Background
Methods
Stage 1 – Identify a body of trials
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The trial focused on the treatment of breast cancer or the management of side effects/consequences of the treatment, or the trial focused on the treatment and/or management of any nephrology-related illness some of which included dialysis patients, e.g. polycystic kidney disease, acute kidney injury, chronic kidney disease, progressive membranous nephropathy, diabetic kidney disease, end-stage renal disease, etc.
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The trial was phase 3 or 4 (breast cancer), or phase 2, 3 or 4 (nephrology)
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The trial could be industry- or academic-led
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The trial had to clearly report primary and secondary outcomes
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The trial results were published between 01/01/2015 and 31/12/2018 (breast cancer) and 01/01/2010 and 31/12/2019 (nephrology)
Stage 2 — Identifying primary and secondary outcomes
Data extraction |
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Trial reference |
Brief description of the intervention being tested (plain language) |
Brief description of the study population |
Primary outcome(s) including a short definition |
Secondary outcome 1 (including a short definition) |
Secondary outcome 2 (including a short definition) |
Secondary outcome 3 (including a short definition) |
Secondary outcome 4 (including a short definition) |
Etc… |
Stage 3 – Presenting the trials and outcomes to patients and healthcare professionals
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Medical and clinical oncologists
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Surgeons
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Radiologists
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Breast care nurses
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Representatives from cancer organisations
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Representatives from patient advocacy groups
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People who have, or have had, breast cancer
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Consultant nephrologists
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Registrar in nephrology
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Renal dietician
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Patients who attend an outpatient nephrology clinic
Breast cancer management (10 individuals) | |
Stakeholder’s category | Country |
Breast cancer surgeon representative from a Clinical Oncology Society | Brazil |
Pharmacist representative from a Clinical Oncology Society | Brazil |
Clinical oncologist × 2 | Brazil |
Breast cancer surgeon | UK |
Breast cancer surgeon | USA |
Radiologist and professor of breast imaging | UK |
Person who has had treatment for breast cancer × 2 | UK |
Representative of a Cancer Patient Advocacy Group | Brazil |
Nephrology (32 individuals) | |
Stakeholder’s category | Country |
Consultant nephrologist × 3 | Ireland |
Registrar in nephrology × 1 | Ireland |
Renal dietician × 1 | Ireland |
Patients who attend an outpatient nephrology clinic × 27 | Ireland |
Analysis
Results
Stages 1 and 2
Stage 3
Trial ID | Primary outcome | Number of responses to trial | Number of outcomes | Median ranking of primary [range] | Number of times primary was within respondents’ top 5 outcomes | Outcome(s) with highest ranked median | Median ranking of highest placed outcome [range] |
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Trial 1 | Locally investigator-assessed progression-free survival | 10 | 6 | 3 [2–unranked] | 9 | Overall survival | 1 [1–unranked] |
