BY VICTOR THURONYI
I often hear complaints that not enough patients are signing up for myeloma clinical trials. A common remedy is sharing information to encourage patients to participate. While this is good and necessary, I think that further steps could be taken that would increase trial accrual and therefore speed up the process of completing trials and getting information published so that new drugs and drug combinations can be tested in time – especially in time for already diagnosed patients whose time (like mine) is limited.
These ideas are not necessarily in order of importance. I also recognize that some may be easier to implement than others, and that as with most public policy ideas they may appropriately be modified after discussion with experts and stakeholders. So this is a first crack at identifying some potential solutions. One good thing is that many of these ideas can be implemented independently – together they should make a major impact, but even if a few are adopted they will constitute an improvement.
Some of these ideas are applicable to cancer trials other than for myeloma or for clinical trials in general. If application to all clinical trials is not feasible ASAP, then myeloma can be used as a pilot to get some of these ideas off the group and in operation quickly.
- Review inclusion and exclusion criteria. One of the reasons that patients don’t sign up for a specific trial is that they do not qualify since they do not meet an inclusion criterion or are thrown out based on an exclusion criterion. Trial designers should be vigilant to formulate these criteria so as to maximize the number of eligible patients, without of course affecting too much the smooth running of the trial or the scientific validity of the results. One particular pet peeve of mine is the required M-spike. Many trials nowadays require an M-spike of 0.5 g, but there are a few trials requiring 1.0. I am questioning whether the 1.0 is really necessary, and could we use the lower level unless there is a compelling reasons to use 1.0.
- Transparency on trial details. Patients researching trials on clinical trials.gov (or using SparkCures) get a lot of information, but for those seriously considering a particular trial, there is further detailed information on the Research Consent Form for the trial. The FDA should require all FDA-approved trials to include a link to the Research Consent Form on www.clinicaltrials.gov.
- Keeping clinical trials.gov information updated. Somewhat shockingly, there is no guarantee that information on clinicaltrials.gov is up-to-date. Particularly important is information on whether the trial is currently recruiting, and information on the sites where the trial is being run. The FDA should make sure that this information is kept up to date. This can be done by legally mandating updating and, equally important, hiring some staff members who will watchdog the website and make sure that the updating is getting done. This requires hiring a few people with intermediate level skills. They should be calling those investigators who have not done the updating in time. This would require a little bit of a budget but surely a drop in the bucket compared to the overall expense of clinical trials. It could have a big impact on patient accrual, because patients would then have confidence that the information they are seeing is current. (Editor's Note: To get around this current limitation, the Myeloma Crowd has partnered with SparkCures, who manually updates all trials on their system to ensure they are open and current)
- Require all trials sites to be listed on clinicaltrials.gov. The FDA should require all trials to list on clinicaltrials.gov all the sites that are recruiting or are expected to be recruiting in the near future, so that patients can figure out what trials are convenient for them.
- Require insurance coverage for clinical trials. The Affordable Care Act should be amended if needed to require insurance companies to cover all expenses of clinical trials that are billed as part of the standard of care for trials that take this approach (with no deductible or copay). Given that the number of patients on clinical trials is relatively small, this should not be a budget buster for insurance companies, but it should have a positive impact on enrollment since it would make trial participation a more affordable option for patients. Possibly funds could be paid to insurance companies by the government to cover the additional costs.
- Medicare/Medicaid coverage. I am not sure whether there are issues here. The policy should be that all clinical trials need to be required to accept Medicare and Medicaid for any costs that are to be billed to the patient, so that there is full coverage and no out-of-pocket cost to the patient. If that is the current situation, great, and if not, it should be.
- More trial sites. The number of patients expected to be accrued at a particular site should be limited so that the expected accrual time would be fast. And there should be a requirement for geographical diversity, so that more patients would have convenient access to more trials. This is particularly important for myeloma and perhaps cancer trials in general. The reason is obvious – with more sites, patients can be accrued faster. At the same time, there is a benefit in terms of cost and clinical benefit to keeping the number of sites for trials down so that each site has a large enough number of patients to cover the cost of running the trial and to take advantage of experience that the people running the trial have with patients and managing their side effects. So some balancing of these interests should be involved. By expanding the number of sites, accrual rates should be increased dramatically.
- Design trials so that all arms provide a good treatment approach. To the extent possible, trials should be designed so that all treatment arms provide a good treatment approach. This means for example avoiding placebo and avoiding single agent trials, at least for myeloma where single agents are rarely as effective as a three-drug combination. Even in a phase I trial, where you are testing dosage (minimum tolerated dose) wouldn’t it make sense to test that dosage as part of a three-drug combo given that you pretty much know that in all likelihood the drug is in fact going to be used in a three drug combo in the clinic after approval? If all treatment arms represent plausible best shots at therapy then patients will not be turned off a trial because it gives them less desirable treatment than they could get outside of a trial. Designing trials in this way will take some creativity. Perhaps the approach could be confined to myeloma trials as an experiment, especially given the experience in myeloma that single agents tend not to work. I am confident that smart scientists can figure out trial designs that accommodate this constraint while providing valid scientific results.
- Facilitate patient communication on trial eligibility. It is difficult in the case of some centers for patients to find out whether they are going to be eligible for a particular trial. To the extent possible, centers should be willing discuss with patients over the phone eligibility criteria, at least to rule out those patients that are not going to qualify. And centers need to be as transparent as possible with patients. This may require additional investment in nurse trial coordinators. It may also benefit from a coordinated or intermediary approach, whereby a patient would give their information in detail to a patient advocate who would then shop around for various trials and identify possible oncs where the patient looks to be eligible, at least as a first crack. In short, centers need to make it easier for patients to find out whether they are likely to be eligible.