Guidelines For Management Of Cancer Research Articles

Guideline for the Initial Management of Small Cell Lung Cancer (Limited and Extensive Stage) and the Role of Thoracic Radiotherapy and First-line Chemotherapy

AimsWe investigated the efficacy of adding radiotherapy to chemotherapy in patients with extensive stage small cell lung cancer (ES-SCLC) and the appropriate timing, dose and schedule of treatment for patients with ES-SCLC or limited stage SCLC (LS-SCLC). Materials and methodsThe guideline was developed by Cancer Care Ontario's Program in Evidence-Based Care and by the Lung Cancer Disease Site Group through a systematic review of randomised controlled trials. Key recommendationsIn patients with LS-SCLC (stage I, II and III), the addition of thoracic radiotherapy to standard chemotherapy is recommended. However, there is no clear evidence to inform definitive recommendations for optimal timing, sequential versus concurrent therapies and optimal dose or regimen. In patients with LS-SCLC, etoposide–cisplatin is the preferred regimen for adults who are being treated with combined modality therapy with curative intent. In patients with ES-SCLC (stage IV), there is insufficient evidence to recommend the addition of thoracic radiotherapy to standard chemotherapy as a standard practice for survival benefit; however, it could be considered on a case-by-case basis to reduce local recurrence. In patients with ES-SCLC, a platinum agent plus etoposide is the preferred regimen for adult patients who are being treated with combined modality therapy. Cisplatin and irinotecan represents an alternative treatment option to this, but is associated with increased rates of adverse events such as diarrhoea.

Practice guidelines for management of ovarian cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement.

Since after 2006 when the first edition of practice guidelines for gynecologic oncologic cancer treatment was released, the Korean Society of Gynecologic Oncology (KSGO) has published the following editions on a regular basis to suggest the best possible standard care considering updated scientific evidence as well as medical environment including insurance coverage. The Guidelines Revision Committee was summoned to revise the second edition of KSGO practice guidelines, which was published in July 2010, and develop the third edition. The current guidelines cover strategies for diagnosis and treatment of primary and recurrent ovarian cancer. In this edition, we introduced an advanced format based on evidence-based medicine, collecting up-to-date data mainly from MEDLINE, EMBASE, and Cochrane Library CENTRAL, and conducting a meta-analysis with systematic review. Eight key questions were raised by the committee members. For every key question, recommendations were developed by the consensus meetings and provided with evidence level and strength of the recommendation.

Do we need regional guidelines for breast cancer management in the MENA region? MENA Breast Cancer Guidelines project.

PurposeBreast cancer is the most common cancer among females worldwide in general and in the Middle East and the North African region (MENA region) in particular. Management of breast cancer in the MENA region faces a lot of challenges, which include younger age at presentation, aggressive behaviour, lack of national breast screening programmes and lack of reliable data registries as well as socioeconomic factors. These factors make applying the international guidelines for breast cancer management very challenging. The aim of this project is to explore the need for a regional breast cancer guideline as well as to screen the clinical practice of breast cancer management in the MENA region.MethodologyThree web-based designed surveys were sent to more than 600 oncologists in the MENA region from the period of August 2013 to October 2014. Full descriptive data and information regarding the application of international breast cancer guidelines were collected. The software was using the IP address to prevent duplication of collected data. Descriptive analysis and results were shown as numbers and percentages.ResultsDuring the period of the survey, 104 oncologists responded, representing around an 11% response rate. The majority of replies came from Egypt (59 responses (59%)), followed by Saudi Arabia (ten responses (9.6%)). Fifty-one per cent of responders had more than ten years of experience, and further 31.7% had 5–10 years of experience. Seventy-four per cent were working in governmental hospitals, which is our target sector. There was a major defect in having a genetic counsel unit (78.8% declared an absence of this service), presence of a national breast screening programme (55.8% declared an absence of this service), performing sentinel lymph node biopsy (43.3% declared an absence of this service). The need for regional guidelines for the management of breast cancer was agreed upon by 90.6% of responders.ConclusionThere is a clear need to improve the management of breast cancer in the MENA region. Creating a national breast screening programme and a reliable database is essential. A regional guideline is required to establish the best possible management of breast cancer according to the patients and disease specification as well as the regional socioeconomic factors and facilities available. There is also a need to improve clinical research that meets the region’s needs.

