FDA moving to expand access to experimental drugs

The FDA is taking steps to expand patients’ access to drugs that have not yet been approved for marketing, encouraging manufacturers to exclude fewer people from clinical trials and to publicize their policies about accessing drugs outside of clinical trials, according to a report from Government Accountability Office (GAO Report, GAO-19-630, September 9, 2019).

Clinical trials

Clinical trials often exclude patients by geography, age, or medical condition, and many stakeholders believe that the eligibility criteria are too narrow and exclude patients who are likely to be treated once a drug is approved, according to the GAO. Two recent laws have encouraged expanded access to pre-approved, or “investigational” drugs, the Federal Right to Try Act of 2018, which allows terminally ill patients and their doctors to request access to drugs without an FDA review process, and the FDA Reauthorization Act of 2017, which required the FDA to discuss and report on clinical trial inclusion and exclusion, and requires the GAO to report FDA’s actions to expand access to investigational drugs.

FDA efforts

The FDA has made efforts to make sure that historically excluded classes of people, like children, pregnant women, or patients with liver disease, can gain access to “investigational” drugs that have not been approved for marketing. The agency has met with stakeholders, reported on its meetings, and issued guidance on cancer drugs and on clinical trials more generally.

FDA issued four new draft guidance documents and one finalized guidance document in March 2019, aimed at expanding eligibility for cancer drug trials. Collectively, the guidance recommends that manufacturers attempt to include certain patient populations that have typically been excluded from participation, including children and adolescents; patients with HIV, hepatitis B or hepatitis C virus; patients with brain cancer; and patients with kidney, heart, or liver diseases. Rather than excluding these patients outright, FDA’s new guidance recommends ways to safely include them in trials, such as allowing testing on HIV-positive patients if they have not had an AIDS-defining infection within the past 12 months.

The FDA has more recently issued draft guidance that goes beyond cancer trials, recommending in June that manufacturers examine whether exclusion criteria are necessary to ensure safety or to achieve the study’s objectives, and avoid any unnecessary restrictions to a study’s population.

Despite the FDA’s efforts, drug manufacturers have not generally moved to expand eligibility for clinical trials. Only two out of ten surveyed by the GAO indicated that they had broadened their clinical trial eligibility criteria or intended to do so, while other drug manufacturers said that they had tried other ways to expand access to trials, such as reimbursing travel and hotel costs, or taking advantage of decentralized trials that took place in retail health clinics and patients’ homes, according to the report.

Beyond clinical trials, patients can also request access to investigative drugs through the FDA’s expanded access program or the federal Right to Try Act, and the FDA is taking steps to raise awareness about those programs. While the FDA has tried to use both programs to increase access to investigative drugs, it can only go so far, since neither program compels drug makers to provide access outside of a clinical trial.

The GAO received mixed feedback on the FDA’s program. Some physician and patient advocacy groups criticized it as too complex and burdensome, while others pointed out that the FDA approves most requests—99 percent in 2017—and that manufacturer’s approval is a bigger factor in preventing patient access.

The FDA has tried to simplify and improve the expanded access process, simplifying forms and enlisting an outside partner to help physicians and patients find drug manufacturers’ expanded access policies, according to the report. The FDA has also started a pilot program to assist oncologists with requests for investigative drugs, and created a streamlined process for institutional review board approval, both of which have been well-received by stakeholders.

The newer Right to Try Act also received mixed reviews in the GAO’s study, with some physicians and medical ethicists questioning whether the program, which eliminates FDA review, could compromise patient safety without solving the more common obstacle to improving access, which is manufacturers’ cooperation.

Drug manufacturers remain skittish about the FDA’s handling of adverse events that occur under the FDA’s expanded access program, despite recent guidance saying that such events have not prevented FDA from approving any drug. Two out of ten drug manufacturers said that recent the FDA guidance did not quell their concerns, and four in ten said that manufacturers’ concerns about the issue “may never be fully resolved.” FDA officials, for their part, told the GAO that data from the expanded access program has been commonly used to support drug approvals, and only very rarely has led to a clinical hold.

