key: cord-0910599-io3km4ru
authors: Saunders, Deanna; Liu, Michelle; Vandermeer, Lisa; Alzahrani, Mashari Jemaan; Hutton, Brian; Clemons, Mark
title: The Rethinking Clinical Trials (REaCT) Program. A Canadian-Led Pragmatic Trials Program: Strategies for Integrating Knowledge Users into Trial Design
date: 2021-10-04
journal: Curr Oncol
DOI: 10.3390/curroncol28050337
sha: 4182a811bb3e694ccf777829a5e309ff4b04dd43
doc_id: 910599
cord_uid: io3km4ru

We reviewed patient and health care provider (HCP) surveys performed through the REaCT program. The REaCT team has performed 15 patient surveys (2298 respondents) and 13 HCP surveys (1033 respondents) that have addressed a broad range of topics in breast cancer management. Over time, the proportion of surveys distributed by paper/regular mail has fallen, with electronic distribution now the norm. For the patient surveys, the median duration of the surveys was 3 months (IQR 2.5–7 months) and the median response rate was 84% (IQR 80–91.7%). For the HCP surveys, the median survey duration was 3 months (IQR 1.75–4 months), and the median response rate, where available, was 28% (IQR 21.2–49%). The survey data have so far led to: 10 systematic reviews, 6 peer-reviewed grant applications and 19 clinical trials. Knowledge users should be an essential component of clinical research. The REaCT program has integrated surveys as a standard step of their trials process. The COVID-19 pandemic and reduced face-to-face interactions with patients in the clinic as well as the continued importance of social media highlight the need for alternative means of distributing and responding to surveys.

There are many barriers to performing clinical trials and in recent years the number of adult cancer patients accrued to trials has steadily fallen [1] . The REthinking Clinical Trials (REaCT) Program was created with the intention of overcoming many of these barriers for comparing standard of care interventions, so that more patients could be offered participation in trials, participation would be less onerous, and results would be clinically important [2, 3] . While initially developed as an initiative in Ottawa, it became increasingly clear that investigators in other centres were also interested in participating in REaCT trials as well as leading their own studies using the REaCT infrastructure. Thus over the years the program has expanded to multiple sites across Canada. The key elements of the program are shown in Figure 1 , and broadly incorporate: identification of clinically relevant questions, conduct of systematic reviews of the evidence and surveys of end users, performance of pragmatic trials (using simply defined study endpoints, avoidance of superfluous data collection, use of an integrated consent model (ICM) incorporating oral consent [2, 4, 5] , efficient Research Ethics Board (REB) approval [6] , web-based randomisation in the clinic, and the use of real-time electronic data capture), economic analyses and knowledge mobilisation strategies. To date, the REaCT investigators have performed 20 randomized trials at 16 centres and has accrued over 3300 patients. The mandate of these trials has been broad, 

All surveys performed by the REaCT team since program inception in 2014 were reviewed as were studies performed by the team members that followed the same methodology. Where information was not available from the original publication of each survey, source documentation was sought if feasible.

Outcome data collected from patient surveys included patient demographics (i.e., type of cancer, stage of cancer), how potential survey participants were identified (e.g., from clinic lists), how participants were contacted for survey participation (e.g., approached by a HCP or cold-called by a study clinical research associate), how surveys were distributed to participants, and how survey responses were collected (in clinic, email, mail, various online platforms such as Microsoft Forms or the institution's electronic medical record EMR). Where possible, information on response rates to surveys was also collected.

Outcome data for HCP surveys included: types of participants (e.g., surgical/medical//radiation oncologists, surgeons, RNs, APNs), how participants were identified (e.g., society listings), how participants were contacted (email, various online platforms such as Microsoft Forms), how surveys were distributed, and how survey responses were collected (in clinic, email, Microsoft Forms). Using a modified Dillman approach, each survey was sent to HCPs at least twice [22] . Where possible, information on response rates to surveys was also collected.

The REaCT team members have performed and published 15 patient and 12 HCP surveys. These are outlined in Tables 1 and 2, respectively.

The surveys were consistently designed by a multidisciplinary team with demonstrated expertise in oncology, survey design, and methodology. Each survey was pilot tested on a limited number of patients, oncologists, advanced practice nurses and nonhealthcare professionals before launch. Over time, it has become clear that repeated readings of surveys are needed to ensure that they remain clearly written with unambiguous answers. In addition, keeping surveys as short as possible to ensure compliance is essential [23] .

