• The cost of drug development
  
• Insurance coverage for trials
  
• Paying to participate
  
• Traveling for treatment
  
• Lodging
  

The cost of drug development

Clinical trials are a big part of the high cost of drug development, and they're getting bigger. According to Getz, in the early 1990s, the average new treatment was tested in roughly thirty-two to thirty-six distinct clinical studies of all phases. By the late 1990s that number had grown to about sixty-eight. Note that these figures are not inflated by the growing prevalence of multi-center trials. A study conducted at a dozen sites is considered a single one of those sixty-eight trials. Getz explains:

Our research programs have gotten much more ambitious. The actual complexity of a protocol--the number of procedures that have to be conducted on a patient--has rapidly increased, by as much as 30 to 40 percent in a particular phase of research. The actual number of patients enrolled in a trial has gone up dramatically. In the early nineties, the average number enrolled was around 2,400 or 2,500 for a single new drug application. Now that number is approaching 3,800 or 3,900. It's also costing more to find patients. We're competing for patients with more studies, so we're using more aggressive, expensive, and sophisticated advertising and promotion today to find these patients.

Cancer trials tend to have more complicated protocols and they do tend to be more expensive. You're asking the patient to do more in the trial--more lab tests, to keep a diary, and to undergo more experiences with a study drug.

Payment for participation

Cash payments tend to be rare in NCI-sponsored trials, but are more common in trials sponsored by pharmaceutical companies. Payment tends to be higher in early-phase trials, which are more risky. Among trials that provide cash compensation, higher payments tend to be found in the more onerous trials, ones that require painful procedures or repeated visits. Don't expect to get rich participating in a clinical trial, though. Extremely high compensation would be considered unduly coercive, and is thus unethical. The amount of cash compensation you stand to receive should play little or no role in your decision about whether to participate in a given trial.

Drug-company profits

Insurance coverage for trials

You will not receive benefits for the following: Services and supplies which are experimental or investigational in nature; meaning any treatment, procedures, facility, equipment, drugs, drug usage, devices, or supplies not recognized as accepted medical procedure standards, and any such items requiring federal or governmental agency approval not granted at the time services were rendered.

No one has figured out a way of limiting the liability of the insurance provider in the event that the patient has a long-term adverse reaction to a study medication. A lot of it is due to the pharmaceutical industry's inability to educate the insurance providers as well as they could. Insurance providers need to understand who is going to bear the burden of that cost in the event that the patient requires additional care after the study has ended. Normally the pharmaceutical industry does pay those costs, although industry can be rather elusive in accepting that commitment. There are times where a patient might have had a pre-existing condition that may or may not have been exacerbated by the study medication.

There's an old adage in our industry: "Managed care and clinical research shall never mix." The greatest downside to that is that we're not improving the access that patients have to an investigational treatment that could potentially save their lives. But managed-care organizations are starting to realize that if they don't focus on demonstrating to the patient that they have their best interests in mind, they're going to lose that membership.

While this is very good news indeed, the agreement apparently does have a number of significant shortcomings. First, while the AAHP claims to represent about 1,000 managed-care organizations, not every HMO or PPO (preferred provider organization) is a member. Moreover, the agreement calls on AAHP merely to "encourage" managed-care plans to comply with the agreement, which does not have the force of law. In addition, even managed-care organizations that choose to comply with the agreement are being asked only to cover the routine costs of NIH-sponsored clinical trials, leaving in the lurch patients who wish to enroll in one of the many clinical trials sponsored by pharmaceutical companies.

But please don't despair if your insurance company or managed-care provider seems to exclude coverage for the clinical trial you wish to participate in. There are strategies that may well help you get them to pay for the non-experimental portion of your clinical trial, and as we've already seen, the study's sponsor typically pays for the experimental portion. Jane H. Bick, PhD, offers this perspective:

I don't believe that insurance companies should pay for the cost of research. I don't believe they should pay for data management or for the cost of investigational drugs. I do believe they should pay routine medical costs that they would pay anyway. They should not abandon a cancer patient who has the opportunity to go on a study.

Gregory T. David, a nurse coordinator at the University of California, San Francisco, and his colleague Robert L. Kuhn, a clinical research associate, point out that while they generally don't have trouble getting insurance companies to cover the costs of standard care, it's sometimes a challenge to convince an HMO to cover certain laboratory tests that must be performed outside the HMO's facilities.

Mr. David says of a current study:

This particular study is a combination of standard-care therapy and experimental therapy. It's up to the insurance company to understand that they're responsible for everything that's "standard of care." They're not financially responsible for anything else. The study picks up the costs of that. The problem is that much of the "standard of care" stuff has to be done here, which is "out of house" from their point of view. That's where the difficulty is in getting insurance companies to go along. It usually just takes a little more time, a week or two weeks, to get them to play. It requires careful documentation, careful communication between us.