HCPs | 7 | 4 [3–unranked] | 6 | Overall survival | 1 [1–unranked] | ||
Patients | 3 | 2 [2-2] | 3 | Overall survival | 1 [1-2] | ||
Trial 2 | Survival without distant metastasis at 5 years (time from trial randomisation until the first distant metastatic recurrence, or death from any cause) | 11 | 4 | 3 [1-5] | 11 | Overall survival (time from trial randomisation until death from any cause) Disease-free survival (time from trial randomisation until first disease progression or death from any cause) | 2 [1-5] 2 [1-5] |
HCPs | 8 | 3.5 [1-5] | 8 | Overall survival (time from trial randomisation until death from any cause) | 2 [1-5] | ||
Patients | 3 | 2 [1-3] | 3 | Disease-free survival (time from trial randomisation until first disease progression or death from any cause) | 1 [1,2] | ||
Trial 3 | Invasive disease-free survival at 2-year follow-up. Defined as the time from randomisation to any of the following: invasive tumour recurrence (same side as the original tumour), invasive breast cancer (opposite side), local or wider invasive recurrence, more distant recurrence, death from any cause | 10 | 7 | 2.5 [1–unranked] | 4 | Overall survival (time from randomisation to death) | 2 [1–unranked] |
HCPs | 7 | 3 [2–unranked] | 6 | Overall survival (time from randomisation to death) | 2 [1-5] | ||
Patients | 3 | 1 [1–unranked] | 1 | Invasive disease-free survival at 2-year follow-up. Defined as the time from randomisation to any of the following: invasive tumour recurrence (same side as the original tumour), invasive breast cancer (opposite side), local or wider invasive recurrence, more distant recurrence and death from any cause Cumulative incidence of central nervous system (CNS) cancer recurrences (time from randomisation to CNS recurrence as first distant recurrence) Safety | 1 [1–unranked] 1 [1–unranked] 1 [1–unranked] | ||
Trial 4 | Overall survival (time from randomisation to death from any cause) | 9 | 4 | 2 [1-5] | 9 | Health-related quality of life | 1 [1.5–unranked] |
HCPs | 6 | 2.5 [1-5] | 6 | Health-related quality of life | 1.5 [1-4] | ||
Patients | 3 | 1 [1-2] | 3 | Overall survival (time from randomisation to death from any cause) | 1 [1-2] | ||
Trial 5 | Overall survival (time from randomisation to death from any cause) | 9 | 5 | 2 [1–unranked] | 6 | Difference between treatment groups in the change in systolic automated office blood pressure from baseline to week 12 | 2 [1-7] |
HCPs | 6 | 1 [1–unranked] | 5 | Difference between treatment groups in the change in systolic automated office blood pressure from baseline to week 12 | 2 [1-5] | ||
Patients | 3 | 3 [3–unranked] | 1 | Cumulative incidence of regional recurrence and distant metastasis (i.e. that has spread) Survival time | 1 [1-1] 1 [1-2] | ||
Trial 6 | Breast cancer-free interval (time from randomisation to any breast cancer event censored for deaths) | 9 | 12 | 3 [1–unranked] | 7 | Vaginal symptoms (vaginal dryness and pain with intercourse) Disease-free survival (time to any recurrence excluding lobular carcinoma in situ, second primary cancer and death from any cause) Quality of life | 2 [1–unranked] 2 [1–unranked] 2 [2-5] |
HCPs | 6 | 3.5 [2–unranked] | 4 | Quality of life | 2 [2-4] | ||
Patients | 3 | 2 [1-3] | 3 | Vaginal symptoms (vaginal dryness and pain with intercourse) Disease-free survival (time to any recurrence excluding lobular carcinoma in situ, second primary cancer and death from any cause) Contralateral breast cancer Osteoporotic fractures Vasomotor symptoms Sexual functioning | 1 [1–unranked] 1 [1-2] 1 [1–unranked] 1 [1–unranked] 1 [1–unranked] 1 [1–unranked] | ||
