Clinical News Roundup: FDA Issues 3 Final Guidances For Expanded Access

By Ed Miseta, Chief Editor, Clinical Leader

The FDA has issued three final guidances for the pharma industry related to expanded access – the FDA process to facilitate the availability of investigational treatment options to patients with serious or immediately life-threatening diseases or conditions who lack therapeutic alternatives.

The first guidance, titled “Individual Patient Expanded Access Applications: Form FDA 3926,” describes a streamlined option for licensed physicians to request use of an investigational new drug to treat individual patients who have exhausted other treatment options, including for emergency use.  When Form FDA 3926 is substituted for the current Forms FDA 1571 and 1572, the agency estimates that each submission will take only 45 minutes, resulting in a significant burden reduction.

The second guidance is titled “Expanded Access to Investigational Drugs for Treatment Use – Questions and Answers” and responds to frequently asked questions about the implementation of FDA’s regulations on expanded access to investigational drugs. 

The third guidance, titled “Charging for Investigational Drugs Under an IND – Questions and Answers,” responds to frequently asked questions about the implementation of FDA’s regulation on charging for investigational drugs under an investigational new drug (IND) application in the context of clinical trials or expanded access for treatment use. 

According to the FDA, these steps are designed to simplify and provide clarity about expanded access. And, they will help healthcare professionals, patients, and industry to more easily navigate the expanded access process and enable patients who qualify to access potentially life-saving medications more readily. FDA has also developed patient and physician fact sheets to further inform stakeholders about expanded access and has revamped its website to make it more user-friendly. 

4 Tips On Writing An RBM Plan

Moe Alsumidaie, chief data scientist at Annex Clinical and contributor to Applied Clinical Trials, has produced an article detailing four tips on writing an RBM (risk-based monitoring) plan. “With recent changes in industry execution and increasing experiences with using RBM, many peers are inquiring about how to write an RBM plan,” he says. “Hence, we thought it would be beneficial to provide a brief methodology on developing a risk management process to create an RBM plan.”

First, Alsumidaie recommends completing a Risk Assessment Categorization Tool (RACT). Although evidence shows the RACT could introduce subjectivity, it can help get study teams to think about revealing and ranking study risks. The RACT is most effective when done during the protocol development phase and can mitigate study risks by enabling teams to redesign the protocol.

Identifying critical study risks is tip number two. These can occur from data collection through enrollment. Alsumidaie notes it is important to define and categorize risks in a way that regulatory authorities consider important. Critical risks involve data related to the study endpoints and patient safety. Data that is not considered critical should be put in the non-critical risk category.

Tip three is to transform critical risks into analytical measurements. Alsumidaie notes this is where key risk indicators (KRIs) come into play. The RBM Consortium defines a KRI as an objective measurement of a study-related parameter against a preset threshold providing a signal about the risk of a study process or any of its deliverables. KRIs will measure the achievement of an operational or performance target.

Tip four is to write the RBM plan. By the time you get to step four, most of the work has been done. That should make this the easiest step. This step involves structuring your RBM plan in a coherent way so any auditor not familiar with the study can grasp the rationale behind it.

“A comprehensive RBM plan is based on thorough risk-management preparation,” adds Alsumidaie. “Writing a good RBM plan not only enables you to focus resources on critical study areas, but also provides both auditors and regulators with a good impression of risk interpretation and monitoring proficiency. A well-designed study is the blueprint for good quality.”

It’s Time To Fix Clinical Trial Reimbursement

Writing for The Hill, Alan Balch, CEO of the National Patient Advocate Foundation, notes that Congress and the Obama administration are working to accelerate the pace of cures in the U.S. With that effort underway, this may also be a good time to take stock of the progress and challenges in bringing new treatments to cancer patients.

“On the plus side, progress against cancer is occurring at breakneck speed,” says Balch. “In 2015 alone, the FDA approved 14 novel cancer medicines, including 10 immunotherapies that free up the body’s immune system to recognize and destroy specific cancer cells. Additionally, scientific discoveries are changing cancer care from a one-size-fits-all approach to precision therapy where the genetic and molecular profile of the patient’s cancer determines the best treatment strategy.”

But problems still exist. Researchers continue to have difficulty recruiting patients for cancer clinical trials, where only two to five percent of adult eligible patients participate. One reason are the myths and misperceptions that exist regarding trials. Better education can help fix that problem, and a number of initiatives are underway to inform patients and raise the level of awareness of trials. But that is only part of the solution. Balch believes health plans need to cover the routine medical costs when patients are enrolled in clinical studies.

“These are not the cost of procedures, drugs, extra doctor visits, and expenses directly related to the study itself, which are usually covered by the trial sponsors,” says Balch. “What are at issue are the charges insurance normally covers, such as such as physician fees, hospital charges, and routine tests. While many insurers offer coverage for clinical trials, some health plans deny reimbursement due to liability concerns while others limit coverage to the extent that patients wanting to enroll in a trial cannot do so. In these situations, patients are left with the difficult choice of having to pay the out of pocket costs or forgoing the trial altogether.”

Although Section 2709 of the Affordable Care Act (ACA) mandated group health plans and insurance issuers cover regular medical costs when patients are in a clinical study, the original language lacked the specificity payers and providers needed. On April 20, 2016 the Departments of Labor, Health and Human Services, and the Treasury jointly issued a clarification document to answer persistent questions about ACA provisions, including what expenses are considered the “routine patient costs” associated with clinical trials. It also specifies what expenses are not covered.