The trial sponsors do not require us to have all these assessments--lab tests, radiology assessments, and so on--at our own institution. The HMOs generally want to do as much as they can in house, because it's less expensive for them. They will authorize us to treat the patient here. The patients receive their chemotherapy here, and they'll have their periodic visits with our oncologist here, and sometimes because of necessity we will do lab work on the day of treatment. But follow-up tests to monitor blood count, liver function, adrenals, and things like that will be done at the HMO.

Sometimes clinical trials are not new drugs. They're new combinations of existing drugs. But the minute you say "clinical trial" or "investigational therapy," they say, "Sorry, we're not going to cover anything here." Therefore many people are participating in clinical trials, and if it's not a brand new drug, their insurance companies don't know it. Never ever use the words "investigational drug" or "experimental" or "clinical trial" with your insurance company. It's like fanning the fire.

Under the old days of fee-for-service insurance, insurers never asked what drugs you were being given, what frequency, what dosage, whether you were an in-patient or an out-patient. They didn't ask for details--they just paid the bills. So people were participating in clinical trials without much objection from their insurance companies. Now, under managed care, payers want to know everything. Then they look at their little protocol sheets, and see that this is not one of the approved protocols, and they deny care.

Even if your insurance company or HMO explicitly denies care, you still shouldn't give up, says Jane Bick.

It's so hard to fight the disease, and your family is in a state of shock. How can you fight your insurance company when you're fighting the disease? But you have to fight, because it's about survival.

If you want to enter a clinical trial for a medication that has already been approved for another condition, or at a different dosage, you can often invoke your state's "off label" law. Not all states have an off-label law, but those that do permit physicians to prescribe at will any medication that's been approved for use in one situation. If this is the case, your insurance company may not need to know that you're participating in a clinical trial. You'll simply submit your bills for reimbursement just as you would for any other medical treatment.

"Treatments or medications already approved by the FDA would usually be covered by HMOs," she says.

I remember one instance where there was a patient who wished to participate in a cancer clinical trial, and the HMO was denying treatment. I wondered what I could do to prove to them that this was something that had been used before, and had been covered. I actually found a lawsuit that was won by a patient in California for the same treatment. I found enough documentation to prove to the HMO that this would really benefit the patient, and they should not deny it.

When you have a drug that's not approved for your diagnosis, the insurance company can say, "Well, it's experimental, and we're not going to pay for it." That was my experience with interferon in 1989. Fortunately, there was quite a bit of literature on interferon, and the manufacturer provided me with abstracts of literature citations showing use in my condition. I also managed to get a printout of all the interferon claims that had been paid by the same insurance company and a letter from my doctor explaining my need for this drug. I submitted a request for reconsideration, and supported it by the thick stack of documents I had gathered, particularly pointing out that they had approved claims for this drug for others. They ended up paying for my treatment.

Go public. Insurance companies fear only two things: a court of law and the court of public opinion. And a lot of pressure can be brought to bear on insurance companies through the media and through attorneys. If they know that you've talked to attorneys and that you're talking to the media, all of a sudden they reconsider. There are attorneys who will take these cases either on contingency or for a small fee. Sometimes all it takes is one letter from a law office, and all of a sudden the insurance company says, "We'd better pay attention to this one."

Legislative action

And it's short-sighted on the part of the insurance companies and managed-care organizations as well. The quicker new and better treatments for cancer are developed, the more money they will save. New treatments are likely to be more effective and have fewer side effects than the old ones, requiring less medical care for those who receive them. Health insurance companies should be encouraging their members to investigate clinical trials instead of placing obstacles in their paths.

But this argument often falls on deaf ears in the insurance industry. If the industry won't voluntarily cover the standard medical care associated with clinical trials, we'll all have to encourage our elected representatives to pass laws that will force the industry to do what's right. As of this writing three states--Maryland, Rhode Island, and Georgia--have enacted laws mandating coverage for some kinds of clinical trials. Similar laws have been proposed in several other states and at the federal level as well.

Maryland's law is the most comprehensive. Passed in 1998, it requires insurers to pay "the cost of a medically necessary health care service that is incurred as a result of the treatment being provided to the member for purposes of the clinical trial." It specifically excludes payments for the cost of the investigational drug or device or any costs involved in administering the clinical trial.

