New Strategies Needed to Boost Clinical Trial Accruals

MARINA DEL REY, Calif--Clinical researchers must develop strategiesto cope with the various obstacles faced by patients and physicianswho want to participate in research trials, said oncologists atthe Association of Community Cancer Centers (ACCC) economics conference.

Because most health insurance plans generally prohibit membersfrom participating in trials, the number of patients enrolledin studies has declined dramatically in recent years.

Unfortunately, it is axiomatic in clinical trials management that"clinical trials are rarely self-supporting," said CarlG. Kardinal, MD, associate director, Ochsner Cancer Institute,New Orleans.

When institutions were profitable, they were willing to make upthe costs, so they could attain the Community Clinical OncologyProgram (CCOP) designation, Dr. Kardinal said.

But with managed care, funds are drying up. Research personnelare viewed as "non-revenue-generating," he said andmay become the "silent casualties" of cost-cutting efforts.

Cary A. Presant, MD, president, California Cancer Medical Center,West Covina, noted that in California the problem of accrual hasbecome so severe that the number of CCOPs in the state has droppedfrom 7 to 3--and one of those is at Kaiser Permanente (an HMO).

Through his experiences in southern California, Dr. Presant hasobserved several reasons for the increasing difficulty in accruingpatients for clinical trials.

1. In the past, there was a "tacit agreement" that insurerswould allow their members to participate in trials, as long asthe expenses "didn't make them raise their eyebrows,"Dr. Presant said. But now, nearly all plans have a strict prohibitionon clinical trials.

2. Physicians have become so busy trying to deal with contractingand maintaining relationships with primary care physicians thatthere is simply less time left at the end of the day for clinicalresearch activities.

3. Eligibility criteria are becoming more restrictive, decreasingthe number of patients available for trials. "When we finallyget to an eligible patient, he or she may be in an HMO that won'tenter patients into clinical trials," Dr. Presant said.

4. The managed care system is fluid, in that patients change healthplans often, either by choice or because their employer changesinsurers, making follow-up of patients on trials difficult.

5. Accrual is more difficult for certain types of trials thanfor others. Dr. Presant said it was not difficult to enroll HMOpatients into an Adriamycin/cyclophosphamide dosage trial or anMRI study measuring tumor uptake of fluorouracil that was fundedby the NIH and passed on no additional charges to the HMOs.

Studies that have encountered difficulties in getting approvalfrom HMOs include expensive treatments, such as bone marrow transplants,those involving investigational drugs (phase II trials), and cancerprevention studies.

Working With Payers

"We all have a responsibility to work with payers to gainacceptance of clinical research trials," Dr. Presant stated.He suggested that protocols need to be reviewed for simplicity,in terms of the number of tests or follow-up, so that payers areassured that only the absolutely necessary data will be collected.

Dr. Presant also suggested that oncol-ogists begin dialogues withmedical directors in primary care and HMO settings, to ascertainthe types of clinical trials they see as beneficial or usefuland would not automatically deny.

He added that it is important to stress to primary care physiciansthat, in many cases, patients would get the same follow-up onthe clinical trial that they would get if undergoing traditionalchemotherapy outside a trial. However, when potential side effectsof the study treatments necessitate additional monitoring or hospitalization,funds to cover these costs will have to be obtained from otherresearch pools.

Dr. Presant urged oncologists to include cost-effectiveness analysesin their study evaluations. "If we can show saved admissionscosts or return to home environment sooner with new treatmentprograms, they will be more readily accepted by HMOs," hesaid. (See below.)

Support Legislation

Along with these actions, Dr. Presant said oncologists need toconsider supporting legislative mandates that would make it illegalfor insurance companies to deny payment for the routine-care costsof their members who enter approved clinical trials.

A bill with this provision was passed by the California StateAssembly and Senate, but was vetoed by Governor Pete Wilson. Hisstated reason for the veto--and a potential threat to similarlegislation in other states--was that it could not be appliedto so-called ERISA plans (self-insured, employer-sponsored planscovered at the federal level by the Employee Retirement IncomeSecurity Act).

Exemption from this requirement could offer a competitive advantageto companies able to self-insure.

As an alternative, Dr. Presant said, legislation could be passedrequiring every third-party payer or self-insured plan to devotea percentage of the dollars in the plan to patients who enterclinical trials, or to donate those dollars to clinical investigationactivities.

Economic Analyses Critical to Accrual

For Rodger J. Winn, MD, the first step toward getting approvalfor HMO patients to enter clinical trials is to prospectivelycost out the protocol expenses, so as to arrive at a fairly accurateestimate of the incremental costs.

In his presentation at the ACCC meeting, Dr. Winn, chief of theCommunity Oncology Program, M.D. Anderson Cancer Center, saidthat once you know these marginal costs, "some medical directorsare willing to talk." He noted that in trials sponsored bypharmaceutical companies, these incremental costs should not bepassed on to third-party payers.

Dr. Winn also gave an example of the type of cost-effectivenessanalysis of proposed trials he would like to see done.

If one arm of a lymphoma trial, for example, costs $50,000 andthe other $150,000, and 100 patients are placed on the more expensiveprotocol, the difference in the cost of the two treatments wouldbe $10 million. Outcomes data can then be used to help determinewhether this is money well spent.

If the study hypothesis is that the cure rate will go up from20% to 50% and those cured will live an average of 35 additionalyears, then the $10 million has gained 1,050 additional life-years.This calculates to $10,000 per year of additional life. "Nota bad buy," Dr. Winn said.