Trial 7 | Pathological complete response of the primary tumour in the breast (absence of histological evidence of invasive tumour cells in the breast sample removed at surgery) | 8 | 5 | 2 [1-5] | 8 | Disease-free survival (time from randomisation to disease recurrence, or death) | 1 [1–unranked] |
HCPs | 5 | 2 [1-5] | 5 | Pathological complete response of the primary tumour in the breast (absence of histological evidence of invasive tumour cells in the breast sample removed at surgery) | 2 [1-5] | ||
Patients | 3 | 2 [2-2] | 5 | Disease-free survival (time from randomisation to disease recurrence, or death) | 1 [1-1] | ||
Trial 8 [**Primary outcome match**] | Disease-free survival (time from randomisation to the date of one of the following (whichever came first): local recurrence, distant metastases — i.e. cancer that has spread, contralateral or ipsilateral breast tumor (excluding ductal carcinoma in situ — i.e. cancer that has not spread), second primary malignancy, death from any cause, loss to follow-up or end of the study | 9 | 3 | 2 [1-4] | 9 | Disease-free survival (time from randomisation to the date of one of the following (whichever came first): local recurrence, distant metastases — i.e. cancer that has spread, contralateral or ipsilateral breast tumor (excluding ductal carcinoma in situ — i.e. cancer that has not spread), second primary malignancy, death from any cause, loss to follow-up or end of the study Overall survival (time from randomisation to the date of death from any cause, loss to follow-up or the end of study) | 2 [1-4] 2 [1-5] |
HCPs | 6 | 2 [1-4] | 6 | Overall survival (time from randomisation to the date of death from any cause, loss to follow-up or the end of study) | 1.5 [1-5] | ||
Patients | 3 | 1 [1-2] | 3 | Disease-free survival (time from randomisation to the date of one of the following (whichever came first): local recurrence, distant metastases — i.e. cancer that has spread, contralateral or ipsilateral breast tumor (excluding ductal carcinoma in situ — i.e. cancer that has not spread), second primary malignancy, death from any cause, loss to follow-up or end of the study | 1 [1-2] | ||
Trial 9 | Time-to-event analysis of the rate of survival free from invasive cancer (first event of recurrence of one of the following: ipsilateral breast tumour, local recurrence, regional recurrence, distant recurrence, contralateral second primary invasive cancer, second primary non-breast invasive cancer (excluding non-melanoma skin cancer), or death without evidence of recurrence)) | 8 | 4 | 3 [1–unranked] | 7 | Overall survival rate (proportion of patients who did not die from any cause) Freedom from any recurrence (first recurrence of breast cancer at any site or death with recurrence) | 2 [1–unranked] 2 [1–unranked] |
HCPs | 6 | 3 [1–unranked] | 5 | Overall survival rate (proportion of patients who did not die from any cause) Freedom from any recurrence (first recurrence of breast cancer at any site or death with recurrence) | 2 [1–unranked] 2 [1–unranked] | ||
Patients | 2 | 3 [3-3] | 2 | Freedom from any recurrence (first recurrence of breast cancer at any site or death with recurrence) | 2 [2-2] | ||
Trial 10 [**Primary outcome match**] | Progression-free survival (determined based on investigator’s assessments according to response evaluation criteria in solid tumours, or surgery or radiotherapy for worsening of disease, or death from any cause) | 8 | 10 | 2 [1–unranked] | 7 | Clinical benefit rate (best overall response of complete response, partial response, or stable disease ≥ 24 weeks) Progression-free survival (determined based on investigator’s assessments according to response evaluation criteria in solid tumours, or surgery or radiotherapy for worsening of disease, or death from any cause) | 2 [1–unranked] 2 [1–unranked] |
