Time to Treatment and the “Golden Hour”: Why They Matter and How Clinical Pathways Can Help

J Clin Pathways. 2024;10(4):21-28. doi:10.25270/jcp.2024.06.01

The importance of rapid access to high-quality health care is a well-established principle in medicine.¹ In the fields of trauma, neurology, and cardiovascu­lar medicine, the concept of the “golden hour” refers to the crucial time period immediately after a trauma, cerebrovascular injury, or myocardial infarction, when appropriate life-saving medical and/or surgical intervention can offer the highest chance of survival.^2-4

The principle of the golden hour has led to the development of evidence-based clinical pathways, national standards, accreditation processes, centers of excellence, policies, and procedures, and public awareness campaigns geared toward maximizing the potential for affected patients to receive expedited care that offers the greatest potential for long-term survival and quality of life.

There is a lack of compelling evidence that the time interval between cancer diag­nosis and treatment has a meaningful impact on the psychological status of patients newly diagnosed with cancer. One of the few related publications was an anony­mous online survey evaluating the psychological impact of prior authorization– related treatment delays among patients with cancer treated at Memorial Sloan Kettering Cancer Center in 2023. Among 178 subjects who completed the survey, 69% reported experiencing prior authorization–related care delays.⁵

Overall, 72% of respondents rated the prior authorization experience as either “bad” or “horrible” and self-reported pri­or authorization–related anxiety directly correlated with the length of delay. Prior authorization–related delays were also a significant source of mistrust of the very systems upon which patients relied for lifesaving care⁵:

• Eighteen percent of respondents reported “less trust in their cancer care team.”
• Eighty-three percent reported “less trust in the health care system.”
• Eighty-nine percent reported “less trust in their health insurer.”

Eighty percent of survey respondents were either Caucasian, college graduates, or privately insured, reflecting a cohort of patients with generally fewer barriers to care. While the higher socioeconomic status of this cohort might have influenced the depth of their psychological impact, it is also conceivable that the psychological impact of delayed cancer care could be even more profound for underserved patients who have historically faced significant barriers to timely health care.

Despite the lack of science regarding the psychological im­pact of cancer treatment delay, the last decade has witnessed a steady stream of medical literature that strongly establishes a causal relationship between delayed cancer care and worse overall survival. One of the first studies to reveal a connection between diagnosis-to-treatment interval and cancer survival evaluated the time interval from diagnostic needle biopsy to breast cancer surgery in 95 000 individuals with stage I-III in­vasive breast cancer included in the Surveillance, Epidemiol­ogy, and End Results (SEER)-Medicare program treated be­tween 1992-2009.⁶ Published in 2016, the analysis detected a 6%-13% reduction in 10-year overall survival for every ad­ditional 30-day delay-interval compared to those undergoing primary breast cancer surgery within 30 days of diagnosis.

Delay-related survival detriment was primarily observed in women with early stage (I and II) breast cancer, the cohort of women otherwise expected to have the most favorable survival prospects. In 2023, an updated analysis of the National Can­cer Database (NCDB) of patients treated between 2010-2014 found that a ≥ 9-week (63-day) interval between needle biopsy and surgical resection of breast cancer was significantly asso­ciated with a 15% relative reduction in 5-year overall survival compared to those completing breast cancer surgery within 30 days of diagnosis.⁷

Adverse impacts of treatment delay were even more pro­nounced in some subgroups. For example, women ≤ 45 years of age experienced a 32% relative reduction in 5-year overall survival when breast cancer surgery was delayed 31-60 days, which increased to a 64% relative reduction in 5-year overall survival when breast cancer surgery was delayed > 60 days. For patients with no insurance or Medicaid, 5-year survival was re­duced by 35% when breast cancer surgery was delayed 61-74 days or by more than two-fold when breast cancer surgery was delayed > 74 days. In evaluating these findings, it’s important to recognize that the NCDB compiles data from 1500+ hospitals that have been certified by the American College of Surgeons’ Commission on Cancer as delivering the highest level of cancer care in the US and encompasses approximately 70% of patients with breast cancer treated annually. The fact that such disparate treatment delays and survival outcomes are being realized at the highest quality cancer programs across the US is a call to action for broadly effective solutions to eliminate avoidable treatment delays in all demographic groups.

