsored by the National Cancer Institute’s Cancer Therapy Evaluation Program between 2001 and 2012, which included more than 8,300 patients, found the therapy-related death rate to be similarly low – approximately 1%.²

It is distinctly possible that the same drugs used in the analyzed trials would have been more toxic to patients who, for one reason or another, would not have met enrollment criteria. It is impossible to precisely quantify the degree to which risk may be increased under the Right to Try law, but even if it were tripled or quadrupled, compared with these historical expectations, the absolute risk of treatment-related death remains low. It should be noted that the incidence of nonfatal grade 3-4 adverse events in the same analyses was 10%-20% so a similar proportional increase in these events would impact a larger number of patients. Overall, it is difficult to know the degree to which Right to Try impacts the safety of fragile patients with terminal illnesses.

The answer to the second question – Is access to life-saving drugs improved? – is much easier to answer: No.

One reason is that these patients already have the right to seek access to investigational drugs through the FDA’s Expanded Access Program. An overview of the Expanded Access Program reported that approximately 11,000 patients over a period of 10 years submitted requests for access to investigational drugs and that 99% of the requests were granted.³

Proponents of the Right to Try law argue that the new law somehow simplifies the request process, but it is difficult to understand exactly how. Further, in a position paper on the topic of Right to Try policy, Lisa Kearns and Alison Bateman-House, PhD, of New York University, wrote, “In the more than 2½ years since the first [individual state right to try] law was signed, there have been no documented cases of anyone receiving access, because of a right to try law, to an experimental product that would not have been available via the FDA’s Expanded Access Program.”⁴

Finally, and most importantly, neither the existing Expanded Access Program nor the newly enacted Right to Try law require that pharmaceutical companies actually provide the requested drugs. Industry leaders, in testimony before Congress, have cited patient safety, costs, drug supply, and negative impact on existing clinical trial accrual as reasons pharmaceutical companies commonly deny requests for access to investigational products.

The bottom line is that the Right to Try law really lacks teeth. Despite the favorable optics for the president and Congress, it is virtually certain that Right to Try will never save hundreds of thousands of lives, and the suggestion that it will is either disingenuous or uninformed. Hopefully, though, Congress’s passage of Right to Try is indicative of a more general interest in bipartisan cooperation to improve access to affordable, high-quality health care.
 

 

Dr. Zonder is a professor in the department of oncology at the Barbara Ann Karmanos Cancer Institute and Wayne State University in Detroit. He is the leader of the KCI Myeloma and Amyloidosis Team. He is also a member of the Hematology News Editorial Advisory Board. He reported having no relevant financial disclosures.

References

1. Roberts TG Jr. et al. JAMA. 2004 Nov 3;292(17):2130-40.

2. Fukada YK et al. J Clin Oncol. 2014 May 20. doi: 10.1200/jco.2014.32.15_suppl.2552.

3. Jarow JP et al. Ther Innov Regul Sci. 2017 Mar 1;51(2):177-9.

4. Kearns L et al. Ther Innov Regul Sci. 2017 Mar 1;51(2):170-6.
 

 

On May 30, 2018, President Trump signed into law the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017, guaranteeing patients with terminal illnesses the right to seek access to investigational drugs which have passed at least phase 1 testing. As he signed the bipartisan-backed bill into law, the president said he believes it will ultimately save “hundreds of thousands” of lives, scoring an apparent win-win-win for the president, for Congress, and for patients. A critical appraisal of the law – and of the supposition that patients will reap great benefit from it – requires that we ask two questions: Does the law degrade measures originally put in place to protect patients, and does it actually improve access to potentially life-saving drugs?

As a hematologist with about 2 decades of experience conducting clinical research involving patients with incurable cancer, I want as many patients as possible to have access to promising new therapies. Clinical trials, as the sole means of determining a candidate drug’s safety and efficacy, are conducted in a systematic fashion, with phase 1 trials focusing predominantly on safety. As any experienced researcher is aware, however, a phase 1 trial only provides a basic sense of a drug’s safety. It would be unimaginable (and unethical) to conduct subsequent phase 2 and 3 trials without including rigorous ongoing monitoring for adverse effects.

