Editorial

Cancer clinical trials: Not suitable for prime time

I am now very definitely within the demographic for those who watch prime-time TV.

The best indicator of this is, of course, not the programming, but the commercials. The level of advertising of new drugs seems to be increasing year after year — although I have no data to support that observation — and is clearly aimed at the baby boomer generation, covering new and not-so-new drugs for hyperlipidemia, chronic obstructive pulmonary disease, diabetes and various genitourinary problems.

The number of commercials for products related to cancer also seems to have increased quite dramatically. These had appeared to be limited to supportive care drugs, but there has been an increase in direct-to-patient advertising for anticancer drugs of various types over the last couple of years, with emphasis on improvements in DFS and, in some cases, OS. The commercials typically end with appropriate disclaimers — a rapid-fire description of possible toxicities and the parting advice to “talk to your doctor” about the product.

John Sweetenham

Not wishing to single out advertising for any specific product, I, like many, have concerns about direct-to-patient marketing of antineoplastic drugs.

Although the statements of potential benefit made in some of these commercials — including the survival benefit — often are technically true, they are given out of full context, and the magnitude of benefit is typically not stated clearly. So, at one level, the assertion that these commercials are “peddling hope” is justified, although viewers are being advised to talk to their doctors “to see if (drug name) is right for you.”

Trial accrual

A short but provocative viewpoint article in JAMA Oncology has altered my perspective on this. The opinion article by London and Kimmelman addresses references to clinical trials in cancer center advertising.

Before getting into the specifics of the article, it’s important to remember the context. Clinical trials have been the foundation of progress in oncology for decades. Well-conducted trials have defined and driven incremental improvements in cancer outcomes and translated groundbreaking laboratory research into sometimes paradigm-changing therapeutic advances. They are central to improving cancer outcomes for our patients.

Nationally, it is estimated that 2% to 3% of patients with cancer are placed on a therapeutic clinical trial. In academic oncology centers, that figure is typically higher, at anywhere from 10% to 20% at some of the highest-accruing centers. For major cancer centers, especially those designated by NCI, accrual to therapeutic trials is a major performance metric. Cancer centers invest substantial resources in the conduct of clinical trials to ensure patient safety, data integrity, regulatory compliance and timely conduct of clinical research, with the objective of making new therapies available to our patients as safely and as quickly as possible.

Trials are typically prioritized internally within cancer centers, where the highest priority is assigned to investigator-initiated trials, testing new agents or concepts developed within that center, followed by cooperative group trials and, then, industry-sponsored studies. Despite this well-intentioned prioritization to ensure that the highest-quality clinical research is given appropriate cancer center resources, many of those involved in clinical cancer research would probably acknowledge that the primary metric they follow is the number of therapeutic accruals, irrespective of the details of the specific trials.

Like many cancer centers, clinical trial accrual at my institution is a top priority and an ongoing challenge. Many centers, including ours, have seen a slight decline in trial accrual over the last couple of years. The causes for this are only partly understood but among them are the increasing cost and resources required to conduct clinical research, as well as the trend toward targeted agents. At our center, although we now screen and consent many more patients for studies, they frequently “screen out,” because their tumor does not express a specific marker or gene abnormality, making them ineligible — we get diminishing returns in terms of accrual for the increased efforts at screening.

Fortunately, we have been successful this year in reversing this trend in accrual and there is no doubt that we, like other large cancer centers, are quite appropriately expected to champion clinical trial participation. This is mainly driven by our mission, but also by our requirement to accrue patients to trials for continuation of funding.

One strategy used by many cancer centers for boosting trial accrual has been to increase awareness of clinical trials in our patient populations. This takes many forms, of which direct marketing to the public is one example. Advertising materials — ranging from print, to radio and TV advertising, as well as using social media platforms — are employed by many centers to promote their clinical trials. Although data on the effectiveness of this strategy to improve trial accrual are lacking, there is a widespread belief that the implied therapeutic advantage of trial participation may attract patients to a center with a large clinical research platform.

A lack of context

The question raised by the above-mentioned article is that of the use of implied therapeutic advantage in cancer center advertising of clinical trials.

The article cites many centers’ advertising implies that access to clinical trials provides patients with the chance to be among the first to benefit from new treatments. As the authors point out, this statement in itself undermines the clinical trials process, which is there to determine whether new treatments truly are beneficial. By sending an implied message that trial participation is intrinsically beneficial, we may be falsely raising our patients’ expectations.