A growing body of evidence shows that delayed initiation of cancer care significantly increases the risk of death for multi­ple types of cancer. In a systematic review, Neal et al examined the survival implications of prolonged time to treatment ini­tiation (TTI) of symptomatic cancer.⁸ Although study size and study heterogeneity prevented definitive conclusions, shorter TTI was associated with more favorable survival outcomes for symptomatic breast cancer, colorectal cancer, head and neck cancer, testicular cancer, and melanoma.

In 2018, a multivariate analysis of the NCDB examined the relationship between TTI (ie, time to initial surgery, systemic therapy, or radiotherapy) and overall survival among 3.6 mil­lion patients treated between 2004-2013 for multiple types of non–distant metastatic cancer.⁹ Median TTI ranged from 21- 29 days. However, TTI > 42 days was associated with a sig­nificant reduction in 5-year overall survival for nearly all ma­jor cancer types, with the most substantial survival reductions seen in stage I non–small cell lung cancer (NSCLC) (HR, 1.032 [95% CI, 1.031-1.034]), stage I pancreatic cancer (HR, 1.030 [95% CI, 1.025-1.035]), stage I and II breast cancer (HR, 1.018 [95% CI, 1.015-1.020] and HR, 1.012 [95% CI, 1.010-1.015], respectively), and stage I and II renal cancer (HR, 1.013 [95% CI, 1.010-1.01] and HR, 1.012 [95% CI, 1.006-1.019]).

In 2020, Cone et al performed an updated analysis of the NCDB for the 4 most prevalent cancers in the US: non–meta­static breast cancer, prostate cancer, colon cancer, and NSCLC.¹⁰ Using TTI ≤ 60 days as the reference group, the study detected a statistically significant relative reduction in 5-year overall sur­vival for early-stage breast cancer, colon cancer, NSCLC, and high-risk prostate cancer. The median TTI ranged from 26-41 days for colon, breast, and lung cancer and 72 days for prostate cancer. However, TTI exceeding 60 days was documented in a significant proportion of patients with breast cancer (15%), colon cancer (10%), NSCLC (26%), and high-risk prostate can­cer (68.2%), conferring a greater risk of death due to cancer treatment delay.

The harmful effects of cancer treatment delay are not lim­ited to the interval between diagnosis and initial treatment. Studies examining the time intervals between initial therapy and adjuvant therapy revealed that delayed administration of adjuvant chemotherapy and/or radiotherapy can also sig­nificantly increase the risk of death. For example, a 2016 sys­tematic review by Hannah et al detected a 10%-15% relative reduction in overall survival for each 4-week interval that adjuvant systemic therapy or adjuvant radiotherapy was de­layed.¹¹ Among patients with breast cancer requiring surgery, adjuvant chemotherapy, and adjuvant radiotherapy, Pratt et al reported a 6.5% absolute reduction in 5-year cancer survival when the total span of treatment for all 3 modalities exceeded 38 weeks.¹²

Increasing complexity of the health care system and prior authorization requirements have contributed to steady rise in time to treatment over the past 2 decades. Khorana et al re­ported increased TTI from 21 to 29 days from 2004 to 2013. Although the 8-day increase might appear to be a modest de­lay, their analysis found that even a 7-day delay was associated with a 1.2%-3.2% increased relative risk of death, depending on the type of cancer.¹⁰ Factors associated with increased time to treatment included care within an academic center, transfer of care between facilities, Black race, multiple comorbid ities, lower education, older age, lack of insurance, or government-sponsored insurance.

