Implementation Research Takes On an Increasingly Essential Role in Oncology

Maurie Markman, MD

Clinical trials play a central role in oncology. The existence of solid, evidence-based disease management would not be possible without well-designed and well-conducted studies.

However, the publication of the objectively meaningful outcomes of such efforts in high-impact peer-reviewed medical journals does not necessarily result in the observations being implemented into routine clinical care. Several reasons may explain the substantial delays noted between the publication of highly relevant data and uptake of the results into practice.

Reasons include the following:

• The results alter well-established, widely accepted approaches to disease treatment.
• Changes may lead to potentially complex, unproductive, and expensive training for clinicians and staff.
• Changes may add time to a routine clinical encounter without adding remuneration.
• There may be a lack of local resources or supportive personnel to implement a new practice.
• Implementation may negatively affect personal and practice finances.

Conversely, if essential training is provided by a source outside the practice on the evidence-based treatment approach, effectively marketed clinical trial results that suggest a new approach to disease management may lead to a greater willingness to carefully evaluate and subsequently employ the tactic. Further, if such implementation is associated with a favorable financial return, a practice will almost certainly show more interest.

If a new anticancer agent demonstrates meaningful activity for new clinical indications in initial registration trials or in subsequent studies leading to regulatory approval, a drug manufacturer may be willing to spend considerable time (and money) to inform oncologists of this development. This may include providing assistance in obtaining third-party insurance coverage for individual patients or any required training related to drug administration and safety.

However, the situation is likely to be quite different if the trial is not associated with a sponsor or any other form of support necessary to optimize meaningful implementation. In the opinion of this commentator, an increasing number of critically relevant observations and important study results published in peer-reviewed medical and oncology literature stagnate because there is no implementation plan or subsequent effort at encouraging clinical uptake.

Investigators of such projects may win awards for the quality of their research, subsequently obtain precious peer-reviewed grant funding, achieve promotion at their institution or elsewhere, or be awarded membership in prestigious national organizations, but their research findings themselves sometimes go nowhere. To be clear, there is no suggestion that this was ever the investigator’s intent, but it may be the result of the absence of an effective implementation plan.

There is a critical need in the oncology community for meaningful, focused efforts in implementation research. Consider the following: A recent study looked at adherence to established guidelines for venous thromboembolism prophylaxis following pancreatic surgery. The study’s results revealed that among 888 patients deemed eligible to receive such therapy upon hospital discharge, only 3.8% (34 individuals) “filled a prescription for venous thrombotic prophylaxis within 5 days of hospital discharge.”¹ This is rather concerning considering that data from both clinical guidelines and trials support the use of such prophylaxis after major surgery involving the abdominal cavity.^2,3

How might surgeons be encouraged to use and inform patients of a known effective and safe measure to reduce the risk of this serious surgery complication?

A second example within the realm of cancer surgery suggests the need to understand and positively affect findings from thoracic oncology studies. A specific example is a retrospective cohort analysis of individuals with stage IB to IIIA non–small cell lung cancer (NSCLC) in the ALCHEMIST Screening Trial (NCT02194738) who did not subsequently participate in an adjuvant therapy trial and who had a cancer measuring at least 4 cm in diameter, with or without positive lymph nodes.⁴

Among 2833 patients (53% women), 95% were underwent surgical resection, but only 53% were found to have had “adequate lymph node dissection.”⁴ A similarly low percentage of individuals (57%) received any adjuvant therapy, with only 44% receiving a minimum of 4 cycles of platinum-based chemotherapy, despite solid evidence revealing the value of such treatment. Although the authors of this provocative and concerning analysis appropriately conclude that “efforts are needed to optimize the use of proven therapies for early-stage NSCLC”⁴ the question is how do we effectively implement efforts to change what for many oncologists appears to be current routine surgical practice?⁴

It is not difficult to find documented evidence outside the realm of surgical oncology that challenges the oncology community to focus research on strategies to more effectively improve outcomes or enhance patients’ quality of life. Topics highlighted in recent publications include disparities in electronic screening for cancer-related psychosocial distress⁵ and inadequacies in performance guideline–recommended geriatric assessments.⁶

In the opinion of this commentator, there must be a more prominent role in our community’s investigative agenda for implementation research designed to discover and activate strategies to encourage widespread use of new, effective approaches to cancer management.

References

1. Perry LM, Bateni SB, Merkow RP, et al. Evaluation of adherence to venous thromboembolism prophylaxis guidelines among US adults after pancreatic cancer surgery. JAMA Surg. Published online July 13, 2022. doi:10.1001/jamasurg.2022.2590
2. Felder S, Rasmussen MS, King, et al. Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery. Cochrane Database Syst Rev. 2019;11(11):CD004318. doi:10:1002/14651858.CD004318.pub3
3. Vedovati MC, Becattini C, Rondelli F, et al. A randomized study on 1-week versus 4-week prophylaxis for venous thromboembolism after laparoscopic surgery for colorectal cancer. Ann Surg. 2014;259(4):665-669. doi:10.1097/SLA.0000000000000340
4. Kehl K, Zahrieh D, Yang P, et al. Rates of guideline-concordant surgery and adjuvant chemotherapy among patients with early-stage lung cancer in the US ALCHEMIST Study (Alliance A151216). JAMA Oncol. 2022;8(5):717-728. doi:10.1001/jamaoncol.2022.0039
5. Sutton TL, Koprowski MA, Gold JA, et al. Disparities in electronic screening for cancer-related psychological distress may promote systemic barriers to quality oncologic care. J Natl Compr Canc Netw. 2022; 20(7):765-773.e4. doi:10.6004/jnccn.2022.7015
6. Dale W. Why is geriatric assessment so infrequently used in oncology practices? The ongoing issue of nonadherence to this standard of care for older adults with cancer. JCO Oncol Pract. 2022;18(7)475-477. doi:10.1200/OP.22.00197