Similarly, the authors note the tendency of cancer center advertising to link clinical trials with other new innovative technologies such as proton therapy, giving the impression that a group of advances, including clinical trials, provide a therapeutic edge. Of course, for many of our patients who participate in therapeutic trials, they really will be among the first to benefit from effective new therapies, but this needs to be placed in the context of many who will enter studies of “me too” drugs, which are not first in class, or may be placed on standard-of-care arms of prospective randomized trials. In the same way that drug advertising may provide false expectations of magnitude of benefit, advertising trials may do the same based on ineligibility or the lack of groundbreaking nature of many trials.

As the authors point out, some of these marketing approaches have the risk of threatening the underlying purpose of the clinical trials process which is so important to advancing cancer care and may also fuel support for the ‘right-to-try’ legislation, eloquently described by Derek Raghavan, MD, PhD, in his June 25 editorial for HemOnc Today.

Reflecting on this article, I have to conclude that some cancer center advertising may inadvertently be sending a similar message as the TV commercials for drugs — implied benefit without true context. To change this will require some new approaches to how we prioritize, fund and conduct clinical trials in cancer.

The good news is that innovative trial design, more rapid drug approval and an increasing number of effective, targeted therapies are likely to accelerate the access of our patients to game-changing treatments. The bad news is that clinical research remains extremely expensive and under-resourced from the perspective of central funding.

In an address at ASCO Annual Meeting, NCI Director Norman E. “Ned” Sharpless, MD, announced a substantial increase in basic scientific cancer research, with a comparatively tiny increase in funding available for clinical trials. Until the funding bodies are able to adequately prioritize and support high-quality clinical trials, most cancer centers are likely to continue to focus primarily on numbers of accruals — the use of direct marketing of trials to patients as a strategy for increased accrual is probably here to stay for now. But, maybe the message needs to be adjusted to dial down on the implied therapeutic edge and manage expectations — the risk is that we undermine the very process we are trying hard to support.

What works on prime time may not turn out to be the best approach for advancing our clinical trials agenda.

Reference:

London AJ and Kimmelman J. JAMA Oncol. 2018;doi:10.1001/jamaoncol.2018.0181.

For more information:

John Sweetenham, MD, FRCP, FACP, is HemOnc Today’s Chief Medical Editor for Hematology. He also is senior director of clinical affairs and executive medical director of Huntsman Cancer Institute at The University of Utah. He can be reached at john.sweetenham@hci.utah.edu.

Disclosure: Sweetenham reports no relevant financial disclosures.

I am now very definitely within the demographic for those who watch prime-time TV.

The best indicator of this is, of course, not the programming, but the commercials. The level of advertising of new drugs seems to be increasing year after year — although I have no data to support that observation — and is clearly aimed at the baby boomer generation, covering new and not-so-new drugs for hyperlipidemia, chronic obstructive pulmonary disease, diabetes and various genitourinary problems.

The number of commercials for products related to cancer also seems to have increased quite dramatically. These had appeared to be limited to supportive care drugs, but there has been an increase in direct-to-patient advertising for anticancer drugs of various types over the last couple of years, with emphasis on improvements in DFS and, in some cases, OS. The commercials typically end with appropriate disclaimers — a rapid-fire description of possible toxicities and the parting advice to “talk to your doctor” about the product.

John Sweetenham

Not wishing to single out advertising for any specific product, I, like many, have concerns about direct-to-patient marketing of antineoplastic drugs.

Although the statements of potential benefit made in some of these commercials — including the survival benefit — often are technically true, they are given out of full context, and the magnitude of benefit is typically not stated clearly. So, at one level, the assertion that these commercials are “peddling hope” is justified, although viewers are being advised to talk to their doctors “to see if (drug name) is right for you.”

Trial accrual

A short but provocative viewpoint article in JAMA Oncology has altered my perspective on this. The opinion article by London and Kimmelman addresses references to clinical trials in cancer center advertising.

Before getting into the specifics of the article, it’s important to remember the context. Clinical trials have been the foundation of progress in oncology for decades. Well-conducted trials have defined and driven incremental improvements in cancer outcomes and translated groundbreaking laboratory research into sometimes paradigm-changing therapeutic advances. They are central to improving cancer outcomes for our patients.

Nationally, it is estimated that 2% to 3% of patients with cancer are placed on a therapeutic clinical trial. In academic oncology centers, that figure is typically higher, at anywhere from 10% to 20% at some of the highest-accruing centers. For major cancer centers, especially those designated by NCI, accrual to therapeutic trials is a major performance metric. Cancer centers invest substantial resources in the conduct of clinical trials to ensure patient safety, data integrity, regulatory compliance and timely conduct of clinical research, with the objective of making new therapies available to our patients as safely and as quickly as possible.