Initially, one might question the clinical significance of a 10%-15% relative reduction in overall survival. However, to fully appreciate the magnitude of this survival reduction, it is helpful to compare it to the relative survival gains achieved with a typical course of adjuvant therapy for cancer. For example, for women with hormone receptor–positive stage I-II breast cancer, a 5-year course of antiestrogen therapy confers a 37% improvement (HR, 0.63 [95% CI, 0.56-0.71; P < .00001]) in relative 15-year overall survival, which can be significantly compromised by a > 60-day delay of initial sur­gery (HR, 1.15 [95% CI, 1.08-1.23; P < .001).7,13 The standard course of cisplatin-based adjuvant chemotherapy improved by 14% (HR, 0.86 [95% CI, 0.76- 0.98; P < .03]) the relative 5-year overall survival of resected stage I-II NSCLC, which can be completely negated by a > 6-week delay of primary surgery (HR, 1.17 [95% CI, 1.14-1.20; P < 0.05]).14,15 Similarly, fluo­rouracil-based adjuvant chemotherapy may offer an 18% im­provement (HR, 0.82 [95% CI, 0.70-0.95; P = .008]) in 5-year relative overall survival of stage II colon and rectal cancer, which can be completely undermined by a > 25-day delay of upfront surgery (HR, 1.24 [95% CI, 1.22-1.26; P < .001]).16,17 It is also plausible that common cancer treatment delays related to the deliberative process of clinical trial screening and enroll­ment might have masked real survival benefits of novel cancer therapies. The potential confounding influence of cancer treat­ment delay on clinical trial outcomes is sadly understudied and underscores the importance of recognizing and minimizing potential patient and researcher barriers to efficient clinical trial screening and enrollment in cancer clinical trials.

Considering the adverse impact of delayed TTI, it becomes readily apparent that TTI > 60 days can significantly dimin­ish or completely negate the survival gains that are sought from a variety of cancer treatments, which, from a patient perspective, may nonetheless be accompanied by significant treatment-related morbidity; adverse quality-of-life impact; and financial toxicity related to copays, deductibles, and lost in­come from work. Figures 1-3 summarize the relative improve­ment in overall survival conferred by several standard therapies compared to the relative reduction in overall survival caused by delay. From a health care economic perspective, excess health care dollars are spent attempting to achieve sometimes modest survival gains that have already been compromised by the de­lay leading up to therapy. For advanced disease, the economic burden is also reflected in the excessive cost of developing and administering novel systemic therapies, many of which have even less significant improvement on overall survival than the therapies for early-stage disease.^18,19

The argument for expanding the golden hour metaphor to oncology is to recognize the adverse survival, quality-of-life, and economic impacts of delayed cancer care and the need for policies, procedures, and technological solutions that promote timely access to high-quality cancer care. From a policy per­spective, efforts are already underway to establish time to treat­ment as a quality measure and to develop regulations and leg­islation that demand accountability from providers and payers to deliver timely cancer care. In 2022, the American Society of Breast Surgeons established TTI < 60 days for breast cancer treatment as a quality measure for its 3000+ members.²⁰ In a separate action the same year, the American College of Sur­geons’ Commission on Cancer established “time to therapeutic breast surgery < 60 days” as a new quality surveillance measure, impacting each of its 1500+ accredited sites.²¹ The Commission on Cancer is also expected to establish time-to-treatment stan­dards for other major cancer types.

Recognizing the role of prior authorization in cancer treatment delay, pending legislation²² aims to mandate expe­dited electronic prior authorization for all Medicare Advan­tage members, including approvals within 3 days for urgent authorizations and within 7 days for routine prior authoriza­tions. Medicare Advantage is the fastest-growing segment of the health care market. It is estimated to comprise 62% of the Medicare market by 2032.²³ If ultimately enacted, this legisla­tion will likely have far-reaching implications across the health care industry by raising the prior authorization requirements for all other segments of the health care insurance market.

Despite the recent emergence of policies, regulations, and legislation to promote timely cancer care, there are currently no widely utilized practices or technologies that are capable of reliably eliminating life-threatening delays in cancer care, es­pecially among marginalized populations. Furthermore, expe­dited care does not necessarily mean high-quality care, which means that an effective solution must not only eliminate cancer treatment delays but also make it easier for providers to offer cancer care that is concordant with national guidelines regard­less of insurance payer type or patient social determinants of health. That’s exactly how clinical pathways can help.

