Right-to-Try Law Aims to Aid Terminally Ill Texans
Public Health Feature — July 2016
Tex Med. 2016;112(7):33-38.
By Joey Berlin
Houston gynecologic oncologist Charles Levenback, MD, says Andrea Sloan, whom he treated at MD Anderson Cancer Center for about seven years before she died on Jan. 1, 2014, was a remarkable, courageous exception among cancer patients.
Dr. Levenback was a fellow at a New York hospital during the AIDS crisis of the 1980s. The AIDS patients of that pivotal time, he says, intensely pursued any avenue to find a treatment or cure for their disease, doing so with a fervor Dr. Levenback says cancer patients just haven't approached.
"They really went to extraordinary lengths, and they were very angry, and angry with the way they were treated," he said of the patients during the AIDS epidemic. "Cancer patients have not gone there. And, also, cancer advocacy groups have generally not gone there."
But Dr. Levenback says Ms. Sloan, a beloved lobbyist at the Texas Capitol, was different. After vocally publicizing her battle to obtain an experimental drug — with a group called Andi's Army working toward that cause — Ms. Sloan died of ovarian cancer at age 45, about two months after finally starting an experimental treatment.
"She was the kind of person who didn't want to take no for an answer," Dr. Levenback said. "I really admire her for [being] willing to put herself out there and draw attention to all of this."
Ms. Sloan's story helped inspire a "right-to-try" law the Texas Legislature passed last session in an effort to make experimental drugs more accessible to terminally ill patients. Gov. Greg Abbott signed that measure, House Bill 21, on June 16, 2015.
Rep. Kyle Kacal (R-College Station), who sponsored HB 21, says the bill provides expedited access to investigational drugs to cut through the bureaucracy some patients like Ms. Sloan have faced when pursuing them through the U.S. Food and Drug Administration's (FDA's) compassionate use exemption.
"Terminal patients, they don't have weeks, months," Representative Kacal said. "They've got a short window of opportunity, and if the drug is out there that has good science and passed that first part of FDA approval, let's go [try it]."
Lost Loved Ones Prompt Action
Representative Kacal says the collective impetus for HB 21, in addition to Ms. Sloan's death, was the deaths of his own mother and the mother of Rep. Ken King (R-Canadian), another of the bill's sponsors. All three women died from ovarian cancer. The legislators' mothers died about 40 days apart in 2013.
HB 21 allows a patient with a terminal illness to access an "investigational drug, biological product, or device" if the patient's physician has considered all other FDA-approved treatment options and determined those options are "unavailable or unlikely to prolong the patient's life." The patient must sign an informed consent form before receiving an investigational drug.
The bill says the manufacturer of such a drug may make it available to the patient, but the manufacturer isn't required to do so. If the manufacturer does make it available, it must do so "without compensation."
HB 21 defines an investigational drug as one that successfully completed Phase I of a clinical trial but is still under investigation in the trial and isn't yet FDA-approved. In Phase I of a trial, researchers evaluate the drug for safety and proper dosing.
The law's eligibility requirements are similar to those of the FDA's Expanded Access policy, also known as compassionate use. The federal policy allows patients to qualify for access to an investigational drug when they and their licensed physicians are willing to participate in the treatment, according to the agency's Expanded Access page. Patients must:
- Have a serious or life-threatening disease or condition;
- Have no comparable or alternative therapy available to diagnose, monitor, or treat their disease or condition; and
- Be unable to obtain the drug through another FDA application channel or to participate in a clinical trial.
Austin oncologist Debra Patt, MD, past chair of the Texas Medical Association Committee on Cancer, says HB 21 effectively gives cancer patients options when standard treatments are no longer available and they can't participate in a clinical trial. But Dr. Patt says patients should use that option infrequently because a clinical trial, if available, is the best setting in which to try experimental drugs.
"For most patients who receive treatment, it really should be under evidence-based care that we believe is more likely to be effective and less likely to have substantial harm," Dr. Patt said. "When patients are taking experimental therapies, those kinds of experimental therapies really are best suited for use within the guidance and oversight of a clinical trial, so … the use of that drug is being clearly evaluated to gain understanding of the drug's efficacy or toxicity in patients.
"I do think that this is important legislation, and it's really important to allow doctors and patients to make the right decisions with regard to their care. I praise Representative Kacal on the efforts to push this forward because I do think it's important," Dr. Patt added. "But I think it is in the best interest of patients if it's used extremely infrequently."
