Mike Hennessy

The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on not only clinical care but also research and development. Survey after survey predicts likely long-term implications for pharmaceutical research and development and specifically oncology clinical trials.

A survey by the American Society of Clinical Oncology (ASCO) of 32 investigators early in the COVID-19 pandemic found that institutions were delaying clinical research activities. Nearly 60% of respondents’ programs had halted screening and/or enrollment and ceased research-only visits except those providing cancer treatment. Additionally, 90.0% had implemented remote patient care, and 87.5% had implemented telehealth visits.

During the early part of the pandemic, more than half of programs reported prioritized enrollment, implementing various strategies to ensure adequate patients were in trials. These strategies included a tier-based approach based on patients’ needs, safety, and disease severity; potential patient and site burdens; and availability and allocation of program resources.

found 40% of institutions in the United States are still enrolling patients in oncology clinical trials, but half of those are doing so at a lower rate.

 Thirty-six US-based investigators interviewed for this survey said clinical research programs would not be fully operational for 3 to 6 months. Nearly 60% of investigators reported that COVID-19 had a moderate or high impact on delaying or canceling patient visits. Investigators acknowledged that this was a small survey, but that it indicates the effect that COVID-19 has had on cancer research. 

The survey included a separate analysis of IQVIA-run oncology clinical trials and found that milestone delays were the most common risk due to the pandemic. Additional analysis of data from ClinicalTrials.gov indicates that more than 200 interventional oncology studies were suspended in March and April 2020 because of COVID-19.

“We recognize the COVID-19 pandemic will have an enduring impact on the way oncology trials are conducted in the future,” Vanessa Hubbard-Lucey, PhD, MBA, director of the Cancer Research Institute’s Anna-Maria Kellen Clinical Accelerator and Venture Fund and coauthor of the 

paper, said in a press release. “Approaches such as digital patient recruitment, telemedicine, and remote monitoring can ensure patient safety and access to clinical trials [while] maintaining integrity of the trial and may be adopted with increasing frequency after this global crisis has resolved.”

According to the ASCO survey, challenges for continuing clinical trials during the COVID-19 pandemic included reluctance of patients to go for office visits and limited availability of services such as radiology and surgery. Respondents also said staff spent additional time organizing and implementing telehealth, as well as working with sponsors and independent review boards to modify trials.

Analysts at McKinsey & Company found sponsors worked hard to limit the disruptions to trials for oncology and rare diseases, whereas other areas such as gastrointestinal, infectious, and respiratory diseases and vaccines experienced significant disruption.

Research and development leaders said they are spending 40% to 50% of their time on crisis management, resulting in declines in productivity. 

These reports suggest clinical trials post COVID-19 will likely continue with many of the changes that have been implemented during the pandemic, all of which afford more focus on the patient and site. Limiting of in-person visits through telehealth and remote assessments could continue. Additionally, ASCO suggests that trials in the future could have expanded or flexible timelines and reduced data collection requirements, and e-signatures for trial documents should become standard practice.

1. Waterhouse D, Harvey RD, Hurley P, et al. Early impact of COVID-19 on the conduct of oncology clinical trials and long-term opportunities for transformation: findings from an American Society of Clinical Oncology survey. 

. 2020;16(7):417-421. doi:10.1200/OP.20.00275

2. Upadhaya S, Yu JX, Olivia C, Hooton M, Hodge J, Hubbard-Lucey VM. Impact of COVID-19 on oncology clinical trials. 

. 2020;19(6):376-377. doi:10.1038/d41573-020-00093-1

3. Cancer Research Institute and IQVIA uncover impact of COVID-19 pandemic on global oncology clinical trials. News release. Cancer Research Institute. May 18, 2020. Accessed July 6, 2020. bit.ly/2DiNHwh

4. Agrawal G, Parry B, Suresh B, Westra A. COVID-19 implications for life sciences R&D: recovery and the next normal. McKinsey & Co

May 13, 2020. Accessed July 6, 2020. mck.co/31Q7w84

Articles

ASCO: COVID-19 Will Have Long-Term Effects on Clinical Trials

With the fifth anniversary of the signing of the Affordable Care Act (ACA) into law upon us, ample time has passed to allow us to take stock of the law’s effects on the practice and business of cardiology, and to make some informed predictions regarding future developments.

At the recently concluded 2015 Annual Scientific Sessions of the American College of Cardiology, the co-editor-in-chief of 

 (also published by our company), Michael E. Chernew, PhD, professor of Healthcare Policy at Harvard Medical School, delivered a presentation on several ways in which the implementation of the ACA has changed the practice of cardiology. Chernew’s talk paid particular attention to the impact of new payment models and accountable care organizations (ACOs).