The GAO also tracked drug makers’ efforts to communicate with patients about access to investigative drugs, finding that 23 of 29 manufacturers surveyed communicated their position to potential patients. Nineteen said they would consider requests for investigational drugs outside of clinical trials, while four said they would not consider requests, with two citing safety concerns. Most of the manufacturers willing to accept requests included an estimated time frame for responses, and five mentioned specific drugs for which they would consider requests.

Medicaid third-party liability changes a challenge for states

The U.S. Government Accountability Office (GAO) conducted a study to see the progress states have made in implementing the changes in third-party liability requirements since the Bipartisan Budget Act of 2018 was passed. The GAO found that the states are unclear on how to collect the required information, update their data systems, and implement the new policies. Adding to the difficulties in understanding and implementing the changes, CMS has issued inconsistent guidance and offers only outdated policy manuals that offer no assistance in implementing the changes (GAO Report, GAO-19-601, August 9, 2019).

Bipartisan Budget Act of 2018

Federal law requires states ensure that Medicaid is the payer of last resort by taking steps to identify Medicaid beneficiaries’ other potential sources of health coverage and their legal liability. The Bipartisan Budget Act of 2018 modified the required processes states must follow when paying claims with probable third-party liability for three types of services. Under the amended statute, states must apply cost avoidance procedures to claims for prenatal care services and pregnancy-related services when it is apparent that a third party is or may be liable at the time the claim is filed. Additionally, states are no longer required to pay claims for pediatric preventative services immediately and may instead require the provider to submit the claim to the third party and wait 90 days (wait-and-see period) for payment before seeking Medicaid payment. Finally, states must make payment for a child support enforcement (CSE) beneficiary’s claim if the third party has not paid the provider’s claim within a 100-day wait-and-see period.

State concerns

According to state officials, several changes to administrative tasks and the Medicaid Management Information System (MMIS) needed to be undertaken to implement the new third-party liability changes and some required research and discussion about the best methods to make these changes. Officials noted that they would need to identify the correct codes in their data systems, establish some sort of indicators in their system to identify which claims were for CSE beneficiaries or had been billed to a third party and when. Some of this additional information would require a data sharing agreement with the state entity maintaining the CSE information while other information would require providers to track down insurance information from a non-custodial parent. Some officials expressed concern that the system changes may require new hardware and system modifications and may make it difficult or impossible to implement the changes, while others discussed waiting for the new MMIS that they were already working to roll out in the future. There were also concerns that the technology changes and the increased administrative work may make the changes not cost-effective to implement.

Stakeholder concerns

Stakeholders were concerned that obtaining accurate information on third-party liability sources for Medicaid beneficiaries and resubmitting claims that result from incorrect or outdated information can be resource intensive and time consuming. Medicaid beneficiaries may be unaware or may not disclose other insurance policies, especially when there are multiple policies by custodial and non-custodial parents or transitions in insurance following birth. Some stakeholders were concerned that rural-based providers may not have the resources to deal with the increased administrative work and delays in payment for services that could result from the payment changes. This may lead some providers to be less willing to serve Medicaid beneficiaries, which would potentially reduce access to care or delay time-sensitive services for children and pregnant women. Some providers may also seek to identify sources of third-party liability before providing services to beneficiaries, which would also delay access to care.

Recommendations

Many states expressed the need for further guidance from CMS on how to implement some of these changes, however, the GAO noted that CMS has issued guidance that is inconsistent with the federal laws and some CMS guidance documents are out of date and not a reliable source of information for states to use in implementing the new requirements. Therefore, the GAO recommended that CMS ensure the agency’s Medicaid third-party liability guidance is consistent with federal law.

The GAO found that CMS has not taken steps to determine the extent to which state Medicaid agencies are meeting the new requirements and indicated that they expect states to comply and will not verify unless the agency is made aware of non-compliance. The GAO recommended that CMS determine the extent to which state programs are meeting federal third-party liability requirements and take actions to ensure compliance where appropriate.