HCPs | 5 | 2.5 [2–unranked] | 4 | Objective response rate (best overall response of either complete response or partial response in patients with measurable disease at baseline) | 2 [1–unranked] | ||
Patients | 3 | 1 [1-2] | 3 | Progression-free survival (determined based on investigator’s assessments according to response evaluation criteria in solid tumours, or surgery or radiotherapy for worsening of disease, or death from any cause) Health-related quality of life | 1 [1-2] 1 [1–unranked] | ||
Trial 11 [**Primary outcome match**] | All recurrence (development of histologically confirmed breast cancer both invasive and new or recurrent ductal carcinoma in situ (DCIS)) | 9 | 8 | 1 [1–unranked] | 7 | All recurrence (development of histologically confirmed breast cancer both invasive and new or recurrent ductal carcinoma in situ (DCIS)) | 1 [1–unranked] |
HCPs | 6 | 1.5 [1–unranked] | 4 | All recurrence (development of histologically confirmed breast cancer both invasive and new or recurrent ductal carcinoma in situ (DCIS)) | 1.5 [1–unranked] | ||
Patients | 3 | 1 [1-1] | 3 | All recurrence (development of histologically confirmed breast cancer both invasive and new or recurrent ductal carcinoma in situ (DCIS)) | 1 [1-1] | ||
Trial 12 | Overall survival (time from randomisation to death from any cause) | 9 | 8 | 2 [1-5] | 9 | Progression-free survival (time from randomisation to disease progression or death from any cause) | 1 [1-5] |
HCPs | 6 | 2 [1-5] | 6 | Progression-free survival (time from randomisation to disease progression or death from any cause) | 1.5 [1-5] | ||
Patients | 3 | 2 [2-2] | 3 | Progression-free survival (time from randomisation to disease progression or death from any cause) | 1 [1-1] | ||
Trial 13: primary 1 | Investigator-assessed progression-free survival (time from randomisation to first documented disease progression according to RECIST or death from any cause) | 8 | 10 | 2.5 [1–unranked] | 6 | Overall survival (interval from randomisation to death from any cause) | 1.5 [1-5] |
HCPs | 6 | 3 [2–unranked] | 4 | Overall survival (interval from randomisation to death from any cause) | |||
Patients | 2 | 1.5 [1-2] | 2 | Investigator-assessed progression-free survival (time from randomisation to first documented disease progression according to RECIST or death from any cause) Overall survival (interval from randomisation to death from any cause) | 1.5 [1-2] 1.5 [1-2] | ||
Trial 13: primary 2 [**Primary outcome match**] | Overall survival (interval from randomisation to death from any cause) | 8 | 10 | 1.5 [1-5] | 8 | Overall survival (interval from randomisation to death from any cause) | 1.5 [1-5] |
HCPs | 6 | 1.5 [1-5] | 6 | Overall survival (interval from randomisation to death from any cause) | 1.5 [1-5] | ||
Patients | 2 | 1.5 [1-2] | 2 | Investigator-assessed progression-free survival (time from randomisation to first documented disease progression according to RECIST or death from any cause) Overall survival (interval from randomisation to death from any cause) | 1.5 [1-2] 1.5 [1-2] | ||
Trial 14 | 5-year disease-free survival (date of randomisation to the date of first relapse, to the date of death in women dying without relapse or to the date of censor in women alive and relapse-free) | 8 | 7 | 1.5 [1–unranked] | 4 | 10-year disease-free survival | 1 [1–unranked] |
HCPs | 6 | 3 [2-3] | 5 | 10-year disease-free survival | 1 [1–unranked] | ||
Patients | 2 | 4 [3-7] | 4 | 5-year disease-free survival (date of randomisation to the date of first relapse, to the date of death in women dying without relapse or to the date of censor in women alive and relapse-free) | 1 [1–unranked] | ||
Trial 15 | Pathological complete response (absence of invasive breast cancer in the breast and axillary lymph nodes, after neoadjuvant chemotherapy) | 8 | 4 | 2.5 [1-5] | 8 | Disease-free survival | 1 [1–unranked] |
