So, you are a hero and have decided to participate in a clinical trial. We all are deeply in your debt, so I want to start out and extend to you a very big thank you.

Making that decision to participate in a clinical trial isn’t an easy decision for anyone. Participating in a trial means you might be subjecting yourself to side effects, toxicities as well as possibly not receiving or delaying having the current standard of care. Participating in a clinical trial, no matter if it’s a prostate cancer clinical trial, or any other type of trial, comes with inherent and unknown risks.

There has been some recent discussions suggesting that sponsors of trials should work to reduce the risks experienced by providing long term monitoring of subjects. This is a great idea whose time has come.

Monitoring participants during the trial for side effects and results is required in trials, but once the trial has ended, in most cases, all monitoring ceases.

Most trials start out looking at subjects with late stage disease, like chemotherapy for men with castrate resistant prostate cancer. As we find additional treatments that do extend life like abiriterone (Zytiga) and enzaludamide (Xtandi) and as we move these treatment protocols to earlier stage disease as has happened, researchers need to plan to monitor study participants for much longer follow-up periods. Frankly, this isn’t happening at an adequate level!

Increasingly, patients are surviving some cancers (like prostate cancer) for decades. Without adding prolonged follow-up for trial subjects any late toxicities and experiences are lost to medical science and the hero volunteers are literally left out to dry. Both the loss of the information as well as the potential cost of human suffering is inexcusable.

According to Jack Cuzick, PhD, FMedSci, FRCP(hon), head of the Centre for Cancer Prevention, director of the Wolfson Institute of Preventive Medicine, and John Snow Professor of Epidemiology at Queen Mary, University of London, in England, “Long-term follow-up of patients who participate in clinical cancer-prevention and cancer-treatment trials is an “important unmet need…..provision for some sort of long-term follow-up needs to be made at the outset of trials, and this should be a requirement for their approval,”1

“Ideally, all trial patients would be followed until death,” Dr. Cuzick said—though he is quick to acknowledge that follow-up durations will depend somewhat on the type of study in question.

Clifford Hudis, MD, chief of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center in New York, NY has said, “The length of duration should depend on the trial’s endpoints…what endpoints we use to measure outcomes depends on the setting. In the adjuvant and curative settings, you may have to worry about long-term toxicities and secondary primary cancers that can be a consequence of curative therapy, or secondary cancers like leukemia, or other illnesses such as cardiac disease.”

Dr. Cuzick cited a great example of why long-term follow-up is vital when he pointed out that there is an increase in myocardial infarction and cardiac death rates after radiotherapy for breast cancer, which only emerged after 10 years of follow-up. “Discovery of these late toxicities has led to a major change in radiotherapy planning and delivery, and the prospect from reduced cardiac toxicity and improved overall mortality using this modality is now high.”

Worrying about patient care for 3 or 5 or 6 years, for just for the duration of a trial, that’s very shortsighted. Long-term, life follow-up is very expensive and unless required it would be next to impossible to convince a for profit pharmaceutical company to perform . Clinical trials, as we currently conduct them are already very expensive; adding the additional costs of long-term follow-up care adds a major and sometimes impossible additional economic burden. Long-term care and follow-up would probably become a logistical nightmare. People move, they fail to respond to inquiries or they simply die.

Dr. Thompson has suggested that since, “A lot of cancer patients are in the Medicare system…if they allow you to do so, you can collect a huge amount of information passively at the only expense of paying Medicare for the data.” As an example he points to a study led by Dawn Hershman, MD, MS, at the Columbia University Medical Center in New York, NY in which late effects associated with androgen deprivation therapy in prostate cancer were assessed by linking patient trial data with corresponding Medicare claims.2

“You could do that with private insurers, too,” Dr. Thompson said. “It’s in their best interest, as well, as new therapies come along, to know the long-term impacts, because somebody’s going to be paying for those.”

 

References

  1. Cuzick J. Statistical controversies in clinical research: long term follow up of clinical trials in cancer
    [published online ahead of print October 3, 2015]. Ann Oncol. doi: 10.1093/annonc/mdv392.
  2. Hershman DL, Unger JM, Wright JD, et al. Long-term consequences of intermittent and continuous androgen deprivation in older patients with metastatic prostate cancer. J Clin Oncol. 2015;33(suppl): Abstract 5008.