As publication of survey results is the intent of most surveys performed, we used either local REBs or, where more than one site would be accrued, we used the Ontario Cancer Research Ethics Board (OCREB). In the few examples where there was no intent to publish, no REB approval was sought. This included ad hoc surveys of colleagues in our centre asking what differences in study outcomes would be enough to drive changes in practice for the purpose of sample size application for grants. In the current review we only discus those surveys with a formal protocol that follows the REaCT program processes.

A significant issue with surveys is ensuring that the response rate is high enough to make the study findings truly meaningful. Some authors have proposed that survey response rates should achieve at least 60% to ensure that the validity of results is not influenced by nonresponse bias [24] . There is literature on the use of incentives (e.g., financial reward for completing the survey) as a tool for increasing response rates [25] . However, as an academic investigator-led program such incentives could be financially prohibitive to actually performing the study. In addition, any honoraria received are also taxable income that should be declared by the recipient [25] . To date, we have only had funds to offer a gift voucher (a coffee card worth $5) to those physicians who sent us an email on completion of this REB-approved survey [26] . Led to a population-based cohort study [28] pre-and post-medication prophylaxis is required. A single protocol for post-medications is required when pre-medication not taken as prescribed.

Led to a clinic trial [55] 

Of the 15 patient surveys performed the survey topics addressed a broad range of topics including perceptions around post-operative radiological staging [27] , choices of adjuvant surgery/radiotherapy and endocrine therapy in patients ≥70 [29] , toxicities from endocrine therapy (hot flashes [32] , urogenital side effects [33] ), timing of starting endocrine therapy in patients receiving radiotherapy [78] , adjuvant chemotherapy choices of chemotherapy for TNBC [37] , ranking of chemotherapy toxicities for both early stage and metastatic patients [38, 49] , taxane-associated pain syndrome [50] , use of filgrastim for primary febrile neutropenia prophylaxis for adjuvant chemotherapy [51] , dosing of dexamethasone in patients receiving docetaxel [26] , choice of vascular access strategy for chemotherapy administration [56] , choice of endpoints for chemotherapy-induced nausea and vomiting (CINV) [58] and de-escalation of adjuvant bisphosphonates [59] . All of these surveys involved patients with breast cancer. Two surveys included patients with bone metastases, evaluating the use of bone-modifying agents (BMAs) accrued patients with breast cancer and castration resistant prostate cancer (CRPC) [61, 68] .

Of the 15 surveys performed, 5 required written consent. However, in more recent years, after working closely with local and provincial REBs all surveys used implied consent. Patients gave verbal consent to being approached for a survey and could choose to anonymously complete the survey or not. This occurred because of the increasing recognition that not all surveys required written consent and indeed the requirement for written consent could reduce the validity of study findings to reflect as broad a patient population as possible. Potential patients for surveys were often identified in the clinic (11/15), however in more recent surveys patients have also been identified and approached through their involvement in other studies [29, 32] and pharmacy lists [50, 68] . With the introduction of the MyChart function within the EPIC EMR patients are also now able to consent to being contacted about other studies [29, 32] . Previously while most studies would accrue patients through the physician at a clinic visit it is evident that more recent studies launched since March 2021 and COVID-19 restrictions on in-person visits to the clinic have used a combination of approaches including cold calling by study CRAs [29, 32, 68] . However, all eligible patients were approached and presented the survey by someone in their circle of care. Traditionally, REB approval has required that paper-based copies of any survey be available for all patients for completion either in the clinic or at home and this was so for all 15 studies. However, there has been an increasing move to responses being made by; telephone (3 surveys), email (9 surveys), use of a laptop in the clinic (2 surveys), or by regular mail (4 surveys). As responses to mailed out surveys have proven to be low we are no longer offering this option.

Using these strategies, a total of 2298 of 2624 contacted patients have responded to the 15 surveys. The median duration of the surveys was 3 months (IQR 2.5-7) and the median response rate was 84% (IQR 80-91.7%). The surveys frequently identified clinical equipoise (Table 1) , and all have been either published or are currently under review [29, 32] . The survey data led support to the REaCT program performing: a population-based cohort study (1), systematic reviews (10), peer-reviewed grant applications (6), review articles (3), treatment guidelines (4) and 19 clinical trials.