HCPs | 6 | 2 [1-5] | 6 | Disease-free survival | 1.5 [1–unranked] | ||
Patients | 2 | 3 [3-3] | 2 | Disease-free survival | 1 [1] | ||
Trial 16 [**Primary outcome match**] | Progression-free survival (time from trial randomisation until the first progression of the cancer, or death due to any cause, whichever occurred first) | 8 | 9 | 2 [1–unranked] | 7 | Overall survival (time from randomisation to the date of death due to any cause) Quality of life Progression-free survival (time from trial randomisation until the first progression of the cancer, or death due to any cause, whichever occurred first) Clinical benefit (proportion of patients whose final response to treatment is judged to be (a) complete response or (b) partial response, or who have stable cancer for ≥ 24 weeks) | 2 [1–unranked] 2 [1–unranked] 2 [1–unranked] 2 [1–unranked] |
HCPs | 6 | 2 [1–unranked] | 5 | 1) Overall survival (time from randomisation to the date of death due to any cause) 2) Clinical benefit (proportion of patients whose final response to treatment is judged to be a) complete response or b) partial response, or who have stable cancer for ≥ 24 weeks) | 1 [1–unranked] 1 [1–unranked] | ||
Patients | 2 | 2 [1-3] | 2 | 1) Overall survival (time from randomisation to the date of death due to any cause) 2) Progression-free survival (time from trial randomisation until the first progression of the cancer, or death due to any cause, whichever occurred first) | 2 [2-2] 2 [1-3] | ||
Trial 17 [**Primary outcome match**] | Occurrence of any type of breast cancer (including ductal carcinoma in situ — i.e. cancer that has not spread) | 8 | 4 | 1.5 [1-5]] | 8 | Occurrence of any type of breast cancer (including ductal carcinoma in situ — i.e. cancer that has not spread) | 1.5 [1-5] |
HCPs | 6 | 1.5 [1-5] | 6 | Occurrence of any type of breast cancer (including ductal carcinoma in situ — i.e. cancer that has not spread) | 1.5 [1-5] | ||
Patients | 2 | 1.5 [1-2] | 2 | Occurrence of any type of breast cancer (including ductal carcinoma in situ — i.e. cancer that has not spread) Occurrence of invasive oestrogen receptor-positive breast cancer | 1.5 [1-2] 1.5 [1-2] | ||
Trial 18 [**Primary outcome match**] | Invasive disease-free survival (time from randomisation until the date of the first occurrence of one of the following events: recurrence of ipsilateral invasive breast tumor, recurrence of ipsilateral locoregional invasive breast cancer, contralateral invasive breast cancer, a distant disease recurrence or death from any cause) | 8 | 6 | 2 [1–unranked] | 5 | Invasive disease-free survival (time from randomisation until the date of the first occurrence of one of the following events: recurrence of ipsilateral invasive breast tumor, recurrence of ipsilateral locoregional invasive breast cancer, contralateral invasive breast cancer, a distant disease recurrence or death from any cause) Overall survival Safety Disease-free survival (including noninvasive breast cancers) | 2 [1–unranked] 2 [1–unranked] 2 [2–unranked] 2 [1–unranked] |
HCPs | 6 | 2.5 [1–unranked] | 4 | Overall survival | 1 [1-5] | ||
Patients | 2 | 1 [1-1] | 1 | Invasive disease-free survival (time from randomisation until the date of the first occurrence of one of the following events: recurrence of ipsilateral invasive breast tumor, recurrence of ipsilateral locoregional invasive breast cancer, contralateral invasive breast cancer, a distant disease recurrence or death from any cause) | 1 [1-1] | ||