Some critics of the Right to Try law feel that it potentially weakens landmark legislation originally put into place to protect the public from fraudulent and/or dangerous drugs, by permitting access before efficacy and safety is really established. When considering trends in phase 1 trials in oncology, at least, this concern might be tempered. In an analysis of all phase 1 trials originally submitted for presentation at the annual meetings of the American Society of Clinical Oncology between 1991 and 2002 (involving more than 6,000 individual patients being treated with drugs that had not been approved by the Food and Drug Administration at the time of abstract presentation), the treatment-related death rate was only 0.54%.¹

A later study evaluating all nonpediatric phase 1 trials sponsored by the National Cancer Institute’s Cancer Therapy Evaluation Program between 2001 and 2012, which included more than 8,300 patients, found the therapy-related death rate to be similarly low – approximately 1%.²

It is distinctly possible that the same drugs used in the analyzed trials would have been more toxic to patients who, for one reason or another, would not have met enrollment criteria. It is impossible to precisely quantify the degree to which risk may be increased under the Right to Try law, but even if it were tripled or quadrupled, compared with these historical expectations, the absolute risk of treatment-related death remains low. It should be noted that the incidence of nonfatal grade 3-4 adverse events in the same analyses was 10%-20% so a similar proportional increase in these events would impact a larger number of patients. Overall, it is difficult to know the degree to which Right to Try impacts the safety of fragile patients with terminal illnesses.

The answer to the second question – Is access to life-saving drugs improved? – is much easier to answer: No.

One reason is that these patients already have the right to seek access to investigational drugs through the FDA’s Expanded Access Program. An overview of the Expanded Access Program reported that approximately 11,000 patients over a period of 10 years submitted requests for access to investigational drugs and that 99% of the requests were granted.³

Proponents of the Right to Try law argue that the new law somehow simplifies the request process, but it is difficult to understand exactly how. Further, in a position paper on the topic of Right to Try policy, Lisa Kearns and Alison Bateman-House, PhD, of New York University, wrote, “In the more than 2½ years since the first [individual state right to try] law was signed, there have been no documented cases of anyone receiving access, because of a right to try law, to an experimental product that would not have been available via the FDA’s Expanded Access Program.”⁴

Finally, and most importantly, neither the existing Expanded Access Program nor the newly enacted Right to Try law require that pharmaceutical companies actually provide the requested drugs. Industry leaders, in testimony before Congress, have cited patient safety, costs, drug supply, and negative impact on existing clinical trial accrual as reasons pharmaceutical companies commonly deny requests for access to investigational products.

The bottom line is that the Right to Try law really lacks teeth. Despite the favorable optics for the president and Congress, it is virtually certain that Right to Try will never save hundreds of thousands of lives, and the suggestion that it will is either disingenuous or uninformed. Hopefully, though, Congress’s passage of Right to Try is indicative of a more general interest in bipartisan cooperation to improve access to affordable, high-quality health care.
 

 

Dr. Zonder is a professor in the department of oncology at the Barbara Ann Karmanos Cancer Institute and Wayne State University in Detroit. He is the leader of the KCI Myeloma and Amyloidosis Team. He is also a member of the Hematology News Editorial Advisory Board. He reported having no relevant financial disclosures.

References

1. Roberts TG Jr. et al. JAMA. 2004 Nov 3;292(17):2130-40.

2. Fukada YK et al. J Clin Oncol. 2014 May 20. doi: 10.1200/jco.2014.32.15_suppl.2552.

3. Jarow JP et al. Ther Innov Regul Sci. 2017 Mar 1;51(2):177-9.

4. Kearns L et al. Ther Innov Regul Sci. 2017 Mar 1;51(2):170-6.
 

 

On May 30, 2018, President Trump signed into law the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017, guaranteeing patients with terminal illnesses the right to seek access to investigational drugs which have passed at least phase 1 testing. As he signed the bipartisan-backed bill into law, the president said he believes it will ultimately save “hundreds of thousands” of lives, scoring an apparent win-win-win for the president, for Congress, and for patients. A critical appraisal of the law – and of the supposition that patients will reap great benefit from it – requires that we ask two questions: Does the law degrade measures originally put in place to protect patients, and does it actually improve access to potentially life-saving drugs?