The law covers trials in Phases I, II, III, and IV for people with cancer, but only Phases II and III for people with other life-threatening diseases. To be covered, the trial must be approved by the National Institutes of Health (NIH) or one of its cooperative groups, the FDA, or the federal Department of Veterans Affairs. The law also covers trials conducted by academic medical centers in Maryland. The law states that insurers must pay for patient costs incurred in trials for which "there is no clearly superior noninvestigational treatment alternative; and the available clinical or preclinical data provide a reasonable expectation that the treatment will be at least as effective as the noninvestigational alternative."

In Rhode Island a similar law is restricted to Phase II and III clinical trials for cancer.

Jane Bick was instrumental in getting Georgia's law passed in 1998. This law requires health insurers (but not companies that self-insure their employees) to cover the routine medical costs for children enrolled in Phase II, III, and IV cancer trials.

It only covers children because we were told that was all we could expect to get passed in the '98 session. Georgia is a strong pro-business state, and it has a very active insurance lobby. They fight everything, and their mantra is, "If you pass this, it'll raise premiums, and many more small businesses in Georgia won't be able to insure their employees. That's simply not true, especially for cancer clinical trials. Insurers already pay routine medical costs for standard therapy. This bill was to prevent payer abandonment of kids in studies."

As a board member of CURE Children's Cancer, Bick managed to assemble a coalition of other cancer organizations to help push for the bill's passage. Among the people she recruited was Mo Thrash, a former CURE president who is also an experienced lobbyist with intimate knowledge of how things work in the Georgia legislature. Thrash (who had lost one of his children to leukemia twenty years previously) was able to get the ear of important legislators. He was also able to give valuable advice on encouraging public support for the bill, such as when to have people call their senators and representatives. Bick herself coordinated the strategic appearance of, as she puts it, "cute, bald-headed kids."

Legislators can't fix problems if they don't know the problems exist. I hate to talk in clichés, but one of the things we found was that squeaky wheels get greased. We had so many phone calls going into the Georgia legislature that legislative staff members were saying, "What is this bill? It must be an important one."

At the federal level, broad access to clinical trials was an important part of a bill called the Patients' Bill of Rights Act of 1998, introduced by Senator Thomas A. Daschle (D-SD) in the Senate and by Congressman John Dingell (D-MI) in the House of Representatives. The bill would have required that any health insurer cover the "routine patient costs for items and services furnished in connection with participation" in a clinical trial for anyone who has "a life-threatening or serious illness for which no standard treatment is effective." The bill would have covered all phases of clinical trials as long as it was a trial approved by the National Institutes of Health or its cooperative groups, the Department of Veterans Affairs, or the Department of Defense.

Unfortunately the bill never emerged from committee in the 105th Congress, but its supporters vowed to reintroduce it in the next Congress. Perhaps by the time you read this book we will have comprehensive federal legislation guaranteeing patients access to clinical trials.

But if such legislation has not yet passed, and if you believe health insurance providers should be required to cover the routine medical costs of patients enrolled in approved clinical trials, contact your state and federal representatives. All it would take would be a short, polite letter, a phone call, or an email citing the importance of clinical trials, and urging the representative to support appropriate legislation. If you're more ambitious, if you have specific legislative savvy, or if you're involved with a cancer society, you may wish to follow Jane Bick's lead, and help organize a broad-based coalition of organizations to lobby your state legislature--or the US Congress--for passage of a specific bill.

Paying to participate

• If you have money saved for a rainy day, that day has come.

• You may be able to withdraw cash from retirement or pension accounts.

• Gain access to the equity in your home by taking out a second mortgage or a reverse mortgage.

• If you have life insurance, you may qualify for accelerated death benefits or a viatical settlement. In an accelerated death benefit the insurance company pays you a percentage of the value of your policy before your death. Viatical settlements are cash lump sums given by investors to terminally ill people in exchange for the death benefits of their life insurance. For more information on these options, go to: www.viatical-expert.net.

• Have your friends or co-workers organize a fund-raiser to help you pay for your treatments.

• Try to interest local newspaper or television reporters in writing or broadcasting stories about your plight.

• Some organizations offer financial aid to people with cancer. For example, the Leukemia Society of America offers patients up to $750 per year in reimbursement for such things as travel, approved drugs, blood transfusions, or x-rays. LSA will only reimburse expenses incurred after you have applied for aid. Call (800) 955-4LSA. The National Children's Cancer Society, Inc. also provides some financial assistance. Call (800) 5-FAMILY.

• Check with your church or any fraternal organizations to which you belong; many of them maintain funds for members to use in emergencies.

Throughout this discussion we've been talking about the typical situation in which a clinical trial's sponsor pays for any investigational treatment, and the patient or her insurance company pays only for the routine medical care associated with that treatment. In recent years, however, a small number of for-profit companies have sprung up in the US that charge people large sums of money for the privilege of participating in clinical trials.⁴ Some of these companies have charged people with cancer as much as $30,000 to receive investigational treatments.