The Goldwater Institute, which supports right-to-try legislation across the country, maintains the website http://righttotry.org. In May, the site said 28 states now have right-to-try legislation, and 23 others were considering such a law this year.
Ms. Sloan made national news in 2013 as she sought to obtain an unapproved drug known as a poly ADP-ribose polymerase (PARP) inhibitor, a class of drugs Dr. Levenback says looked promising as a treatment for cases like hers. Ms. Sloan was a carrier of a mutated gene known as BRCA, associated with an increased risk for breast and ovarian cancer. Dr. Levenback says the belief was patients with that gene might respond better to PARP inhibitors than other therapies.
"We were getting to the point where we were exhausting the other standard treatment options," Dr. Levenback said. "She had multiple operations, she had radiotherapy, and she had additional chemotherapy. Not only that, the number of research studies with PARP inhibitors was growing, so time became more urgent. But there were no clinical trials at MD Anderson that she was eligible for. At this point, she was seeing me as her primary doctor but also some other oncologists at MD Anderson, and we agreed that a PARP inhibitor would be good for her."
FDA approved Ms. Sloan's compassionate use request, but the agency can't require a drug company to provide the patient access to a drug. The one Ms. Sloan initially approached for access to a PARP inhibitor, BioMarin, refused to provide it, leading to public outcry during summer 2013 and a large online movement on Ms. Sloan's behalf. In early October 2013, Ms. Sloan announced another drugmaker, which requested anonymity, agreed to provide her a drug similar to the one she had sought from BioMarin.
But bureaucracy prevented Ms. Sloan's treatment from beginning right away. For an emergency case in the FDA's compassionate use program, the physician can request and receive authorization over the telephone or other electronic communication, and treatment may start immediately upon approval.
For nonemergency cases, treatment may begin 30 days after FDA receives the application to use the drug if the physician doesn't hear from the agency in the interim, according to the FDA website.
Still, it's not as simple as getting a federal sign-off to begin treatment.
"You have three parties, basically: the FDA, the drug company, and in our case, MD Anderson," Dr. Levenback said. "All three groups need their documents to satisfy specific things; there have got to be contracts; and there have got to be lawyers, human experimentation committees, so all of that took several weeks."
Dr. Levenback says Ms. Sloan began taking the investigational drug about a month after the anonymous pharmaceutical maker agreed to provide it to her.
"Just before she died, we had a scan result that suggested that she was in fact responding," he said. "But she was kind of debilitated by the whole process. She was in much better condition when we first asked [the second company], when she ultimately got the drug."
The Best Route?
Representative Kacal says HB 21 expedites the waiting period that can emerge from the usual bureaucracy involved with compassionate use.
"In my opinion, based on the eligibility, this takes that long period out of the equation," he said. "If the drug's already passed that first stage of FDA approval, and the patient and the doctor agree that this is the right path for them, it's available now. That's huge."
Representatives Kacal and King's personal interest in the disease also led them to start the KK125 Ovarian Cancer Research Foundation. A bill Representative King introduced, HB 2813, that became law in May 2015 requires insurance coverage for a blood test that could be a marker for ovarian cancer. (See "Bill Requires Coverage for Possible Cancer Indicator.")
Dr. Levenback says he doesn't see analysis of what happened in Ms. Sloan's case as "a finger-pointing exercise," noting all parties involved want the same thing: to get patients access to novel treatment before they die. But there are many different factors and interests to consider, he says.
"For the drug companies, they're trying to protect themselves, protect their intellectual property. The chance of getting a drug approved is so slim, and the investment is so big, they don't want to do anything to upset that apple cart," Dr. Levenback said. "[For] MD Anderson, this is basically an experiment with one person, so we have to abide by all the regulatory stuff, [and] you just can't write a prescription. Then the insurance companies, what are they going to pay for, what should they or should they not pay for? In this case, it's a little easier because the drug is provided for free by the company, but there's all the other standard care, which can get pretty expensive, especially when hospice might be the alternative."
At a Texas Senate Health and Human Services Committee meeting last spring that examined a similar bill, Sen. Charles Schwertner, MD (R-Georgetown), raised "concerns that vulnerable individuals could be hurt by the law," according to an Austin American-Statesman report. Senator Schwertner said at the hearing he worried physicians and drug companies might "sell hope" using unproven medications.
"History is replete with snake oil salesmen in the medical field," he said.