As a hematologist with about 2 decades of experience conducting clinical research involving patients with incurable cancer, I want as many patients as possible to have access to promising new therapies. Clinical trials, as the sole means of determining a candidate drug’s safety and efficacy, are conducted in a systematic fashion, with phase 1 trials focusing predominantly on safety. As any experienced researcher is aware, however, a phase 1 trial only provides a basic sense of a drug’s safety. It would be unimaginable (and unethical) to conduct subsequent phase 2 and 3 trials without including rigorous ongoing monitoring for adverse effects.

Some critics of the Right to Try law feel that it potentially weakens landmark legislation originally put into place to protect the public from fraudulent and/or dangerous drugs, by permitting access before efficacy and safety is really established. When considering trends in phase 1 trials in oncology, at least, this concern might be tempered. In an analysis of all phase 1 trials originally submitted for presentation at the annual meetings of the American Society of Clinical Oncology between 1991 and 2002 (involving more than 6,000 individual patients being treated with drugs that had not been approved by the Food and Drug Administration at the time of abstract presentation), the treatment-related death rate was only 0.54%.¹

A later study evaluating all nonpediatric phase 1 trials sponsored by the National Cancer Institute’s Cancer Therapy Evaluation Program between 2001 and 2012, which included more than 8,300 patients, found the therapy-related death rate to be similarly low – approximately 1%.²

It is distinctly possible that the same drugs used in the analyzed trials would have been more toxic to patients who, for one reason or another, would not have met enrollment criteria. It is impossible to precisely quantify the degree to which risk may be increased under the Right to Try law, but even if it were tripled or quadrupled, compared with these historical expectations, the absolute risk of treatment-related death remains low. It should be noted that the incidence of nonfatal grade 3-4 adverse events in the same analyses was 10%-20% so a similar proportional increase in these events would impact a larger number of patients. Overall, it is difficult to know the degree to which Right to Try impacts the safety of fragile patients with terminal illnesses.

The answer to the second question – Is access to life-saving drugs improved? – is much easier to answer: No.

One reason is that these patients already have the right to seek access to investigational drugs through the FDA’s Expanded Access Program. An overview of the Expanded Access Program reported that approximately 11,000 patients over a period of 10 years submitted requests for access to investigational drugs and that 99% of the requests were granted.³

Proponents of the Right to Try law argue that the new law somehow simplifies the request process, but it is difficult to understand exactly how. Further, in a position paper on the topic of Right to Try policy, Lisa Kearns and Alison Bateman-House, PhD, of New York University, wrote, “In the more than 2½ years since the first [individual state right to try] law was signed, there have been no documented cases of anyone receiving access, because of a right to try law, to an experimental product that would not have been available via the FDA’s Expanded Access Program.”⁴

Finally, and most importantly, neither the existing Expanded Access Program nor the newly enacted Right to Try law require that pharmaceutical companies actually provide the requested drugs. Industry leaders, in testimony before Congress, have cited patient safety, costs, drug supply, and negative impact on existing clinical trial accrual as reasons pharmaceutical companies commonly deny requests for access to investigational products.

The bottom line is that the Right to Try law really lacks teeth. Despite the favorable optics for the president and Congress, it is virtually certain that Right to Try will never save hundreds of thousands of lives, and the suggestion that it will is either disingenuous or uninformed. Hopefully, though, Congress’s passage of Right to Try is indicative of a more general interest in bipartisan cooperation to improve access to affordable, high-quality health care.
 

 

Dr. Zonder is a professor in the department of oncology at the Barbara Ann Karmanos Cancer Institute and Wayne State University in Detroit. He is the leader of the KCI Myeloma and Amyloidosis Team. He is also a member of the Hematology News Editorial Advisory Board. He reported having no relevant financial disclosures.

References

1. Roberts TG Jr. et al. JAMA. 2004 Nov 3;292(17):2130-40.

2. Fukada YK et al. J Clin Oncol. 2014 May 20. doi: 10.1200/jco.2014.32.15_suppl.2552.

3. Jarow JP et al. Ther Innov Regul Sci. 2017 Mar 1;51(2):177-9.

4. Kearns L et al. Ther Innov Regul Sci. 2017 Mar 1;51(2):170-6.