Trial 19 [**Primary outcome match**] | Investigator-assessed progression-free survival (time from randomisation to radiologically confirmed disease progression according to RECIST, version 1.1, or death during the study) | 7 | 8 | 2 [1-4] | 7 | Clinical benefit response (defined as a confirmed complete response, a partial response or stable disease for ≥ 24 weeks) Investigator-assessed progression-free survival (time from randomisation to radiologically confirmed disease progression according to RECIST, version 1.1, or death during the study) | 2 [1–unranked] 2 [1-4] |
HCPs | 5 | 3 [1-4] | 5 | Clinical benefit response (defined as a confirmed complete response, a partial response or stable disease for ≥ 24 weeks) Overall survival objective response (defined as confirmed complete response or partial response) Patient-reported outcomes (assessed by health-related quality-of-life scores) | 2 [2–unranked] 2 [1–unranked] 2 [2-3] | ||
Patients | 2 | 1.5 [1-2] | 2 | Investigator-assessed progression-free survival (time from randomisation to radiologically confirmed disease progression according to RECIST, version 1.1, or death during the study) | 1.5 [1-2] | ||
Trial 20 | Overall survival (time from randomisation to the date of death from any cause) | 8 | 4 | 2 [1–unranked] | 7 | Disease-free survival (time from randomisation to the first date of local recurrence, regional recurrence, distant recurrence, second breast cancer or death from any cause, whichever occurred first) | 1 [1–unranked] |
HCPs | 6 | 2 [1–unranked] | 5 | Disease-free survival (time from randomisation to the first date of local recurrence, regional recurrence, distant recurrence, second breast cancer or death from any cause, whichever occurred first) Overall survival (time from randomisation to the date of death from any cause) Distant disease-free survival (time from randomisation to the first date of distant disease or death from any cause, whichever occurred first) | 2 [1–unranked] 2 [1–unranked] 2 [1-5] | ||
Patients | 2 | 3.5 [3-4] | 2 | Disease-free survival (time from randomisation to the first date of local recurrence, regional recurrence, distant recurrence, second breast cancer or death from any cause, whichever occurred first) | 1 [1-1] |
Trial ID | Primary outcome | Number of responses to trial | Number of outcomes | Median ranking of primary [range] | Number of times primary was within respondents’ top 5 outcomes | Outcome(s) with highest ranked median | Median ranking of highest placed outcome [range] |
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Trial 1 [**Primary outcome match**] | End-stage renal disease or death from cardiovascular causes | 11 | 4 | 1 [1-4] | 11 | End-stage renal disease or death from cardiovascular causes | 1 [1-4] |
HCPs | 5 | 1 [1-3] | 4 | 1 [1-3] | |||
Patients | 6 | 1.5 [1-4] | 6 | 1.5 [1-4] | |||
Trial 2 | Mean change from the baseline haemoglobin level to the mean level during the evaluation period | 11 | 3 | 2 [1-3] | 11 | Mean change from the baseline haemoglobin level to the mean level during the evaluation period Proportion of patients in whom there was a response in haemoglobin levels Proportion of patients receiving a transfusion | 2 [1-3] 2 [1-3] 2 [1-3] |
HCPs | 6 | 2 [1-3] | 6 | Mean change from the baseline haemoglobin level to the mean level during the evaluation period | 1 [1-3] | ||
Patients | 5 | 1 [1-3] | 4 | 1) Mean change from the baseline haemoglobin level to the mean level during the evaluation period 2) Proportion of patients in whom there was a response in haemoglobin levels 3) Proportion of patients receiving a transfusion | 2 [1-3] 2 [1-3] 2 [1-3] | ||
Trial 3 | Occurrence of a major cardiovascular or renal event | 10 | 9 | 4 [1-9] | 8 | 1) Occurrence of a major cardiovascular or renal event 2) Need for dialysis or transplantation 3) Worsening of kidney function | 4 [1-9] 4 [1-6] 4 [1-9] |
HCPs | 5 | 3 [1-5] | 5 | All-cause mortality | 1 [1-6] | ||
Patients | 5 | 4 [3-9] | 3 | Need for dialysis or transplantation | 1 [1-6] | ||