Rural hospitals hit hard by reductions in Medicare disbursements, declining population

Approximately 3 percent of all rural hospitals closed in the period between 2013 and 2017, which can affect rural residents’ access to health care services. The U.S. Government Accountability Office (GAO) did a study to determine how HHS supports and monitors rural hospitals’ financial viability and rural residents’ access to hospital services. The study also details the number and characteristics of rural hospitals that have closed as well as what is known about the factors that contributed to those closures. According to the GAO report, Medicare Dependent Hospitals and for-profit hospitals were some of the hardest hit by reductions in Medicare disbursements, while hospitals in Medicaid expansion states and states with higher enrollment under the Patient Protection and Affordable Care Act (ACA) (P.L. 111-148) were the least affected (GAO Report, GAO-18-634, September 30, 2018).

Rural hospitals

In 2017, 2,250 general acute care hospitals in the United States met the definition of rural. Rural hospitals represented approximately 48 percent of hospitals nationwide and 16 percent of inpatient beds. Rural hospitals spread across 84 percent of the United States land area that is classified as rural and served 18 percent of the United State population that lived in those areas. Rural areas tend to have a higher percentage of elderly residents than urban areas, a higher percentage of residents with limitations in activities caused by chronic conditions, and a lower median household income. Rural areas also face a decreasing population and slow employment growth.

Payment policies and programs

HHS provides key financial support to rural hospitals to provide rural residents access to hospital services through a number of payment policies and programs. CMS administers five rural hospital payment designations, in which rural or isolated hospitals that meet specified eligibility criteria receive higher reimbursement for hospital services than they otherwise would have received under Medicare’s standard payment methodology. The Federal Office of Rural Health Policy (FORHP) administers multiple grant programs, cooperative agreements, and contracts that provide funding and technical assistance to rural hospitals. CMS’s Center for Medicare and Medicaid Innovation tests new ways to deliver and pay for healthcare. There are also the broader HHS payment policies and programs such as Medicare and Medicaid base payments, Medicare and Medicaid uncompensated care payments, the state innovation models initiative, as well as other targeted HHS payment policy and programs.

Rural hospital closures

An analysis of data shows that from 2013 through 2017, 64 rural hospitals closed. This is more than twice the number of rural hospitals that closed during the prior 5-year period and accounts for more than the share of urban hospitals that closed and more than the number of rural hospitals that opened. Rural hospitals in the South represented 38 percent of the rural hospitals in 2013 but accounted for 77 percent of the rural hospital closures from 2013 through 2017. Medicare dependent hospitals represented 9 percent of the rural hospitals in 2013 but accounted for 25 percent of the rural hospital closures.

For-profit hospitals are twice as likely to experience financial distress relative to government-owned and non-profit hospitals and represented 11 percent of rural hospitals in 2013 but accounted for 36 percent of closures. Bed size also seems to be a factor as rural hospitals with between 26 and 49 inpatient beds represented 11 percent of the rural hospitals in 2013 but accounted for 23 percent of the closures. While critical access hospitals (CAHs), which have 25 acute inpatient beds or less and make up a majority of the rural hospitals, were less likely than other rural hospitals to close. This may be due, in part, to the CAH payment designation.

Contributing factors

Data shows that rural hospital closures were generally preceded and caused by financial distress. This is partially due to a decrease in patients seeking inpatient care at rural hospitals. There are an increasing number of federally qualified health centers or newer hospital systems outside of the area that create increased competition for rural hospitals. Technological advances have also allowed for more services to be provided in outpatient settings. There is also data showing that the years 2010 through 2016 marked the first recorded period of rural population decline.

Rural hospitals are sensitive to changes in Medicare payments because, on average, Medicare accounted for approximately 46 percent of their gross patient revenues in 2016. Reductions in nearly all Medicare reimbursements and reductions in Medicare bad debt payments have contributed to negative margins for rural hospitals.