Clinical pathways are structured multidisciplinary care plans or clinical guidelines that link evidence to practice to optimize outcomes while maximizing clinical efficacy, minimizing un­desired practice variability and reducing health care costs. Cur­rently, the National Comprehensive Cancer Network (NCCN) has consensus guidelines for 68 different types of cancer that prescribe specific interventions as well as the optimal sequence of care.²⁴ However, NCCN guidelines are not very prescrip­tive about the timeline for completion of each intervention, which leaves many patients with cancer at significant risk of life-threatening cancer treatment delays.

Oncology clinical pathways can learn a lot from the clini­cal pathways guiding the management of acute myocardial in­farction, stroke, and trauma, each of which contains numerous time-to-intervention standards to which all accredited facilities are accountable for maintenance of certification. For example, acute chest pain guidelines established by the American Col­lege of Cardiology and the American Heart Association have 24 quality standards, of which 8 are time based, including the maximal number of minutes from a patient’s arrival to an emer­gency department to the performance and interpretation of an ECG (10 min) as well as the time from arrival to the emergen­cy department to initiation of fibrinolytic therapy (25 min).²⁵ Acute ischemic stroke guidelines from the American Health Association and the American Stroke Association consist of 17 quality standards, of which 8 are time based, including the time from arrival in the emergency department to initiating fibrinolytic therapy (≤ 60 min).²⁶ Similarly, international trau­ma guidelines include 82 quality indicators, of which 25 are time based, including the requirement for documenting “time to first medical contact” for all patients and, when applicable, “time to laparotomy” and “time to revascularization of a sev­ered limb.”²⁷ For each of the guidelines listed above, payers and accredited health care organizations have developed prearrival and postarrival policies, procedures, and workflows to ensure that time-based goals are met for all individuals, regardless of their level of insurance or personal circumstance. Health care organizations that fail to achieve these time-based goals are subject to loss of accreditation or loss of status as a dedicated treatment center, and payers that fail to facilitate such care are subject to fines or diminution of contracts.²⁸

To deliver timely and high-quality care, designers of oncol­ogy clinical pathways may utilize acute chest pain, stroke, and trauma guidelines as a model for establishing accountability for completing requisite, incremental time-based goals or standards that enable achievement of overall time-to-treatment bench­marks. Thus, the golden hour requires not only completing specific, guideline-supported interventions but also expeditious completion of intermediate or interval, rate-limiting interven­tions that cumulatively contribute to overall cancer treatment delay. For example, Neal et al outlined at least 15 essential, rate-limiting intervals that directly influence the overall time to treatment initiation.⁸ Although each interval is a potential source of delay, each is also a potential opportunity for time-based controls and greater accountability.

In oncology, the time from primary care referral to special­ist visit and the time from initial specialist visit to initial treat­ment are 2 treatment intervals that every patient must navi­gate. Both intervals generally require prior authorization and frequently necessitate clinical guideline–recommended imag­ing (eg, CT scan or MRI) or laboratory studies (eg, bloodwork or genetic testing) for optimal clinical decision-making and treatment planning. These additional ancillary studies might also require prior authorization. Oncology clinical pathways can effectively shorten overall TTI without compromising quality by prescribing optimal time frames for each interval (eg, time from primary referral to specialist visit < 7 days) while also holding the health plan and provider accountable for achieving this time-based goal. Only by setting incremen­tal goals and tracking compliance can a health care system be­gin to consistently meet time-to-treatment benchmarks for all patient demographics.

Digital health solutions are increasingly playing a central role in reducing cancer treatment delay. While many digital health so­lutions aim to expedite or automate prior authorization, none of the established prior authorization digital solutions (eg, Waystar, Myndshft, Rhyme, Infinitus, New Century Health, Carelon, EviCore) are specifically designed to maximize the potential for initiating cancer treatment within specific time­frames that are essential for improved cancer survival (ie, the golden hour). In fact, neither expedited nor automated prior authorization solutions are sufficient to eliminate provider edu­cation barriers (eg, non–guideline-supported orders), logistical barriers (eg, sequential rather than batch prior authorization), and scheduling bottlenecks that persist even when prior autho­rization delays are eliminated. Several clinical pathway solu­tions (eg, New Century Health, Carelon, EviCore, Epic Bea­con, Elsevier, McKesson) utilize decision support to minimize provider educational barriers but do little to overcome logisti­cal and scheduling barriers that interfere with the golden hour.