Risks of CIN 2+, CIN 3+, and Cancer by Cytology and Human Papillomavirus Status: The Foundation of Risk-Based Cervical Screening Guidelines.

The next round of the American Society for Colposcopy and Cervical Pathology (ASCCP)-sponsored cervical cancer screening and management guidelines will recommend clinical actions based on risk, rather than test-based algorithms. This article gives preliminary risk estimates for the screening setting, showing combinations of the 2 most important predictors, human papillomavirus (HPV) status and cytology result. Among 1,262,713 women aged 25 to 77 years co-tested with HC2 (Qiagen) and cytology at Kaiser Permanente Northern California, we estimated 0-5-year cumulative risk of cervical intraepithelial neoplasia (CIN) 2+, CIN 3+, and cancer for combinations of cytology (negative for intraepithelial lesion or malignancy [NILM], atypical squamous cells of undetermined significance [ASC-US], low-grade squamous intraepithelial lesion [LSIL], atypical squamous cells cannot exclude HSIL [ASC-H], high-grade squamous intraepithelial lesion [HSIL], atypical glandular cells [AGC]) and HPV status. Ninety percent of screened women had HPV-negative NILM and an extremely low risk of subsequent cancer. Five-year risks of CIN 3+ were lower after HPV negativity (0.12%) than after NILM (0.25%). Among HPV-negative women, 5-year risks for CIN 3+ were 0.10% for NILM, 0.44% for ASC-US, 1.8% for LSIL, 3.0% for ASC-H, 1.2% for AGC, and 29% for HSIL+ cytology (which was very rare). Among HPV-positive women, 5-year risks were 4.0% for NILM, 6.8% for ASC-US, 6.1% for LSIL, 28% for ASC-H, 30% for AGC, and 50% for HSIL+ cytology. As a foundation for the next guidelines revision, we confirmed with additional precision the risk estimates previously reported for combinations of HPV and cytology. Future analyses will estimate risks for women being followed in colposcopy clinic and posttreatment and will consider the role of risk modifiers such as age, HPV vaccine status, HPV type, and screening and treatment history.

Association of Coloproctology of Great Britain & Ireland (ACPGBI): Guidelines for the Management of Cancer of the Colon, Rectum and Anus (2017) - Introduction.

Association of Coloproctology of Great Britain & Ireland (ACPGBI): Guidelines for the Management of Cancer of the Colon, Rectum and Anus (2017) - Introduction.

Gender disparity: Overlooking hereditary prostate cancer.

85 Background: Prostate cancer (PC) has been associated with germline mutations in several genes, most often BRCA2. Recently, 11.8% of men with metastatic PC were found to have germline mutations in BRCA and other DNA-repair genes. These mutations are equally inherited by men and women, both have elevated cancer risks, and National Comprehensive Cancer Network (NCCN) testing and management guidelines exist for male and female carriers. Despite this, over 95% of patients who have hereditary cancer multi-gene panel testing (MGPT) are women. We sought to describe detection rate and mutation spectrum of MGPT in men with PC compared to women with breast cancer (BC). Methods: Test results were reviewed for PC patients and female BC patients who had MGPT (Jun 2013 – May 2016) for up to 49 genes. Clinical history was obtained from test request forms. Results: Of 654 PC probands, 100 germline mutations were identified in 93 men (14.2%), significantly more than women with BC (8.6%; 6,215/71,728; p = 2.5e-5). Most mutations in PC patients were in BRCA (40.9%), followed by ATM (20.4%), CHEK2 (15.0%) and Lynch syndrome-associated genes (9.7%). Of the 100 total mutations, 94% were in genes that would impact management recommendations for them and/or their relatives. The median time from PC diagnosis to MGPT was 6 years, compared to 1 year for female BC. Nearly 57% (53/93) of mutation-positive men had multiple primary cancers, 79.2% of which had PC first. Of BRCA positives with multiple primaries (n = 21), over 90% developed PC followed by subsequent cancers, yet testing was not initiated until another cancer developed. Conclusions: In this cohort of men with PC, MGPT identified germline mutations at significantly higher rates than females with BC. Furthermore, 59.1% (55/93) of mutation positive PC probands had BRCA and/or ATM, making them possibly eligible for a PARP-inhibitor clinical trial. Unfortunately, time from PC diagnosis to MGPT was several years longer than women, allowing many to develop subsequent cancers that may have been prevented or detected earlier with knowledge of the germline mutation. Increased awareness among clinicians is needed to identify more male mutation carriers to enable appropriate cancer risk management for themselves and their relatives.