Medicaid expansion

According to stakeholders that were interviewed and literature that was reviewed, the strongest factor that likely strengthened the financial viability of rural hospitals was the increased Medicaid eligibility and enrollment under the ACA. A 2018 study showed that Medicaid expansion was associated with improved hospital financial performance and a substantially lower likelihood of closure, especially in rural markets. Drops in uninsured rates in 2008 through 2009 and 2014 through 2015 corresponded with states’ decisions to expand Medicaid, with small towns and rural areas seeing the largest increase in Medicaid coverage and decline in uninsured. Data shows that from 2013 through 2017, rural hospitals in states that had expanded Medicaid as of April 2018 were less likely to close compared with rural hospitals in states that had not expanded Medicaid.

Four VA facilities weak on controlled substance diversion protections

In recent years, diversion of controlled substances has occurred at several Veterans Affairs (VA) medical facilities. In fact, in a 2009 and 2014 report, the VA Office of the Inspector General (OIG) identified a number of weaknesses in VA medical facilities’ implementation of controlled substance inspection programs. For example, the VA OIG found that some VA medical facilities had not conducted the required monthly inspections, and when facilities did conduct the monthly inspections, the inspections were sometimes incomplete because they did not follow all of the required Veterans Health Administration (VHA) procedures.

GAO review

As a result of these deficiencies, Congress requested that the Government Accountability Office (GAO) report on VHA’s processes to reduce the risk of diversion of controlled substances at its medical facilities and VHA’s oversight of these processes. The report examined: (1) the extent to which selected VA medical facilities have implemented controlled substance inspection programs as required by VHA policies, and (2) VHA’s oversight of these programs at selected VA medical facilities.

Implementation of inspections

The GAO found weaknesses in the way four VA medical facilities were implementing their controlled substance inspection programs. Two of the four facilities did not conduct monthly inspections of controlled substances as required by the VHA. Between January 2015 and February 2016, one facility missed 43 percent of monthly inspections in critical patient care areas and the pharmacy. Further, inspections that three of the four facilities performed did not include or follow three or more of the nine VHA requirements. At two of the three facilities, inspectors did not properly verify that controlled substances had been transferred from VA pharmacies to patient care areas; nor did inspectors ensure that all controlled substances on hold for destruction were properly documented.

Contributing factors

GAO discovered that several factors contributed to the failure to adhere to VHA policy. First, the two facilities that missed inspections lacked an additional control procedure (such as the use of an alternate controlled substance coordinator) to help prevent missed inspections when inspectors could not conduct them due to professional or other personal responsibilities. Second, three of the four facilities did not ensure their written procedures included the nine VHA program requirements. Third, while the VHA relies on coordinators at the facilities to ensure that the inspections are completed appropriately, the GAO found that VHA’s training course for the coordinators does not focus on its required inspection procedures.

Inconsistent oversight

The GAO also found inconsistent oversight at the selected facilities of their controlled substance inspection programs by facility directors and the Veterans Integrated Service Networks to which the facilities report. Directors at two of the four selected VA medical facilities had not implemented corrective actions to address missed inspections identified in the monthly inspection reports. In addition, two of the four selected networks did not review their facilities’ quarterly trend reports, as required by VHA. One network that had reviewed the trend reports failed to follow up with a facility to ensure it had submitted missed trend reports. The GAO concluded that without effective oversight of the inspection programs by directors and networks, VHA lacks reasonable assurance that its programs are being implemented as required to prevent and identify diversion of controlled substances.

Recommendations

The GAO recommended that the Secretary of the VA direct the Under Secretary for Health to:

  • ensure that VA medical facilities have established an additional control procedure, such as an alternate controlled substance coordinator or additional inspectors, to help coordinators meet their responsibilities and prevent missed inspections;
  • ensure that VA medical facilities have established a process where coordinators, in conjunction with pharmacy officials, periodically compare facility inspection procedures to VHA’s policy requirements and modify facility inspection procedures as appropriate;
  • improve the training of VA medical facility controlled substance coordinators by ensuring the training includes the inspection procedures that VHA requires;
  • ensure that medical facility directors have designed and implemented a process to address nonadherence with program requirements, including documenting the nonadherence and the corrective actions taken to remediate nonadherence or the actions that demonstrate why no remediation is necessary; and
  • ensure that networks review their facilities’ quarterly trend reports and ensure facilities take corrective actions when nonadherence is identified.

The VA concurred with the GAO’s recommendations.