Mixed methods research offers powerful tools for investigating complex processes and systems in health and health care. This article describes integration principles and practices at three levels in mixed methods research and provides illustrative examples. Integration at the study design level occurs through three basic mixed method designs—exploratory sequential, explanatory sequential, and convergent—and through four advanced frameworks—multistage, intervention, case study, and participatory. Integration at the methods level occurs through four approaches. In connecting, one database links to the other through sampling. With building, one database informs the data collection approach of the other. When merging, the two databases are brought together for analysis. With embedding, data collection and analysis link at multiple points. Integration at the interpretation and reporting level occurs through narrative, data transformation, and joint display. The fit of integration describes the extent the qualitative and quantitative findings cohere. Understanding these principles and practices of integration can help health services researchers leverage the strengths of mixed methods.

/pdf/achieving-integration-in-mixed-methods-designs-principles-36zfo3ajv4.pdf

Achieving Integration in Mixed Methods Designs—Principles and Practices

Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations

Microtubules are highly dynamic structures, which consist of α- and β-tubulin heterodimers, and are involved in cell movement, intracellular trafficking and mitosis. In the context of cancer, the tubulin family of proteins is recognized as the target of the tubulin-binding chemotherapeutics, which suppress the dynamics of the mitotic spindle to cause mitotic arrest and cell death. Importantly, changes in microtubule stability and the expression of different tubulin isotypes as well as altered post-translational modifications have been reported for a range of cancers. These changes have been correlated with poor prognosis and chemotherapy resistance in solid and hematological cancers. However the mechanisms underlying these observations have remained poorly understood. Emerging evidence suggests that tubulins and microtubule-associated proteins may play a role in a range of cellular stress responses, thus conferring survival advantage to cancer cells. This review will focus on the importance of the microtubule-protein network in regulating critical cellular processes in response to stress. Understanding the role of microtubules in this context may offer novel therapeutic approaches for the treatment of cancer.

/pdf/microtubules-and-their-role-in-cellular-stress-in-cancer-15t0dezx14.pdf

Microtubules and Their Role in Cellular Stress in Cancer

Purpose The primary purposes of eligibility criteria are to protect the safety of trial participants and define the trial population. Excessive or overly restrictive eligibility criteria can slow trial accrual, jeopardize the generalizability of results, and limit understanding of the intervention's benefit-risk profile. Methods ASCO, Friends of Cancer Research, and the US Food and Drug Administration examined specific eligibility criteria (ie, brain metastases, minimum age, HIV infection, and organ dysfunction and prior and concurrent malignancies) to determine whether to modify definitions to extend trials to a broader population. Working groups developed consensus recommendations based on review of evidence, consideration of the patient population, and consultation with the research community. Results Patients with treated or clinically stable brain metastases should be routinely included in trials and only excluded if there is compelling rationale. In initial dose-finding trials, pediatric-specific cohorts should be included based on strong scientific rationale for benefit. Later phase trials in diseases that span adult and pediatric populations should include patients older than age 12 years. HIV-infected patients who are healthy and have low risk of AIDS-related outcomes should be included absent specific rationale for exclusion. Renal function criteria should enable liberal creatinine clearance, unless the investigational agent involves renal excretion. Patients with prior or concurrent malignancies should be included, especially when the risk of the malignancy interfering with either safety or efficacy endpoints is very low. Conclusion To maximize generalizability of results, trial enrollment criteria should strive for inclusiveness. Rationale for excluding patients should be clearly articulated and reflect expected toxicities associated with the therapy under investigation.