Comparison of UK and European Association of Urology (EAU) guidelines for kidney cancer management

Clinical practice frequently utilises guidelines on how specific conditions should be managed. For urologists in the UK a range of sources are used as guidelines for the management of kidney cancer. These include documents from national bodies such as the National Institute for Health and Care Excellence (NICE), professional bodies as well as those prepared by individual groups of clinicians within regional cancer networks. In this article the European Association of Urology (EAU) guidelines on renal cell carcinoma are compared to guidelines used in the UK for this disease. Broadly consistent variations exist related to regional practice patterns, funding and the currency of the various guidelines. A specific strength of the EAU guidelines is the regular updating of these allowing incorporation of new evidence. These however do not consider the funding model for healthcare of the UK which dictates the availability of some treatment modalities and thus in some areas are not applicable. Current guidelines for kidney cancer developed within the UK are inconsistent and often outdated in terms of evidence sources. Broader use of the EAU guidelines within the economic restrictions of healthcare in the UK may result in a more consistent practise utilising current evidence sources in the management of kidney cancer.

Guidelines for the Surgical Management of Laryngeal Cancer: Korean Society of Thyroid-Head and Neck Surgery.

Korean Society of Thyroid-Head and Neck Surgery appointed a Task Force to develop clinical practice guidelines for the surgical treatment of laryngeal cancer. This Task Force conducted a systematic search of the EMBASE, MEDLINE, Cochrane Library, and KoreaMed databases to identify relevant articles, using search terms selected according to the key questions. Evidence-based recommendations were then created on the basis of these articles. An external expert review and Delphi questionnaire were applied to reach consensus regarding the recommendations. The resulting guidelines focus on the surgical treatment of laryngeal cancer with the assumption that surgery is the selected treatment modality after a multidisciplinary discussion in any context. These guidelines do not, therefore, address non-surgical treatment such as radiation therapy or chemotherapy. The committee developed 62 evidence-based recommendations in 32 categories intended to assist clinicians during management of patients with laryngeal cancer and patients with laryngeal cancer, and counselors and health policy-makers.

Practice guidelines for management of cervical cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement.

Clinical practice guidelines for gynecologic cancers have been developed by academic society from several countries. Each guideline reflected their own insurance system and unique medical environment, based on the published evidence. The Korean Society of Gynecologic Oncology (KSGO) published the first edition of practice guidelines for gynecologic cancer treatment in late 2006; the second edition was released in July 2010 as an evidence-based recommendation. The Guidelines Revision Committee was established in 2015 and decided to develop the third edition of the guidelines in an advanced format based on evidence-based medicine, embracing up-to-date clinical trials and qualified Korean data. These guidelines cover strategies for diagnosis and treatment of primary and recurrent cervical cancer. The committee members and many gynecologic oncologists derived key questions through discussions, and a number of relevant scientific literature were reviewed in advance. Recommendations for each specific question were developed by the consensus conference, and they are summarized here, along with the details. The objective of these practice guidelines is to establish standard policies on issues in clinical practice related to the management in cervical cancer based on the results in published papers to date and the consensus of experts as a KSGO Consensus Statement.

Saudi lung cancer management guidelines 2017.

BACKGROUND:Lung cancer management is getting more complex due to the rapid advances in all aspects of diagnostic and therapeutic options. Developing guidelines is critical to help practitioners provide standard of care.METHODS:The Saudi Lung Cancer Guidelines Committee (SLCGC) multidisciplinary members from different specialties and from various regions and healthcare sectors of the country reviewed and updated all lung cancer guidelines with appropriate labeling of level of evidence. Supporting documents to help healthcare professionals were developed.RESULTS:Detailed lung cancer management guidelines were finalized with appropriate resources for systemic therapy and short reviews highlighting important issues. Stage based disease management recommendation were included. A summary explanation for complex topics were included in addition to tables of approved systemic therapy.CONCLUSION:A multidisciplinary lung cancer guidelines was developed and will be disseminated across the country.