As noted in this summary of Chernew’s remarks (

), cardiologists “are affected by these changes more than most specialists, as a sizable share of their patients are older, sicker, and reliant on Medicare, which is demanding that physicians change the way they do business.” The most prominent change facing cardiologists and physicians in all specialties is the ongoing move from the traditional fee for service model to an approach that ties payment to value, bundling care across time and provider type.

One of the leading elements of this transition has been the emergence of ACOs, which are defined in the summary linked to above as “healthcare systems that take responsibility for patients at all levels of care, while giving those systems opportunities to share in savings if they produce better-than-expected health outcomes for their patient populations.” Chernew noted that although ACOs were designed to ensure coordination of care and slow spending growth (which he said has definitely happened for cardiologists), the organizations are not without their own challenges, including misaligned incentives, patients seeking care from more than one ACO (and also from non-ACO-affiliated providers), and complex payment benchmarks.

Chernew and another speaker in the session both reiterated that controlling costs in the era of bundled payments is going to come down to learning to better manage outpatient care, and that the shift from fee for service to payment for value is going to put more risk on providers. Local competition and increased consumerism that pushes patients to seek out and compare information on pricing and performance measures are going to drive the market.

Above all, cardiologists have to be proactive in embracing these changes, and get ahead of the curve by working for payment reform in their institutions, show they can contribute value and savings in areas like chronic disease management, and protecting (to the extent they can) extant fee-for-service revenue.

Another speaker underscored the importance of cardiologists becoming more involved in outpatient care, noting that this will represent a true change of mindset, because many practitioners have spent careers doing procedures that had little to do with outpatient care. This means that cardiologists will need to pay more attention to what happens after their patients leave the hospital (better coordination during transitions of care and more focus on where the patient is being discharged to).

We are living through a time of great upheaval and change in health care. Many old ways of doing business and thinking about patient care are going to fall by the wayside as newer approaches that prioritize quality of care and value of service are adopted.

With the fifth anniversary of the signing of the Affordable Care Act (ACA) into law upon us, ample time has passed to allow us to take stock of the law's effects on the practice and business of cardiology, and to make some informed predictions regarding future developments.

New Challenges, New Pressures in Cardiology

As of January 5, 2015, the Centers for Medicare & Medicaid Services (CMS) recognizes interventional cardiology as its own distinct physician specialty. The result of several years of lobbying by the Society for Cardiovascular Angiography and Interventions (SCAI), the new designation is a major achievement, according to the SCAI, because this recognition will enhance the ability of interventional cardiologists to represent their profession and their patients.

Several months ago, the SCAI offered additional details about why it was pursuing this goal. In an update to its members, the SCAI explained that interventional cardiology “has evolved to a point where many of the patients we treat and the treatments that we can offer are significantly different from those of general cardiology and other cardiovascular subspecialties. Having our own designation will help us to ensure that our concerns and priorities will receive sufficient consideration and will not be lumped in with those of others. This is especially important in today’s healthcare environment, when CMS and other payers are profiling providers based on the costs of the services they deliver to beneficiaries. SCAI expects that payers will soon be calculating the costs of procedures performed by interventional cardiologists and comparing those costs to those for treatments provided by noninvasive cardiologists, potentially leading to unfair, ‘apples-to-oranges’ comparisons of practice patterns and erroneous reporting of our members as outliers.”

The issue of unfair comparisons to outcomes achieved by other cardiologists and internists is at the heart of this effort, especially as those quality metrics are increasingly tied to reimbursement. SCAI secretary Peter Duffy, MD, told one news outlet that the move from a pay-for-volume environment to a pay-for-value system requires that interventional cardiologists be compared to one another in order to get a true picture of the value they bring.

The sicker, more complicated patients seen and treated by interventional cardiologists often have poorer outcomes that can impact quality-of-care performance scores. Advocates say the new designation allows these outcomes (and the level of resource utilization required to achieve them) to be seen and evaluated in the proper context.

Duffy has also noted that the new designation can benefit other noninterventional cardiologists as well, because now both specialists can be reimbursed for their work treating the same patient with less chance of having claims denied.

Achieving recognition as a separate and distinct specialty is an important milestone for interventional cardiology (as it was for cardiac electrophysiology several years ago). The question now is how this will play out against the changing reimbursement landscape, and whether other subspecialties within cardiology (heart failure-transplant cardiology?) will seek to follow the same path.