Broadening Eligibility Criteria to Make Clinical Trials More Representative: American Society of Clinical Oncology and Friends of Cancer Research Joint Research Statement

In 2011, health care spending in the United States was estimated at $27 trillion,1 making it the sixth largest economy in the world, larger than the national budget of France National health care spending is approximately 18% of the US gross domestic product, more than $8,000 per person, compared with 6% to 9% in Europe and elsewhere, with apparently similar patient outcomes Total Medicare expenditures in 2011 were $549 billion2 A study comparing the Canadian universal health care program in older patients with the Medicare program in the United States suggested that adopting more-prudent health care strategies could have saved $256 trillion from 1980 to 2009, or approximately one fifth of our national debt, without compromising benefit3

In the debate about health care and Medicare solvency, strategies that reduce health care costs without compromising treatment efficacy and patient safety should be explored Several experts have addressed health care costs in excellent analyses and editorials,4–9 but their efforts have not translated into concrete decisions and results that benefit patients, providers, insurers, or payees However, an interesting exception occurred recently when Bach et al,10 in a New York Times editorial, compared the efficacy and cost of two anticancer agents—ziv-aflibercept (Zaltrap; sanofi-aventis, Bridgewater, NJ) and bevacizumab (Avastin; Genentech, South San Francisco, CA)—in the treatment of metastatic colorectal cancer After noting ziv-aflibercept had similar efficacy but was twice the cost of bevacizumab, they stated it would be excluded from their hospital formulary10 Within 1 week, sanofi-aventis, the company producing ziv-aflibercept, reduced its price by 50% Thus, expert review of anticancer therapies for their cost-benefit ratios may influence institutional usage and drug pricing while preserving a healthy profit margin for pharmaceutical companies

Aristotle is credited to be the first to discuss the relationship between price and worth in his book Justum Pretium—the just price Sixteen centuries later, Saint Albert the Great and Saint Thomas Aquinas refined Aristotle's argument Their conclusion: of moral necessity, price must reflect worth In the context of cancer therapy, the prices of new anticancer agents seem to be decided by pharmaceutical companies according to what the market will bear There is little correlation between the actual efficacy of a new drug and its price, as measured by cost-efficacy (CE) ratios, prolongation of patient life in years, or quality-adjusted life-years (QALYs)7 Compared with a decade ago, the price range of new anticancer agents has more than doubled, from $4,500 to more than $10,000 per month4,5 Of the 12 anticancer drugs approved by the US Food and Drug Administration (FDA) in 2012, only three prolonged survival, two of them by less than 2 months Yet nine were priced at more than $10,000 per month Many so-called targeted therapies have been priced between $6,000 to 12,000 per month, or approximately $70,000 to 115,000 per patient annually (Table 1)11 However, novel or reformulated chemotherapy drugs like pralatrexate (Folotyn; Allos Therapeutics, Westminster, CO; $120,000 per course), omacetaxine (Synribo; Teva Pharmaceuticals, North Wales, PA; $28,000 for induction, $14,000 for monthly treatments), and pegylated asparaginase (Oncaspar; Sigma-Tau Pharmaceuticals, Gaithersburg, MD; $22,000 per course) are also expensive Hillner and Smith7 suggested that profiteering (ie, making profit by unethical methods, such as raising prices after natural disasters) could be applied to this recent trend, where a life-threatening disease is the natural disaster



Table 1

Cost of Targeted Therapy



Pharmaceutical companies justify the high price of drugs as necessary to support investment in research and development The often-cited cost of bringing anticancer drugs to FDA approval is $1 billion12 This figure is roughly calculated by dividing total expenditures on research and development by the number of agents that receive FDA approval However, this figure may be inflated, because it includes ancillary expenses, salaries, bonuses, and other indirect costs not related to research or development13 as well as an 11% compounded discount rate over 10 years based on stock market returns on capital investment14 Other independent estimates of cost of drug development put the figure as low as 4% to 25% of this estimate15–17

Allowing the producer-dominated market to set drug prices has spiraled the cost of cancer drugs out of control In this analysis, we highlight examples of the cost benefit of different anticancer agents and suggest scenarios for reduced drug pricing, while preserving the profit-making incentive, by linking price to a true measure of quality: preservation and meaningful prolongation of life

/pdf/cancer-drugs-in-the-united-states-justum-pretium-the-just-3op5kitsxy.pdf

Cancer Drugs in the United States: Justum Pretium—The Just Price

Targeting the molecular chaperone heat shock protein 90 (HSP90): lessons learned and future directions

Purpose of reviewContemporary oncology practice acknowledges the importance of partnering with the patient and family in dealing with the illness. Patients also value their physicians as important sources of support when they provide information about the illness, encouragement, and hope, discuss tr

Patient-physician communication in oncology: past, present, and future.