Thyroid nodules and cancer management guidelines: comparisons and controversies.

Thyroid cancer is an increasingly prevalent malignancy throughout the world. Management guidelines for both thyroid nodules and thyroid cancer have been published and updated by a number of societies internationally. All of these guidelines recognize this increasing incidence, particularly of small papillary thyroid cancers, due in part to improved technology enabling early or even 'over' diagnosis. Recent advances in molecular imaging and molecular methods have been developed to better characterize thyroid nodules, and a number of studies that have clarified risk stratification systems that can be modified over time allow for individualization of diagnosis, initial treatment, and subsequent follow-up strategies. Advances in surgical approaches and new treatments for patients with the most aggressive forms of thyroid cancer have all influenced management guidelines. Despite substantial similarities, there also are important differences between recent guidelines for some of the common clinical scenarios encountered by physicians in clinical practice. In the present manuscript, we will highlight similarities and differences between several of the most recently published guidelines focused on key areas of importance to clinical care and controversy. These are key areas for future research to strengthen the data to support future guideline recommendations.

Practice guidelines for management of uterine corpus cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement.

Clinical practice guidelines for gynecologic cancers have been developed by many organizations. Although these guidelines have much in common in terms of the practice of standard of care for uterine corpus cancer, practice guidelines that reflect the characteristics of patients and healthcare and insurance systems are needed for each country. The Korean Society of Gynecologic Oncology (KSGO) published the first edition of practice guidelines for gynecologic cancer treatment in late 2006; the second edition was released in July 2010 as an evidence-based recommendation. The Guidelines Revision Committee was established in 2015 and decided to produce the third edition of the guidelines as an advanced form based on evidence-based medicine, considering up-to-date clinical trials and abundant qualified Korean data. These guidelines cover screening, surgery, adjuvant treatment, and advanced and recurrent disease with respect to endometrial carcinoma and uterine sarcoma. The committee members and many gynecologic oncologists derived key questions from the discussion, and a number of relevant scientific literatures were reviewed in advance. Recommendations for each specific question were developed by the consensus conference, and they are summarized here, together with other details. The objective of these practice guidelines is to establish standard policies on issues in clinical areas related to the management of uterine corpus cancer based on the findings in published papers to date and the consensus of experts as a KSGO Consensus Statement.

Significance of coexistent granulomatous inflammation and lung cancer

AimsCoexistence of lung cancer and granulomatous inflammation in the same patient confuses clinicians. We aimed to document the prevalence, clinicopathological features, treatment outcomes and prognosis in patients with coexisting granulomatous...

Resource-Stratified Guidelines for Cancer Management: Correction and Commentary.

Resource-Stratified Guidelines for Cancer Management: Correction and Commentary.

Multi-gene panel testing for hereditary cancer susceptibility in a rural Familial Cancer Program.

This study explores our Familial Cancer Program's experience implementing multi-gene panel testing in a largely rural patient population. We conducted a retrospective review of patients undergoing panel testing between May 2011 and August 2015. Our goal was to evaluate factors that might be predictors of identifying variants (pathogenic or uncertain significance) and to assess clinical management changes due to testing. We utilized a structured family history tool to determine the significance of patient's family histories with respect to identification of genetic variants. A total of 227 patients underwent panel testing at our center and 67 patients (29.5%) had variants identified, with 8 (3.5%) having multiple variants. Overall, 44 patients (19.4%) had a variant of uncertain significance (VUS) and 28 patients (12.3%) had a pathogenic variant detected, with 10 (4.4%) having pathogenic variants in highly penetrant genes. We found no statistical difference in patient familial and personal cancer history, age, rural status, Ashkenazi Jewish ancestry, insurance coverage and prior single-gene testing among those with pathogenic, VUS and negative panel testing results. There were no predictors of pathogenic variants on regression analysis. Panel testing changed cancer screening and management guidelines from that expected based on family history alone in 13.2% of patients. Ultimately, cancer panel testing does yield critical information not identified by traditional single gene testing but maximal utility through a broad range of personal and family histories requires improved interpretation of variants.