Of the 13 HCP surveys performed, the survey topics were similar to those in the patient surveys (Table 2 ).These topics included: development of a decision aid for breast cancer patients considering contralateral prophylactic mastectomy [73] , perceptions around post-operative radiological staging [74] , management of lobular cancer [75] , choices of adjuvant surgery/radiotherapy and endocrine therapy in patients aged 70 or over [77] , timing of starting endocrine therapy in patients receiving radiotherapy [78] , choice of chemotherapy for TNBC [37] , toxicities from endocrine therapy [81] , and supportive care studies for chemotherapy patients. These studies have evaluated: choice of vascular access for chemotherapy administration [83] , use of growth factors with neo/adjuvant chemotherapy for breast cancer [51] , dexamethasone pre-medication with docetaxel [26] , as well as the de-escalation of bone-modifying agents in both the adjuvant [84] and metastatic settings [85, 86] . Most studies related to the care of breast cancer patients, while the surveys evaluating bone-modifying agents in the metastatic setting [85, 86] also included patients with castration resistant prostate cancer.

A broad range of HCPs were surveyed including; medical oncologists (13) , radiation oncologists (9), surgical oncologists (7), oncology nurses (including advanced practice nurses (APNs) and nurse practitioners (NPs) (4), general practitioners in oncology (2) (2) . With time, these lists were used to derive a list of responsive HCPs that was used in 10 further surveys. All surveys included contacting HCPs by email and 2 also used regular mail. As these studies all received REB approval, they required a documented consent process. For the HCP surveys, completion of the survey (whether on paper or electronic) implied consent to participate in the study.

Using these strategies, a total of 1033 of 3280 contacted HCPs responded. For 13 surveys, the median duration of surveys was 3 months (IQR 1.75-4 months) and the median response rate, where available, was 28% (IQR 21.2-49%). Similar to the patient surveys, a consequence of the 13 HCP surveys was that they frequently identified clinical equipoise ( Table 2 ). All the surveys were published or are currently under review [77, 81] . The survey data led support to: a development of a decision aid, a population-based cohort study, 6 systematic reviews, 5 peer-reviewed grant applications, 2 review articles, 2 treatment guidelines and 15 clinical trials.

Surveys provide an important form of scientific inquiry that aim to gather reliable and unbiased data in an efficient, reasonably inexpensive, and adaptable way from a representative sample of respondents [23] [24] [25] . Knowledge user input through surveys is an essential part of the planning for any clinical trial. Knowledge users can provide invaluable information on such diverse issues as clinical equipoise, meaningful study endpoints, clinical importance of the question being asked, elements of study design to enhance pragmatism and improve enrollment, and willingness to participate in clinical trials (whether as a patient or as a treating physician). In this manuscript, we present the experience of the largest pragmatic oncology program that we are aware of in Canada. We also present important lessons learned regarding survey implementation thus far in the engagement of our most vital knowledge users. The lessons learned are particularly important in an era of rapid expansion of social media as well as the impact of the COVID-19 pandemic when face-to-face visits to the cancer centre are becoming less frequent and will likely remain so in the post-COVID world.

With 15 patient surveys that received feedback from 2298 respondents, and 13 HCP surveys answered by 1033 respondents covering a broad range of mainly breast cancerrelated topics, we feel we have successfully integrated surveys of knowledge users into our trials methodologies. The results of the current study show that planned collection and integration of knowledge user feedback in the Canadian health care system is feasible. These surveys have also provided information on clinical equipoise and endpoints that are important to patients. Indeed, an example was with our CINV patient survey where it was apparent that patients did not feel that the traditional endpoints used in emesis trials did not reflect the endpoints that were important to them [58] . This feedback led to a change in the design of our most recent study of CINV interventions, where nausea was made the primary endpoint [13] . Another example is the variability in filgrastim use in patients receiving chemotherapy for breast cancer [51] . This demonstration of clinical equipoise led to a successful clinical trial that showed shorter durations of filgrastim were equally effective as longer durations but with less toxicity [15] . Clearly it is therefore gratifying that our end user surveys have both directly and indirectly led to a number of important outcomes such as grant applications, systematic reviews, review papers and guidelines as well as actual clinical trials designed to answer the clinical equipoise that has been raised by end users.