Distinguishing between grade II and grade III diffuse astrocytomas is important both for prognosis and for treatment decision-making. However, current methods for distinguishing between grades based on proliferative potential are suboptimal, making identification of clear cutoffs difficult. In this study, we compared the results from immunohistochemical staining for phospho-histone H3 (pHH3), a specific marker of cells undergoing mitosis, with standard mitotic counts (number of mitoses/10 high-power fields) and MIB-1 labeling index values for assessing proliferative activity. We tested the relationship between pHH3 staining and tumor grade and prognosis in a retrospective series of grade II and III infiltrating astrocytomas from a single institution. The pHH3 index (per 1000 cells), MIB-1 index (per 1000 cells), and number of mitoses per 10 high-power fields were determined for each of 103 cases of grade II and III diffuse astrocytomas from patients with clinical follow-up. pHH3 staining was found to be a simple and reliable method for identifying mitotic figures, allowing a true mitotic index to be determined. The pHH3 mitotic index was significantly associated both with the standard mitotic count and with the MIB-1 index. Univariate analyses revealed that all 3 measurements of proliferation were significantly associated with survival. However, the pHH3 mitotic index accounted for a larger proportion of variability in survival than standard mitotic count or MIB-1/Ki-67 labeling index. After adjusting for age, extent of resection, and performance score, the pHH3 mitotic index remained an independent predictor of survival. Thus, pHH3 staining provides a simple and reliable method for quantifying proliferative potential and for the stratification of patients with diffuse astrocytomas into typical grade II and III groups. These results also suggest that pHH3 staining may be a useful method in other neoplasms in which accurate determination of proliferation potential is relevant to tumor grading or clinical treatment decision-making.

Assessment and prognostic significance of mitotic index using the mitosis marker phospho-histone H3 in low and intermediate-grade infiltrating astrocytomas.

CASE HISTORY: PART 1 Oscar, a 9-year-old boy, was first diagnosed and treated for medulloblastoma at the age of 1 year. Eight years later, all anticancer treatment options for him had been exhausted. Although Oscar knew that he was dying, his parents could not accept the inevitable. Oscar’s parents would not allow anyone else to discuss the end of his life with himeither.Hereactedbybecomingdespondent and withdrawn and sometimes very obstinate.Hestoppedeating,washyperalert much of the time, and for the most part, would not talk.

https://ascopubs.org/doi/pdf/10.1200/JCO.2005.11.015

Silence is not golden: Communicating with children dying from cancer

Women with breast cancer have become increasingly more involved on a national and local level in advocating for resources to fight cancer. However, in the context of the relationship with their physicians and other cancer caregivers, much remains to be done in providing them with adequate support. In this paper, we highlight the difficulties in communication related to breast cancer and describe strategies and approaches that may be helpful in improving the communication throughout the cancer trajectory. Specifically, breast cancer patients have high unmet information needs relevant to health information and dissatisfaction with the actual information they receive from their providers. These needs seem even more pronounced when patients are older, of lower socio-economic class and from differing cultural backgrounds which may affect their ability to express their desires for information and desire to be involved in decision-making about their treatment. Other communication challenges can be envisioned as occurring at key points across the cancer trajectory: diagnosis disclosure, treatment failure, transition to palliative care, and end of life discussions. These involve techniques as basic as how to establish trust and rapport and determine a patient's information and decision-making preferences and as complex as giving bad news. These strategies are now viewed as essential skills in that they can affect patient distress and quality of life, satisfaction, and malpractice litigation as well as practitioner stress and burnout.

Joann Aaron

Papers

Targeting the molecular chaperone heat shock protein 90 (HSP90): lessons learned and future directions

Patient-physician communication in oncology: past, present, and future.

Assessment and prognostic significance of mitotic index using the mitosis marker phospho-histone H3 in low and intermediate-grade infiltrating astrocytomas.

Silence is not golden: Communicating with children dying from cancer

Breast cancer: unique communication challenges and strategies to address them.