National Evaluation of Hospital Performance on the New Commission on Cancer Melanoma Quality Measures.

To increase adherence to cancer management guidelines, the Commission on Cancer (CoC) developed and approved five melanoma quality measures in 2015. Our objectives were to evaluate formally the national performance of these melanoma measures and to examine patient, tumor, and hospital characteristics associated with adherence. From the National Cancer Data Base (2012), patients with invasive, nonmetastatic melanoma were identified. Inclusion and exclusion criteria were based on the CoC definition for each measure. Patient-level and hospital-level adherence rates were calculated for the five measures. A hospital was deemed "compliant" if it met the CoC standard, which requires 80% of patients to receive the measure-specific recommended care. Patient, tumor, and hospital characteristics potentially associated with higher likelihood of adherence at the patient-level were estimated using hierarchical random-effects logistic regression models. A total of 31,598 patients from 1343 hospitals were examined. Patient-level adherence rates varied from 31.6% (Measure 5: ≥10 axillary lymph nodes removed/examined) to 72.6% (Measure 1: sentinel lymph node biopsy (SLNB) appropriateness measure). Hospital-level adherence rates, ranged from 19.3% of hospitals (N=538 hospitals for Measure 5) to 44.8% of hospitals (N=1090 hospitals for Measure 3: completion lymph node dissection after positive SLNB). No hospital-level factors (e.g., teaching status) were consistently associated with better adherence. National adherence rates to the five new CoC melanoma quality metrics are low, and most hospitals would not meet the CoC requirement of 80% adherence. Feedback for performance of these measures to hospitals, decisions support tools, and educational initiatives are needed to improve guideline adherence.

A Review of Squamous Cell Vulvar Cancers in Waikato Region, New Zealand.

e17032Background: Squamous cell vulvar cancer management guidelines are scarce. The objectives of the study were to review the patient characteristics and outcomes of vulvar cancers. Methods: Retro...

MP13-02 IS RE-RESECTION NECESSARY? RE-RESECTION OF NON-MUSCLE INVASIVE BLADDER CANCER AT A TERTIARY CARE CENTER

You have accessJournal of UrologyBladder Cancer: Non-Invasive I1 Apr 2016MP13-02 IS RE-RESECTION NECESSARY? RE-RESECTION OF NON-MUSCLE INVASIVE BLADDER CANCER AT A TERTIARY CARE CENTER Rano Matta, Ashraf Al Matar, Bimal Bhindi, Alexander Zlotta, Neil Fleshner, Michael Jewett, Robert Hamilton, Antonio Finelli, and Girish Kulkarni Rano MattaRano Matta More articles by this author , Ashraf Al MatarAshraf Al Matar More articles by this author , Bimal BhindiBimal Bhindi More articles by this author , Alexander ZlottaAlexander Zlotta More articles by this author , Neil FleshnerNeil Fleshner More articles by this author , Michael JewettMichael Jewett More articles by this author , Robert HamiltonRobert Hamilton More articles by this author , Antonio FinelliAntonio Finelli More articles by this author , and Girish KulkarniGirish Kulkarni More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2483AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Re-staging transurethral resection (re-TUR) of T1 bladder tumors provides more accurate staging, and is associated with better local control. Re-TUR has been included in guidelines for management of non-muscle invasive bladder cancer since 2007. However, in practice, re-TUR has been questioned in the setting of perceived complete resection at initial TUR, amongst other patient and surgeon specific factors. We aimed to understand the practice patterns of re-TUR of T1 urothelial carcinoma at our center and its predictors. We also determined outcomes associated with re-TUR at a Canadian tertiary care center. METHODS We retrospectively identified 358 consecutive patients with pT1 high grade urothelial carcinoma of the bladder who were treated at the University Health Network, Toronto, from 2000 to 2012. We excluded those who had metastatic disease on diagnosis, those treated primarily with cystectomy or chemotherapy/radiation after TURBT. Those treated with early cystectomy or chemotherapy/radiation after re-TUR were not included in the final cohort. Patients who did not undergo immediate/early cystectomy were offered adjuvant BCG therapy. The remaining 270 patients were included in the final analysis. We compared re-TUR rates in the pre- (2000-2008) and post-guideline (2009-2012) era. End points were time to recurrence, time to progression (defined as stage T2 or higher), and mortality. Univariate and multivariate analyses were used to determine any significant effect of patient specific factors (age, gender) and disease specific factors (associated CIS, muscle sampled, immediate chemotherapy) on proceeding for re-TUR. We also performed Cox-proportional hazard models to determine risk factors for recurrence, progression, and survival. RESULTS The median age of the cohort was 68.9 years (18-97) with a mean follow up 3.3 years (0.08-13.3 years). Re-TUR was performed in 109 patients (40%). The average re-TUR rate increased after 2008 from 31.6% to 51.3% (p=0.038). There was residual tumor in 70% of re-TUR cases. Upstaging to T2 disease on re-TUR was seen in 16.5% of patients. There was residual pT1 in 29.4% of cases. Residual T1 disease at re-TUR was a significant risk factor for progression (HR 38.1; CI 5.9-246.6). Re-TUR was not a significant risk factor for recurrence, progression or mortality. CONCLUSIONS Overall, re-TUR is an important therapy, decision-making and prognostication tool in NMIBC. However, in terms of the effectiveness of re-TUR on recurrence and progression, further prospective studies will provide more definitive information. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e134 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Rano Matta More articles by this author Ashraf Al Matar More articles by this author Bimal Bhindi More articles by this author Alexander Zlotta More articles by this author Neil Fleshner More articles by this author Michael Jewett More articles by this author Robert Hamilton More articles by this author Antonio Finelli More articles by this author Girish Kulkarni More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Cervical Cancer Screening