On the other hand, XpediteMD was specifically created to address each of the key structural barriers that delay initiation of cancer care (ie, provider educational, prior-authorization, logis­tical, and scheduling barriers). XpediteMD is a cloud-based, on­cology care management software platform designed for payers in collaboration with health care providers to streamline cancer care, eliminate treatment delays, close care gaps, and increase quality, while lowering the cost of care. The ability of Xpe­diteMD to reduce time to treatment was evaluated in an IRB quality-improvement initiative.²⁹ Five hundred and fifty-two consecutive participants with inconclusive or suspicious breast imaging designated as BI-RADS 0, 4, and 5 were enrolled and managed on the platform until a minimum of 50 participants were diagnosed and treated for breast cancer. Compared to a historical cohort where the average diagnosis to treatment in­terval was 74 days, the average interval for participants managed on the XpediteMD platform was only 17 days, a 77% reduc­tion in average time to treatment achieved in only 12 months. For the remaining 502 participants whose diagnostic work-up was negative, median time to completion of their noncancer workup (ie, a benign core biopsy finding or a decision to ob­tain follow-up imaging) averaged 22 days, which indicates that all evaluated participants benefitted from XpediteMD. Greater reductions in time to treatment might have been obtained had electronic medical record (EMR) integration been established between the parties during the quality-improvement initiative or had more specialists been enlisted to participate, thereby ex­panding the pool of potential appointments. Nonetheless, the Intermountain Healthcare Nevada quality-improvement initia­tive proves that comprehensive digital health solutions can con­sistently enable initiation of high-quality cancer care within the golden hour when appropriate life-saving interventions can offer the highest chance of survival.

Greater efficiency in the delivery of cancer care does not necessarily ensure lower cost of health care. For value-based care, the net balance of efficiency and quality must be reduced cost. By this measure, the Intermountain-XpediteMD qual­ity improvement initiative proved to be value based by not only enhancing efficiency and quality but also reducing payer administrative overhead by 80%, permitting one person to complete a series of tasks that previously required 4 people. Nonetheless, the quality improvement initiative greatly un­derestimated potential cost savings because of the payer’s deci­sion to forego accounting of all direct health care costs in the historical and study cohorts. For example, randomized con­trolled data show that treatment of patients utilizing a clini­cal pathway instead of non–pathway-guided care reduces the direct cost of cancer care by as much as 30%, in part due to cost avoidance from minimizing tests and procedures with minimal clinical benefit.^30,31 Furthermore, by automating or transition­ing some of the usual administrative processes from physicians to midlevel providers (eg, review of study results, initiation of new orders using decision support, patient communications), digital health solutions can reduce the labor cost of health care by allowing physicians, midlevel providers, and clinical staff to practice with maximal efficiency, while also improving pro­vider experience and reducing provider burnout.^32,33

Value-based care also requires understanding the relative cost impact of emerging digital health solutions, which can best be assessed with time-driven activity-based costing (TDABC). TDABC is an accounting method that is increasingly used in the health care setting to effectively understand clinical work­flows and resource utilization to enhance treatment efficiency, cost-effectiveness, and quality—the keystones of value-based care.³⁴ TDABC employs a bottom-up approach that determines the cost of each resource utilized in a workflow and the total length of time that the resource is in use. Informed by staff ob­servations and staff interviews, implementation of the TDABC analysis begins with creation of stepwise, time-specific process maps that outline the service in question based on an awareness of which individuals are involved in each step of the process and for how long each individual is involved. This approach permits estimation of personnel cost per minute by dividing each indi­vidual’s annual compensation by the number of minutes spent in performance of designated tasks. In this manner, the differen­tial cost rate of individuals in varying clinical roles (physicians, midlevels, and clinical support staff ) can be appropriately de­termined. In a similar fashion, per-minute depreciation-adjusted space and equipment costs are calculated from administrative data. After totaling the cost per minute of each personnel, the individual costs are multiplied by the hours worked and then combined with consumable costs to determine overall cost.