As of January 5, 2015, the Centers for Medicare & Medicaid Services recognizes interventional cardiology as its own distinct physician specialty. 

Separate Paths

, we present summaries of highly relevant studies in the areas of cardiology, pulmonology, gastroenterology, infectious disease, psychiatry, and neurology. Selected by our physician editor for their relevance to the practice of internal medicine, each study addresses a key clinical issue that can have a significant impact on patient care. Our writers have provided concise summaries of the key aspects and findings of each study, enabling readers to quickly ascertain the relevant facts. We have also provided links to the source materials to facilitate deeper reading.

In the “Cardiology” section of this issue, we highlight results from a study conducted by researchers at UT Southwestern Medical Center that indicate that cholesterol efflux may be a superior indicator of cardiovascular risk and a better target for therapeutic treatments than standard measurements of HDL. In their investigation of the relationship between HDL function and cardiovascular disease, the researchers reported finding “a strong, graded, protective relationship between cholesterol efflux and incidence of cardiovascular events among people who were free from heart disease at baseline testing.” These results are particularly interesting in light of recent studies showing little or no correlation between increases in HDL and reduction in cardiac events.

In the “Pulmonology” section this month, we highlight a study that looked at some of the evidence supporting the use of systemic corticosteroids in patients with COPD in the ICU. The authors reported that the optimal systemic corticosteroid formulation, dose, route of administration, and treatment duration are unclear, though there is some evidence suggesting that lower doses of corticosteroids in these patients may be associated with more favorable outcomes. The authors call for additional studies on this matter, but note that it could lead to substantial reductions in health care expenditures if further evidence should be found that supports the use of lower doses of corticosteroids.

Irritable bowel syndrome with diarrhea (IBS-D) is a frequently seen condition in the internal medicine setting. This condition can have a significant impact on patients’ quality of life, underscoring the importance of early diagnosis and treatment. In the “Gastroenterology’ section of 

 this month, we have included a study that looked at the effects of treatment with ondansetron vs. placebo in a group of patients diagnosed with IBS-D. In this crossover study, after 5 weeks of treatment, patients who received ondansetron reported significantly improved stool consistency, fewer days with urgency, less frequent defecation, and less bloating compared with their counterparts who received placebo.

With the flu season upon us, and amid reports that this year’s flu vaccine may not be as effective as previous year’s formulations, it is likely patients may ask about the use of over-the-counter treatments such as zanamivir and oseltamivir. A study in this month’s “Infectious Disease” section has some bad news for patients seeking relief from flu symptoms: neither of these treatments has much of effect. Study results showed that both reduced the time to symptomatic improvement by only about a half a day (and that performance may have been “attenuated by other symptom relief medication.” Clinicians and their patients should carefully weigh the trade-offs between potential harm and benefits when deciding whether to use these remedies.

Several studies have shown that medication management in conjunction with psychotherapy often produces the best outcomes in patients who have been diagnosed with major depressive disorder (MDD). A study in the “Psychiatry” section this month compared the effectiveness of treatment with cognitive behavioral therapy in combination with antidepressant medication to that of treatment with antidepressant medication alone in with chronic or recurrent MDD. Patients on combination therapy experienced improved recovery rates and fewer serious adverse events. Interestingly, the authors noted that this synergistic remedy will improve symptoms for only about one-third of patients because cognitive therapy engages different mechanisms than antidepressant medication, but likely only in some patients.

Finally, the “Neurology” section offers an interesting study in which investigators looked at patients with prefrontal lesions (PFL) and those with the behavioral variant of frontotemporal dementia (FTD) and compared their moral judgments to those of a control group by asking them to perform a task designed to disentangle the contributions of intentions and outcomes in moral judgment. Both groups of patients judged situations in which protagonists believed that they would cause harm but did not as being more permissible than the control group. According to the authors, this study appeared to be the first to directly compare a social cognition domain in 2 frontal pathologies with different etiologies. The study results highlighted the importance of comparing patients with vascular lesions and patients with neurodegenerative diseases.

Please read through these studies and let us know if your clinical experience confirms, contradicts, or differs from the conclusions reached by the investigators. As always, we are interested in your feedback as to how we can improve the content offered in 

. We are also looking for potential contributors and writers who want to share their knowledge and experience with their colleagues in internal medicine. Write to us at 

In this month's issue of Internal Medicine World Report (IMWR), we present summaries of highly relevant studies in the areas of cardiology, pulmonology, gastroenterology, infectious disease, psychiatry, and neurology. Selected by our physician editor for their relevance to the practice of internal medicine, each study addresses a key clinical issue that can have a significant impact on patient care.