Clearly as in all areas of research there are many potential limitations with performing surveys. With the need for a representative sample of respondents [23] [24] [25] , response rates are important. Indeed, journal reviewers frequently cite low response rates as a limitation, and can also represent a barrier to publication. A growing challenge is establishing what number represents an acceptable response rate nowadays as COVID-19 has fundamentally changed the nature of clinical care with a significant reduction in face-to-face interactions between HCPs and patients. With respect to patient surveys we have explored different strategies for enhancing both the approaching of patients (for example by using pharmacy lists, as well as the MYChart function on EPIC that allows patients to consent to be approached for research endeavours). There is also an inherent bias in the types of patients approached by HCPs as they are usually under the care of investigators involved in the particular study and also rarely reflect practice across nations as a whole. Our team has also faced low response rate to telephone and mail surveys, and increasingly we are trying to perform all surveys through electronic platforms. There is also the issue that implied consent as reflected through the completion of the survey may not actually mean that the subject fully understands the objective of the study. Finally, some journals have asked us to link certain survey responses to individual patient data [59] . As surveys are typically anonymous, such post hoc analyses are not possible. With respect to HCP surveys, a challenge has been relatively low response rates. For some membership listings (e.g., CANO), we were unable to target HCPs treating a specific tumour site, meaning that response rates are at times lowered as many recipients simply do not treat that type of cancer. There is also the inherent bias of the types of HCPs who respond which is difficult to overcome. While the use of financial incentives is outlined above, these costs put this type of initiative out of reach of many investigator-non-pharmaceutical company initiated studies [25] . Another important challenge is HCP irritability at receiving unsolicited emails for survey participation. We have tried to resolve this by asking HCPs to tell us if they are not interested in receiving these emails. Finally, there exists the limitation of the surveys thus far being predominantly breast cancer-related and having a Canadian bias.

We feel end user feedback will remain an essential component of any clinical research program. Future studies are clearly needed. These could evaluate better strategies for identifying and receiving responses from as broad a range of end users as possible. Such studies could also evaluate the use of social media platforms technology. For example, for our own patients in Ottawa harnessing convenience of EPIC electronic health records to do electronic surveys may present interesting ongoing opportunities). Future studies could also potentially allow expansion of the program outside of Canada.

Surveys of knowledge users are an essential component of clinical research. The REaCT program has integrated surveys as a standard step of their trials process which has resulted in; grant applications, systematic reviews, review papers, guidelines and clinical trials. The COVID-19 pandemic and reduced face-to-face interactions with patients in the clinic as well as the continued importance of social media highlight the need for alternative means of distributing and responding to surveys. 

The authors declare no conflict of interest.

Overcoming barriers to clinical trial enrollment

Novel Methodology for Comparing Standard-of-Care Interventions in Patients With Cancer

Creating a pragmatic trials program for breast cancer patients: Rethinking Clinical Trials (REaCT)

A multi-center pragmatic, randomized, feasibility trial comparing standard of care schedules of filgrastim administration for primary febrile neutropenia prophylaxis in early-stage breast cancer

Informed consent for pragmatic trials-the integrated consent model

Ethics and regulatory complexities for pragmatic clinical trials

A Randomized Controlled Trial Comparing Alloderm-RTU with DermACELL in Immediate Subpectoral Implant-Based Breast Reconstruction

Selecting patients for Oncotype DX testing using standard clinicopathologic information

An Integrated Consent Model Study to Compare Two Standard of Care Schedules for Monitoring Cardiac Function in Patients Receiving Trastuzumab for Early Stage Breast Cancer

A randomized trial comparing vascular access strategies for patients receiving chemotherapy with trastuzumab for early-stage breast cancer

A multicentre, randomized pilot trial comparing vascular access strategies for early stage breast cancer patients receiving non-trastuzumab containing chemotherapy

Risk model-guided antiemetic prophylaxis vs physician's choice in patients receiving chemotherapy for early-stage breast cancer: A randomized clinical trial

A randomized trial of individualized versus standard of care antiemetic therapy for breast cancer patients at high risk for chemotherapy-induced nausea and vomiting

Randomised feasibility trial to compare three standard of care chemotherapy regimens for early stage triple-negative breast cancer (REaCT-TNBC trial)

A multicentre, randomised trial comparing schedules of G-CSF (filgrastim) administration for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer

A randomised trial of 4-versus 12-weekly administration of bone-targeted agents in patients with bone metastases from breast or castration-resistant prostate cancer

Feasibility of using a pragmatic trials model to compare two primary febrile neutropenia prophylaxis regimens (ciprofloxacin versus G-CSF) in patients receiving docetaxel-cyclophosphamide chemotherapy for breast cancer (REaCT-TC)

Feasibility outcomes of a randomised, multicentre, pilot trial comparing standard 6-monthly dosing of adjuvant zoledronate with a single one-time dose in patients with early stage breast cancer

A Guide to Researcher and Knowledge-User Collaboration in Health Research

Perspectives on involvement in the peer-review process: Surveys of patient and public reviewers at two journals

The COVID-19 pandemic: An opportunity to rethink and harmonise the frequency of follow-up visits for patients with early stage breast cancer

The design and administration of mail surveys

Surviving Surveys

Why are response rates in clinician surveys declining?

Third-party online surveys-Science, selling, or sugging?

Optimisation of steroid prophylaxis schedules in breast cancer patients receiving docetaxel chemotherapy-A survey of health care providers and patients

Patient perceptions and expectations regarding imaging for metastatic disease in early stage breast cancer

Imaging for distant metastases in women with early-stage breast cancer: A population-based cohort study

Experiences and perceptions of older adults with lower-risk hormone receptor-positive breast cancer about adjuvant radiotherapy and endocrine therapy: A patient survey

De-escalating adjuvant therapies in older patients with lower risk estrogen receptor-positive breast cancer treated with breast-conserving surgery: A systematic review and meta-analysis

Evaluating Harms and Benefits of Endocrine Therapy in Patients ≥70 Years of Age with Lower Risk Breast Cancer

Developing patient-centered strategies to optimize the management of vasomotor symptoms in breast cancer patients: A patient survey. Breast Cancer In press

Prevalence and severity of urogenital symptoms in postmenopausal women receiving endocrine therapy for breast cancer

Should urogenital atrophy in breast cancer survivors be treated with topical estrogens?

Management of urogenital atrophy in breast cancer patients: A systematic review of available evidence from randomized trials

Are Estring ® and Vagifem ® equally effective and safe for the treatment of urogenital atrophy in breast cancer patients on aromatase inhibitor therapy?

Enhancing accrual to chemotherapy trials for patients with early stage triple-negative breast cancer: A survey of physicians and patients

Use of conjoint analysis to assess breast cancer patient preferences for chemotherapy side effects

A systematic review of the incidence and risk factors for taxane acute pain syndrome in patients receiving taxane-based chemotherapy for prostate cancer

Taxane acute pain syndrome (TAPS) in patients receiving taxane-based chemotherapy for breast cancer-A systematic review

Treatment of taxane acute pain syndrome (TAPS) in cancer patients receiving taxane-based chemotherapy-A systematic review

Identifying an optimal antiemetic regimen for patients receiving anthracycline and cyclophosphamide-based chemotherapy for breast cancer-an inspection of the evidence base informing clinical decision-making

The development of a prediction tool to identify cancer patients at high risk for chemotherapy-induced nausea and vomiting

Choice of study endpoint significantly impacts the results of breast cancer trials evaluating chemotherapy-induced nausea and vomiting

A prospective multi-centre, randomized study comparing the addition of tapering dexamethasone to other standard of care therapies for taxane-associated pain syndrome (TAPS) in breast cancer patients

A cost-utility analysis of risk model-guided versus physician's choice antiemetic prophylaxis in patients receiving chemotherapy for early-stage breast cancer: A net benefit regression approach

Taxane acute pain syndrome (TAPS) in patients receiving chemotherapy for breast or prostate cancer: A prospective multi-center study

Clinical utility of a prediction tool to differentiate between breast cancer patients at high or low risk of chemotherapy induced nausea and vomiting

Preference weights for chemotherapy side effects from the perspective of women with breast cancer

Incidence of taxaneinduced pain and distress in patients receiving chemotherapy for early-stage breast cancer: A retrospective, outcomes-based survey

Filgrastim use in patients receiving chemotherapy for early-stage breast cancer-A survey of physicians and patients

Primary febrile neutropenia prophylaxis for patients who receive FEC-D chemotherapy for breast cancer: A systematic review