TDABC is well suited to quantify potential cost savings achieved by digital health solutions that enable each member of the health care team to function at the top of his or her license. This is accomplished by assigning to junior personnel work­ing in lower-cost workspaces (eg, remote locations) the kinds of tasks that need not be completed by more senior person­nel working in higher-cost workspaces. For example, digital clinical decision support solutions permit many tasks that are typically performed by primary care physicians (PCPs) to be reassigned to midlevel providers, each of whom can support multiple PCPs. These decision support–managed tasks may include review of normal and abnormal study results; submit­ting orders for imaging studies, biopsies, laboratory studies, and referrals; communicating results to patients as permitted by the PCP; and triaging or deferring to the PCP higher acuity clinical decisions and patient communications. By redirecting many of these tasks from PCPs, each PCP and his or her EMR inbox are relieved of the overwhelming burden of administra­tive tasks that frequently create data handling chokepoints that not only impede the timely initiation of cancer care but also increase the administrative cost of care.

The importance of rapid access to high-quality health care is a well-established principle in the fields of trauma, neurology, and cardiovascular medicine. These fields have embraced the golden hour metaphor in recognition of the relatively narrow time window immediately following a traumatic or vascular injury when appropriate life-saving medical and/or surgical intervention can have the greatest impact on morbidity, sur­vival, and economics, including patient financial toxicity. Given what we now understand about the frequency of cancer treat­ment delay and the magnitude of its impact on survival, there is strong rationale for expanding the golden hour definition to include cancer care. This would help develop diagnosis-specific policies, procedures, benchmarks, regulations, and enforcement mechanisms that promote timely initiation of high-quality cancer care. As we have seen in trauma and other specialties, clinical pathways are a perfect medium for not only facilitating evidence-based cancer care but also setting short-term, inter­val, time-driven goals that must first be met to achieve overall time-to-treatment goals.

Comprehensive digital health solutions like XpediteMD provide a useful strategy for streamlining and eliminating de­lays in cancer care, including the establishment and enforce­ment of time-driven interval benchmarks. Digital health solu­tions that set the golden hour as “true north” have the greatest potential to significantly reduce rising direct health care costs resulting from managing advanced cancers.³⁵ Reducing health care costs can also help to reduce rising patient financial tox­icity, which for cancer care alone in 2019 amounted to $21 billion, including $16 billion in out-of-pocket patient costs (eg, copays, coinsurance, and deductibles) and nearly $5 bil­lion in patient time costs (eg, travel time, wait times, and time receiving care).³⁶

Furthermore, by eliminating, reassigning, or automating many clinical and administrative processes, digital health solu­tions can significantly reduce indirect costs for health care fa­cilities and systems, health insurers, and health care providers. The impact of implementing digital health solutions is assessed using TDABC, which can reveal hidden costs and potential savings that can motivate frugal health care facilities and payers to enlist innovative digital health solutions to reduce cost and improve profit margins. Digital health solutions with embed­ded clinical pathways can provide an excellent vehicle for ex­panding value-based health care by simultaneously improving health care quality (eg, fewer deaths, less morbidity, and more guideline-compliant care); lowering direct and indirect health care costs; reducing patient financial toxicity; and achieving greater patient, provider, and payer satisfaction.

Authors: 

Dennis Holmes, MD^1,2; Juvairiya Pulicharam, MD²; Steven Evans, MD^3,4

Affiliations: 

¹Adventist Health Glendale, Glendale, CA; ²XpediteMD, Inc, Torrance, CA; ³SilverSummit Healthplan, Las Vegas, NV; ⁴Centene Corporation, St Louis, MO.

Address correspondence to: 

Dennis Holmes, MD

Adventist Health Glendale,

1505 Wilson Terrace,

Suite 370, Glendale, CA 91206

Email: dennis.holmes@xpeditemd.com

Disclosures: 

D.H. and J.P. reported being employees of and owning stock in XpediteMD, Inc. S.E. reported no relevant financial or other conflicts of interest.