Trial 4 | Difference between treatment groups in the proportion of patients remaining on spironolactone at week 12 | 11 | 7 | 5 [1-7] | 6 | Difference between treatment groups in the change in systolic automated office blood pressure from baseline to week 12 | 2 [1-7] |
HCPs | 5 | 5 [1-6] | 3 | Difference between treatment groups in the change in systolic automated office blood pressure from baseline to week 12 | 2 [1-5] | ||
Patients | 6 | 5.5 [2-7] | 3 | Patient-reported outcomes as measured by the EQ-5D-5L questionnaire | 1.5 [1-7] | ||
Trial 5 | Independence from dialysis at 90 days after random allocation to groups | 10 | 5 | 3.5 [1-5] | 10 | Overall survival at the end of the study | 1 [1-5] |
HCPs | 5 | 3 [1-4] | 5 | Overall survival at the end of the study | 1 [1-5] | ||
Patients | 5 | 4 [1-5] | 5 | Overall survival at the end of the study | 1 [1-5] | ||
Trial 6 [**Primary outcome match**] | A composite of death from any cause by 28 days after randomisation and the presence of at least one organ failure at 7 days after randomization | 10 | 7 | 1 [1-3] | 10 | A composite of death from any cause by 28 days after randomisation and the presence of at least one organ failure at 7 days after randomization | 1 [1-3] |
HCPs | 5 | 1 [1-1] | 5 | A composite of death from any cause by 28 days after randomisation and the presence of at least one organ failure at 7 days after randomization | 1 [1-1] | ||
Patients | 5 | 2 [1-3] | 5 | A composite of death from any cause by 28 days after randomisation and the presence of at least one organ failure at 7 days after randomization | 2 [1-3] | ||
Trial 7 | A ranking of clinical outcomes, maximum relative change in creatinine, dialysis, and death, within 7 days of randomization | 10 | 6 | 2.5 [1-5] | 10 | Death | 2 [1-6] |
HCPs | 5 | 2 [2-5] | 5 | Death | 1 [1-4] | ||
Patients | 5 | 3 [1-5] | 5 | Progression to higher stages of acute kidney injury | 2 [1-6] | ||
Trial 8 [**Primary outcome match**] | A further 20% decline in excretory renal function from baseline readings | 10 | 3 | 1 [1-2] | 10 | A further 20% decline in excretory renal function from baseline readings | 1 [1-2] |
HCPs | 5 | 1 [1-2] | 5 | A further 20% decline in excretory renal function from baseline readings | 1 [1-2] | ||
Patients | 5 | 1 [1-1] | 5 | A further 20% decline in excretory renal function from baseline readings | 1 [1-1] | ||
Trial 9 | Relapse-free survival based on the period of time until the first relapse | 10 | 3 | 2 [1-3] | 10 | Relapse-free survival based on the period of time until the first relapse Probability of progression-free survival based on the time until the progression to FRNS, SDNS or SRN Relapse rate | 2 [1-3] 2 [1-3] 2 [1-3] |
HCPs | 5 | 2 [1-3] | 5 | Probability of progression-free survival based on the time until the progression to FRNS, SDNS or SRN | 1 [1-3] | ||
Patients | 5 | 1 [1-3] | 5 | Relapse-free survival based on the period of time until the first relapse | 1 [1-3] | ||
Trial 10 | The change in UACR from baseline to the end of treatment | 10 | 10 | 4 [2-9] | 7 | Proportion of participants in remission defined as a reversal of UACR to normoalbuminuria | 3 [1-8] |
HCPs | 5 | 4 [2-6] | 4 | Proportion of participants in remission defined as a reversal of UACR to normoalbuminuria Proportion of participants who sustained remission after treatment | 2 [1-8] 2 [1-5] | ||
Patients | 5 | 5 [2-9] | 3 | Plasma aldosterone concentration | 2 [2-7] | ||
Trial 11 | The change in log-transformed urine albumin-to-creatinine ratio from baseline to the end of treatment | 10 | 9 | 3.5 [1-8] | 9 | eGFR The remission rate from early-stage nephropathy to prenephropathy stage at the end of treatment | 2 [1-6] 2 [1-6] |