Optimal primary febrile neutropenia prophylaxis for patients receiving docetaxel-cyclophosphamide chemotherapy for breast cancer: A systematic review

A multi-centre study comparing granulocyte-colony stimulating factors to antibiotics for primary prophylaxis of docetaxelcyclophosphamide induced febrile neutropenia

A randomized clinical trial comparing physician-directed or fixed-dose steroid replacement strategies for incomplete dexamethasone dosing prior to docetaxel chemotherapy

Perceptions of vascular access for intravenous systemic therapy and risk factors for lymphedema in early-stage breast cancer-A patient survey

Optimal vascular access strategies for patients receiving chemotherapy for early-stage breast cancer: A systematic review

Defining optimal control of chemotherapy-induced nausea and vomiting-Based on patients' experience

Adjuvant bisphosphonate use in patients with early stage breast cancer: Patient perspectives on treatment acceptability and potential de-escalation

Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: A Cancer Care Ontario and American Society of Clinical Oncology Clinical Practice Guideline

Bone-targeted agent use for bone metastases from breast cancer and prostate cancer: A patient survey

De-escalation of bone-modifying agents in patients with bone metastases from breast cancer: A systematic review and meta-analysis

Should de-escalation of bone-targeting agents be standard of care for patients with bone metastases from breast cancer? A systematic review and meta-analysis

Practical Update for the Use of Bone-Targeted Agents in Patients with Bone Metastases from Metastatic Breast Cancer or Castration-Resistant Prostate Cancer

De-escalation of bone-targeted agents for metastatic prostate cancer

Effects on bone resorption markers of continuing pamidronate or switching to zoledronic acid in patients with high risk bone metastases from breast cancer

Effects of de-escalated bisphosphonate therapy on bone turnover biomarkers in breast cancer patients with bone metastases

Perceptions around bone-modifying agent use in patients with bone metastases from breast and castration resistant prostate cancer: A patient survey

Long-term benefits versus side-effects from bone-targeted therapies for cancer patients: Minimizing risk while maximizing benefits

Long-term impact of bone-modifying agents for the treatment of bone metastases: A systematic review

A randomized, double-blind, phase II, exploratory trial evaluating the palliative benefit of either continuing pamidronate or switching to zoledronic acid in patients with high-risk bone metastases from breast cancer

A Randomised Trial Comparing Continuation or De-escalation of Bone Modifying Agents (BMA) in Patients Treated for Over 2 Years for Bone Metastases From Either Breast or Castration-Resistant Prostate Cancer (REaCT-Hold BMA)

Patient decision aid for contralateral prophylactic mastectomy for use in the consultation: A feasibility study

Imaging for metastatic disease in patients with newly diagnosed breast cancer: Are doctor's perceptions in keeping with the guidelines?

Treatment choices for patients with invasive lobular breast cancer: A doctor survey

Invasive pleomorphic lobular carcinoma of the breast: Pathologic, clinical, and therapeutic considerations

Management strategies for older patients with low-risk early stage breast cancer: A physician survey

Physician Survey of Timing of Adjuvant Endocrine Therapy Relative to Radiotherapy in Early Stage Breast Cancer Patients

Optimal sequence of adjuvant endocrine and radiation therapy in early-stage breast cancer-A systematic review

Evaluating Optimal Timing of Endocrine Therapy and Radiation Therapy in Early-Stage Breast Cancer (REaCT-RETT)

Developing patient-centered strategies to optimize the management of vasomotor symptoms in breast cancer patients: A survey of health care providers

Comparing Interventions for Management of Hot Flashes in Patients With Breast and Prostate Cancer: A Systematic Review With Meta-Analyses

Optimizing vascular access for patients receiving intravenous systemic therapy for early-stage breast cancer-A survey of oncology nurses and physicians

Adjuvant bisphosphonate use in patients with early stage breast cancer: A physician survey

De-escalated administration of bone-targeted agents in patients with breast and prostate cancer-A survey of Canadian oncologists

Real-world practice patterns and attitudes towards de-escalation of bone-modifying agents in patients with bone metastases from breast and prostate cancer: A physician survey

Two-year results of a randomised trial comparing 4-versus 12-weekly bone-targeted agent use in patients with bone metastases from breast or castration-resistant prostate cancer

Oral magnesium supplements for cancer treatment-induced hypomagnesmia: Results from a pilot randomized trial