Recent changes in cervical cancer screening and management guidelines reflect our evolving knowledge about cervical carcinogenesis. In the pursuit of precision, however, decision-making has become complicated. We provide an overview of cervical cancer screening with a focus on what clinicians can do to maximize screening benefits while minimizing screening harms. The approach relies on categorizing women at each step in the screening process by their estimated risk of high-grade precancerous lesions and cervical cancer. Current screening guidelines are designed to find a reasonable balance between benefits and harms by recommending less screening in most women. Current management guidelines are designed to assure consistent decisions regarding referral to colposcopy. After initial colposcopy, we outline three major management options based on risk assessment. For treatment, we recommend ablational procedures when appropriate because they are similarly effective, less costly, and potentially safer than excisional procedures. We advise caution in adopting new screening strategies until they demonstrate cost-effective patient-centered improvements compared with current strategies. Clinicians can maximize their effect on cervical cancer prevention by being attentive to guidelines, assuring that women have access to appropriate human papillomavirus vaccination and providing low-cost, high-quality screening and treatment.

International Association of Pancreatology (IAP)/European Pancreatic Club (EPC) consensus review of guidelines for the treatment of pancreatic cancer.

Pancreatic cancer is one of the most devastating diseases with an extremely high mortality. Medical organizations and scientific societies have published a number of guidelines to address active treatment of pancreatic cancer. The aim of this consensus review was to identify where there is agreement or disagreement among the existing guidelines and to help define the gaps for future studies. A panel of expert pancreatologists gathered at the 46th European Pancreatic Club Meeting combined with the 18th International Association of Pancreatology Meeting and collaborated on critical reviews of eight English language guidelines for the clinical management of pancreatic cancer. Clinical questions (CQs) of interest were proposed by specialists in each of nine areas. The recommendations for the CQs in existing guidelines, as well as the evidence on which these were based, were reviewed and compared. The evidence was graded as sufficient, mediocre or poor/absent. Only 4 of the 36 CQs, had sufficient evidence for agreement. There was also agreement in five additional CQs despite the lack of sufficient evidence. In 22 CQs, there was disagreement regardless of the presence or absence of evidence. There were five CQs that were not addressed adequately by existing guidelines. The existing guidelines provide both evidence- and consensus-based recommendations. There is also considerable disagreement about the recommendations in part due to the lack of high level evidence. Improving the clinical management of patients with pancreatic cancer, will require continuing efforts to undertake research that will provide sufficient evidence to allow agreement.