National Right to Try legislation was passed by Congress last week in an effort to make investigational drugs more readily available to patients who have no other treatment options available to them. However, many believe this legislation will do little to help patients and have argued that regulators should focus less on passing new laws and focus more on the current FDA Expanded Access framework as well as on improving access to clinical trials.
Clinical trials are considered the safest and most effective way of making investigational drugs available to patients. However, trials are often restrictive due to stringent eligibility criteria which exclude patients based on factors including age, gender, medical history, use of concomitant medication, etc. These criteria are put in place to create the ‘perfect’ population of trial patients, i.e. the group of patients expected to respond most effectively to the new drug. However, as a result of this, clinical trials can exclude a large percentage of the patient population who are in desperate need of treatment.
In 2016, ASCO, Friends of Cancer Research, and the FDA began conducting a study examining five specific eligibility criteria to determine whether modifications could be made to any or all of them in order to make oncology clinical trials more inclusive. The five criteria examined were minimum age, HIV infection, brain metastases, organ dysfunction, and prior and concurrent malignancies. Working groups then developed consensus recommendations based on the evidence generated, consultation with the research community, and consideration of the patient population.
Below is a summary of the recommendations for each criterion.
Minimum Age for Enrollment
Pediatric patients are often excluded from trials for new cancer treatments. As a result, patients under the age of 18 can be forced to wait until a drug has been tested and approved for use in the adult population before accessing it. Based on the study, the following two recommendations have been presented:
- For later-phase clinical trials, pediatric patients should be considered for cancers that affect both adults and children. As a minimum, children over the age of 12 should routinely be able to access these trials, as their metabolism is similar enough to an adult’s metabolism. Children younger than the age of 12 should be considered if they are included in the overall patient population impacted by the disease.
- For early stage clinical trials, pediatric patients should be included when there is scientific evidence to suggest that these patients will benefit and there is adequate information available to reduce the risk to these patients.
Despite the fact that cancer has become the leading cause of death in HIV patients, oncology clinical trials usually exclude these patients. These patients are often considered too ‘risky’ to include, as they could have a serious adverse event (death) while taking the drug that is related to the HIV and not the medication. However, HIV patients now have greatly improved treatment options available to them, resulting in near to normal life expectancy for the majority of the patient population. Based on the study, the following recommendations have been presented:
- HIV patients shown to be at low risk of experiencing an AIDS-related adverse event should be included in trials for all study phases, especially for those cancers commonly associated with HIV.
- HIV patients enrolled in a clinical trial should be allowed to continue receiving standard antiretroviral therapy.
- When a HIV patient is enrolled in a clinical trial, he/she should be treated according to the exact same standards as non-HIV patients.
Similarly to HIV patients, patients with brain metastases are often considered too ‘risky’ to include in oncology clinical trials and are prevented from enrolling. This continues to occur despite the fact that many of these patients experience stable brain metastases and are, therefore, less likely to experience an adverse event related to the condition. Based on the study, the following recommendations have been presented:
- As long as there are no obvious safety concerns, patients with brain metastases should be considered for cancer clinical trials in all phases, if they have stable brain metastases four weeks before entering the study.
- Patients with brain metastases should be included in early stage clinical trials for drugs being developed to treat patient populations in which brain metastases are common.
Cancer patients who suffer from organ dysfunction, such as renal disease, cardiac disease, or liver dysfunction, are commonly excluded from clinical trials. However, due to our aging population, it is becoming increasingly common for cancer patients to suffer from these kinds of additional conditions. Excluding these patients from the trials, therefore, results in a very narrow understanding of how the drug will work in the larger patient population once it is approved. Based on the study, the following recommendations have been presented:
- Patients suffering from some kind of organ dysfunction should not be excluded from a trial if the investigational drug is not linked to the organ dysfunction.
- When the investigational drug is linked to the organ dysfunction, patients should not be excluded from a trial, as long as the link does not pose any health or safety concern.
- Where organ function is not adequately measured with available tests, as with liver dysfunction, enrollment should include standard clinical assessment
Prior or Concurrent Malignancies
Patients with a prior history of cancer or with two concurrent cancer diagnoses are more likely to be excluded from clinical trials than those patients with no prior or concurrent malignancies. Based on the study, the following recommendation has been presented:
- Patients with a prior or concurrent malignancy should be included in a clinical trial if the natural history or concomitant medication will not interfere with the safety or efficacy evaluation of the investigational drug.
According to ASCO President, Bruce E. Johnson, the recommendations above provide a roadmap for how to safely and effectively include a greater number of patients in clinical trials. These sentiments have been echoed by Dr. Jeff Allen, President & CEO of Friends of Cancer Research, who claims that broadening the eligibility criteria will improve access and ensure that trial results are more reflective of the greater patient population.
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