Gynecologic oncologist Lois Ramondetta, MD, chair of TMA's Committee on Cancer, says she's concerned that it's "always easier to give another drug than really sit and talk with someone about advanced care planning, for both the patients and the physicians, to avoid the elephant in the room and the fact that the end of life is coming."
"I would say it's very important to recognize that more drugs [are] not always better and can in fact sometimes even shorten life," she said. "Really, with the speed at which new drugs are discovered, they need to be evaluated carefully before being used."
Thus far, Dr. Levenback says, HB 21 has helped the most by raising awareness of the availability of experimental therapies. He says he doesn't know whether it's gotten any easier for patients to obtain access to investigational drugs; none of Dr. Levenback's other patients have applied for compassionate-use access since HB 21 was enacted.
FDA typically grants the vast majority of single-patient requests for expanded access, according to agency reports, and granted more than 1,100 such requests between October 2014 and September 2015. (See "Expanded Access Use.")
MD Anderson's patients are fortunate, Dr. Levenback says, because the center has the research nurses who can deal with drug company paperwork and attorneys "who are used to dealing with the contracts, the FDA regulatory environment."
"For an oncologist in practice in a community hospital or a private practice or something like that, who doesn't have all this, how is a doctor going to spend the hours and hours it takes us filling out forms and getting all that stuff to do all of this?" Dr. Levenback said. "For us, it's the cost of doing business. But for a lot of places, there's just no time and money for that."
In December 2014, FDA announced the first approval of a PARP inhibitor, granting accelerated approval to the drug olaparib for ovarian cancer patients with specific BRCA gene abnormalities who have gone through at least three chemotherapy regimens. Dr. Levenback says he has "a couple" of patients taking a PARP inhibitor through that channel.
Dr. Patt says it's important to heighten awareness of novel therapies but says "any variation from what's known to be safe and effective should have careful consideration between patients and the doctors who treat them." She notes the possibility that an experimental therapy taken outside a clinical trial could undesirably shift the focus of care in the patient's final days.
"Let's say I gave them experimental therapy that I didn't know was going to work, and then they got so sick that they had to go in the hospital instead of being at home and having time where they felt better, where they were with their family," she said. "You can see that might be an opportunity missed."
But anything that shines a light on the complexity of the health care system is a good thing, Dr. Levenback says. He asks why it's so hard for a patient like Ms. Sloan to gain access to potentially life-extending therapy when good science provided evidence the drug could help.
"Andrea paid her taxes, she was insured, she was a good servant of society, she was responsible, and now she's asking back for a drug [that's] not going to cure her but maybe prolong her survival," he said. "And it felt like everything was conspiring to keep her away from it."
Joey Berlin can be reached by phone at (800) 880-1300, ext. 1393, or (512) 370-1393; by fax at (512) 370-1629; or by email.
Bill Requires Coverage for Possible Cancer Indicator
Rep. Ken King (R-Canadian), one of the sponsors of House Bill 21, also backed another new law designed to foster greater preventive screening for ovarian cancer.
Representative King introduced House Bill 2813, which requires qualified health plans to cover cancer antigen (CA) 125 blood tests. An elevated level of CA 125, a protein, may be an indicator of ovarian cancer.
Representative King says he introduced the bill because of the value of early detection and the possibility a woman could save her life with a covered test at her well-woman exam.
"While most doctors and most professionals will agree that the CA 125 is not 100-percent accurate, they'll also tell you at the same time neither is a PSA [for prostate screening], or neither is a mammogram, or neither [are] these other tests that we pay for," Representative King said.
The Mayo Clinic says the CA 125 test isn't accurate enough to screen all women for the disease because "many noncancerous conditions can increase the CA 125 level." Gynecologic oncologist Lois Ramondetta, MD, chair of TMA's Committee on Cancer, says the CA 125 is "an amazing test for following patients who we already know have ovarian cancer. But it is not a very good screening test used by itself and in premenopausal women."
"There are specific times that a CA 125, used in combination with other screening tests, is useful, and my recommendation is always to only order a CA 125 in partnership with your physician, who has discussed the risks and benefits with you," she said.
Gov. Greg Abbott signed HB 2813 on May 25, 2015.
Representative King says the point of the law is "the more women who get tested, the more data that the researchers are going to have [and] a better chance we're going to have in finding drugs that work and possibly a cure."
July 2016 Texas Medicine Contents
Texas Medicine Main Page