PAGE BREAK

Trials are typically prioritized internally within cancer centers, where the highest priority is assigned to investigator-initiated trials, testing new agents or concepts developed within that center, followed by cooperative group trials and, then, industry-sponsored studies. Despite this well-intentioned prioritization to ensure that the highest-quality clinical research is given appropriate cancer center resources, many of those involved in clinical cancer research would probably acknowledge that the primary metric they follow is the number of therapeutic accruals, irrespective of the details of the specific trials.

Like many cancer centers, clinical trial accrual at my institution is a top priority and an ongoing challenge. Many centers, including ours, have seen a slight decline in trial accrual over the last couple of years. The causes for this are only partly understood but among them are the increasing cost and resources required to conduct clinical research, as well as the trend toward targeted agents. At our center, although we now screen and consent many more patients for studies, they frequently “screen out,” because their tumor does not express a specific marker or gene abnormality, making them ineligible — we get diminishing returns in terms of accrual for the increased efforts at screening.

Fortunately, we have been successful this year in reversing this trend in accrual and there is no doubt that we, like other large cancer centers, are quite appropriately expected to champion clinical trial participation. This is mainly driven by our mission, but also by our requirement to accrue patients to trials for continuation of funding.

One strategy used by many cancer centers for boosting trial accrual has been to increase awareness of clinical trials in our patient populations. This takes many forms, of which direct marketing to the public is one example. Advertising materials — ranging from print, to radio and TV advertising, as well as using social media platforms — are employed by many centers to promote their clinical trials. Although data on the effectiveness of this strategy to improve trial accrual are lacking, there is a widespread belief that the implied therapeutic advantage of trial participation may attract patients to a center with a large clinical research platform.

A lack of context

The question raised by the above-mentioned article is that of the use of implied therapeutic advantage in cancer center advertising of clinical trials.

The article cites many centers’ advertising implies that access to clinical trials provides patients with the chance to be among the first to benefit from new treatments. As the authors point out, this statement in itself undermines the clinical trials process, which is there to determine whether new treatments truly are beneficial. By sending an implied message that trial participation is intrinsically beneficial, we may be falsely raising our patients’ expectations.

PAGE BREAK

Similarly, the authors note the tendency of cancer center advertising to link clinical trials with other new innovative technologies such as proton therapy, giving the impression that a group of advances, including clinical trials, provide a therapeutic edge. Of course, for many of our patients who participate in therapeutic trials, they really will be among the first to benefit from effective new therapies, but this needs to be placed in the context of many who will enter studies of “me too” drugs, which are not first in class, or may be placed on standard-of-care arms of prospective randomized trials. In the same way that drug advertising may provide false expectations of magnitude of benefit, advertising trials may do the same based on ineligibility or the lack of groundbreaking nature of many trials.

As the authors point out, some of these marketing approaches have the risk of threatening the underlying purpose of the clinical trials process which is so important to advancing cancer care and may also fuel support for the ‘right-to-try’ legislation, eloquently described by Derek Raghavan, MD, PhD, in his June 25 editorial for HemOnc Today.

Reflecting on this article, I have to conclude that some cancer center advertising may inadvertently be sending a similar message as the TV commercials for drugs — implied benefit without true context. To change this will require some new approaches to how we prioritize, fund and conduct clinical trials in cancer.

The good news is that innovative trial design, more rapid drug approval and an increasing number of effective, targeted therapies are likely to accelerate the access of our patients to game-changing treatments. The bad news is that clinical research remains extremely expensive and under-resourced from the perspective of central funding.

In an address at ASCO Annual Meeting, NCI Director Norman E. “Ned” Sharpless, MD, announced a substantial increase in basic scientific cancer research, with a comparatively tiny increase in funding available for clinical trials. Until the funding bodies are able to adequately prioritize and support high-quality clinical trials, most cancer centers are likely to continue to focus primarily on numbers of accruals — the use of direct marketing of trials to patients as a strategy for increased accrual is probably here to stay for now. But, maybe the message needs to be adjusted to dial down on the implied therapeutic edge and manage expectations — the risk is that we undermine the very process we are trying hard to support.

What works on prime time may not turn out to be the best approach for advancing our clinical trials agenda.

Reference:

London AJ and Kimmelman J. JAMA Oncol. 2018;doi:10.1001/jamaoncol.2018.0181.

For more information:

John Sweetenham, MD, FRCP, FACP, is HemOnc Today’s Chief Medical Editor for Hematology. He also is senior director of clinical affairs and executive medical director of Huntsman Cancer Institute at The University of Utah. He can be reached at john.sweetenham@hci.utah.edu.

Disclosure: Sweetenham reports no relevant financial disclosures.