“Now that insurers have detailed information on coverage requirements, it is time for those health plans that have yet to cover clinical trial costs to do so,” states Balch. “Patients need greater access to, and reimbursement for, breakthrough treatments available through clinical trials and the clarification document put to rest any lingering questions.”

Should Patients And Doctors Rethink The Value Of Phase 1 Trials?

A lot of important topics are being covered at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting. But physician and writer Elaine Schattner notes on Forbes.com that one of the most important may be around the design of clinical trials.

“For cancer patients trying an experimental drug, participating in a ‘matched’ study – using biomarkers, like genetics, to link their condition to a treatment – offers much greater chances of clinical benefit than does participating in a similar, unmatched study,” says Schattner. “In Phase 1 trials, a precision strategy boosted the response rate from 4.9 percent to 30.5 percent. The meta-analysis included 346 studies published from 2011 through 2013, a fairly recent data set, involving 13,203 research subjects.”

Schattner believes these results, and others like it, have the potential to upend our current clinical trials system. At the very least, it should get devotees of randomized clinical trials (RCTs), the current “gold standard,” to rethink their approach.

“Many doctors have intuited that matching cancer patients with drugs designed to target particular defects in their tumors makes sense,” says Schattner. “But until now, there’s never been proof that up-front “precision” yields superior clinical outcomes overall. Some might argue that this study, a meta-analysis, and any of the Phase 1 trials included, does not meet the level of knowledge or certainty offered by an old-fashioned, prospective and, ideally, double-blind RCT.”

Additionally, Schattner notes RCTs in oncology are expensive and require years of work by oncologists. Some of these studies comparing cancer treatments take so long they can be irrelevant by the time they are completed. RCTs can also be flawed in their design and analysis. She also argues that putting patients through a randomized Phase 3 trial could be equated to withholding the best care available.  

 IBM’s Watson Selected For Clinical Trial Patient Matching

IBM announced Froedtert & the Medical College of Wisconsin (MCW) Cancer Network will adopt Watson cognitive computing to help match cancer patients with clinical trials. The Froedtert & MCW Cancer Network is the first in Wisconsin and among the first cancer programs in the nation to use Watson for Clinical Trial Matching. The matching program is slated to begin this fall.

Finding and enrolling eligible patients in clinical trials continues to be a challenge for the industry, and less than five percent of cancer patients currently participate in trials. Watson for Clinical Trial Matching is designed to quickly complete the data-intensive process of matching patients with clinical trials, and provide doctors the information they need to advise their patients about relevant studies. For example, after a clinician submits a patient's unique health information, Watson will analyze the patient's data against clinical trial databases to provide clinicians with information regarding a patient's eligibility for a specific trial.

James Thomas, MD, PhD, oncologist and medical director, Froedtert & MCW Cancer Clinical Trials Office and Translational Research Unit, notes no two cancer patients are alike. "Watson will support a higher level of personalized care for our patients by enabling us to securely connect individual health information with a vast array of clinical trials,” he says. “By matching clinical trials to more patients with a high degree of precision, we believe Watson will help us fulfill our mission to advance the health of our community through scientific discovery."

IBM is working with Froedtert & MCW experts to implement a version of Watson for Clinical Trial Matching specifically for the Froedtert & MCW Cancer Network, which includes four locations in southeastern Wisconsin. As Watson progresses and matures through this collaboration, the solution will expand its body of knowledge with the goal of becoming increasingly efficient and attuned to the needs of Froedtert & MCW cancer patients.

European Commission Unveils 4 New Public Consultations On Clinical Trials

The Regulatory Affairs Professionals Society (RAPS) reports the European Commission (EC) has released four new consultations to deal with ethical considerations for pharmaceutical trials with minors, risk proportionate approaches in trials, summaries of trial results for non-specialists or “laypersons,” and definitions of investigational medical products (IMPs) and use of auxiliary medicinal products (AMPs).

The consultations offer respondents a chance to weigh in (comments on the four consultations are due by August 31, 2016) on updates to EC documents, particularly with regard to offering more information on how a risk proportionate approach to trials can be implemented and how documents can be aligned with current research.

Romanian Prosecutors Dismantle Illegal Pharma Testing Network

Business Review is reporting investigators from Romania’s prosecutor’s office are working on a complex case that involves the illegal testing of drugs in the country. Judges have issued search warrants for dozens of locations across the country, including the offices of family doctors in Bucharest and of companies active in the medical field. The authorities have also looked for evidence in 31 medical units across several counties, including Arges and Buzau.

“From the prosecution activities that have been carried out up to now, it has resulted that several employees in the medical sector have carried out illegal activities regarding some clinical trials that breached the law, which could have generated risks for the authorization process for drugs entering the market and negatively impacted the health of the population,” said the prosecutor’s office in a released statement. “Those people wanted to show up as having been treated in hospitals so as to submit requests for early retirement because of illness.”

In addition, the prosecutors have found a psychiatrist in Arad that used fictitious hospital admissions as a way to convince some people to enroll in the clinical trials. A doctor teaching at the university in the same city got resident doctors to break the law.