While such practices have been defended as being necessary for researchers who are unable to obtain research funding by other means, I believe that people with cancer should be exceedingly wary about pursuing fee-for-service research. The ethics of such a practice are questionable at best, and it would be difficult to separate serious and principled researchers who are merely using an innovative funding technique from snake-oil salesmen who are intent on exploiting you for their selfish enrichment.

Traveling for treatment

Travel presents both financial and logistical problems for a person with cancer and his or her family. Fortunately there are solutions to most of these problems.⁵

If you need to travel for a clinical trial, the first thing you should do is to check with the people running the trial to see if the trial itself will cover some or all of your travel expenses. This is a common practice, whether the trial is in your own city (in which case you may be able to get your taxi fare reimbursed), or somewhere far away. Dr. Richard Gams confirms this practice:

If our study required patients to make an additional trip that wouldn't help them particularly, but is necessary to learn something about the drug, then often it's considered appropriate not only to pay for the test, but to reimburse the patient for travel expenses.

Air travel

Mercy Medical Airlift (MMA) coordinates three sectors of charitable air services in the US--the corporate aviation sector, the private aviation sector, and the commercial airline sector. MMA uses fixed-wing aircraft to help financially needy patients go to and from care centers for scheduled appointments, but it does not provide emergency transport. Mercy Medical Airlift can be contacted at (800) 296-1191.

The corporate aviation sector includes 750 corporations who are part of the Corporate Angel Network. Participating companies allow cancer patients to use empty seats on regularly scheduled corporate flights. You need not demonstrate financial hardship to use this service, and there's no limit to the number of trips you may take. Adult cancer patients may travel with a single companion, and children may be accompanied by two parents. Call (914) 328-1313 for more information.

The private aviation sector includes 4,500 pilots and 32 volunteer pilot organizations across the US who use their own time and aircraft to fly patients free of charge to care centers. These groups are part of the Air Care Alliance. Call (888) 662-6794 for more information.

In the past some commercial airlines have occasionally offered special fares or even free tickets for people who must travel for medical care. Unfortunately, such programs are becoming increasingly rare. Contacting the airline directly through its reservations desk will generally prove unproductive, so it's best to work through MMA when pursuing this option.

Ground transportation

Lodging

The ACS maintains Hope Lodges in many major cities that provide free housing on a first-come, first-serve basis for people being treated for cancer and their families. Hope Lodges have kitchen and laundry facilities. For information, phone (800) ACS-2345.

The National Association of Hospital Hospitality Houses maintains a list of facilities set up to provide free or low-cost housing to patients being treated at nearby hospitals or their families. The houses range in size from six to sixty-four rooms and typically have a common living area. Most have kitchens and laundry facilities as well. For information, phone (800) 542-9730.

The Ronald McDonald Houses sponsored by the McDonald's Corporation offer lodging to children and their families traveling for medical care. You may need to demonstrate financial hardship to be permitted to stay at some facilities. Others charge a nominal fee of $10 per night, which may be waived if you can demonstrate financial hardship. For information, phone (312) 836-7100.

The National Cancer Institute (NCI) offers meals and housing in its Children's Inn for patients under 18 being treated at NCI. Family members can be accommodated on occasion. For information, phone (800) 4-CANCER.

Family members of people being treated at NCI are sometimes permitted to stay overnight in the patient's room. You should verify the availability of this option when making arrangements, and again with the nurses on your floor.

Many hospitals make individual arrangements with nearby hotels for reduced rates for the families of patients. Check with the hospital's social worker or admitting desk for more information. Additionally, some major medical centers, such as the Johns Hopkins Medical Institutions in Baltimore, maintain outpatient facilities for patients and their families.

Notes:

1. Donald Drake and Marian Uhlman, Making Medicine, Making Money (Kansas City, Missouri: Andrews and McMeel, 1993): 5-9.

2. "The Right Prescription," Fortune, 21 December 1998, 76.

3. Robert Peer, "Managed-Care Plans Agree to Help Pay the Costs of Their Members in Clinical Trials," The New York Times, 9 February 1999.

4. Stuart E. Lind, "Financial Issues and Incentives Related to Clinical Research and Innovative Therapies," in Vanderpool, The Ethics of Research, 185-202.

5. This discussion owes a great deal to the excellent chapter on traveling for care in: Lorraine Johnston, Non-Hodgkin's Lymphomas: Making Sense of Diagnosis, Treatment, and Options (Sebastopol, California: O'Reilly & Associates, 1999).