HCPs | 5 | 3 [1-4] | 5 | The progression rate from early-stage nephropathy to overt nephropathy during the treatment period | 2 [1-3] | ||
Patients | 5 | 5 [3-8] | 4 | eGFR | 1 [1-2] | ||
Trial 12 [**Primary outcome match**] | Percentage of patients with treatment success | 10 | 5 | 1 [1-5] | 10 | Percentage of patients with treatment success | 1 [1-5] |
HCPs | 5 | 1 [1-5] | 5 | Percentage of patients with treatment success | 1 [1-5] | ||
Patients | 5 | 1 [1-5] | 5 | Percentage of patients with treatment success | |||
Trial 13 | Change in cGFR from baseline to month 12 | 10 | 7 | 3 [2-7] | 9 | Patient and graft survival | 1 [1-4] |
HCPs | 5 | 3 [2-3] | 5 | Patient and graft survival | 1 [1-1] | ||
Patients | 5 | 4 [3-7] | 4 | Incidence of AR | 1 [1-4] | ||
Trial 14 | The rate of haemodialysis independence at 3 months after randomization | 10 | 10 | 7 [1-10] | 3 | Overall survival | 1.5 [1-7] |
HCPs | 5 | 7 [1-8] | Overall survival | 1 [1-5] | |||
Patients | 5 | 8 [4-10] | Overall survival | 2 [1-7] | |||
Trial 15: primary 1 [**Primary outcome match**] | Loss of kidney function at 1 year | 12 | 2 | 1 [1-2] | 12 | Loss of kidney function at 1 year | 1 [1-2] |
HCPs | 5 | 1 [1-1] | 5 | Loss of kidney function at 1 year | 1 [1-1] | ||
Patients | 7 | 2 [1-2] | 7 | Acute kidney injury within 30 days of surgery | 1 [1-2] | ||
Trial 15: primary 2 | Acute kidney injury within 30 days of surgery | 12 | 2 | 2 [1-2] | 12 | Loss of kidney function at 1 year | 1 [1-2] |
HCPs | 5 | 2 [2-2] | 5 | Loss of kidney function at 1 year | 1 [1-1] | ||
Patients | 7 | 1 [1-2] | 7 | Acute kidney injury within 30 days of surgery | 1 [1-2] | ||
Trial 16 | eGFR over time | 12 | 8 | 3 [1-8] | 10 | Blood pressure control | 2.5 [1-8] |
HCPs | 5 | 4 [1-8] | 4 | Blood pressure control | 2 [1-3] | ||
Patients | 7 | 3 [1-8] | 6 | Early recognition and diagnosis of CKD | 2 [1-6] | ||
Trial 17 | Change from baseline to 24 weeks in UACR in the first morning urine sample | 11 | 8 | 4 [1-7] | 9 | Serum cystatin C-derived eGFR | 3 [1-8] |
HCPs | 5 | 1 [1-5] | 5 | Change from baseline to 24 weeks in UACR in the first morning urine sample | 1 [1-5] | ||
Patients | 6 | 4.5 [2-7] | 4 | 24-h total urine albumin excretion | 2.5 [1-4] | ||
Trial 18 | Relative change in serum phosphate concentrations from baseline to end of treatment | 12 | 3 | 1.5 [1-2] | 12 | Relative change in serum phosphate concentrations from baseline to end of treatment | 1.5 [1-2] |
HCPs | 5 | 1 [1-2] | 5 | Relative change in serum phosphate concentrations from baseline to end of treatment | 1 [1-2] | ||
Patients | 7 | 2 [1-2] | 7 | Changes in corrected PTH concentrations from baseline to end of treatment Relative change in serum phosphate concentrations from baseline to end of treatment | 2 [1-3] 2 [1-2] | ||
Trial 19 | Mean change in Hgb from baseline to end of treatment | 12 | 4 | 1.5 [1-4] | 12 | Mean change in Hgb from baseline to end of treatment | 1.5 [1-4] |
HCPs | 5 | 1 [1-1] | 5 | Mean change in Hgb from baseline to end of treatment | 1 [1-1] | ||
Patients | 7 | 3 [1-4] | 7 | Mean intradialytic change from pre-haemodialysis to post-haemodialysis in serum iron, unsaturated iron-binding capacity (UIBC) and TSAT Mean change in Hgb from baseline every 4 weeks | 2 [1-4] 2 [1-4] | ||
Trial 20 | Measured GFR at 12 months | 9 | 10 | 4 [1-9] | 6 | Rate of change of eGFR calculated from creatinine values at 0, 1, 3, 6, 9 and 12 months | 1 [1-5] |
HCPs | 5 | 4 [1-9] | 4 | Rate of change of eGFR calculated from creatinine values at 0, 1, 3, 6, 9 and 12 months | 2 [1-5] | ||
Patients | 4 | 5 [3-9] | 2 | Rate of change of eGFR calculated from creatinine values at 0, 1, 3, 6, 9 and 12 months | 1 [1-1] | ||
Trial 21 | Left ventricular mass index | 9 | 10 | 5 [1-7] | 5 | All-cause mortality and hospitalization for CV events | 1 [1-2] |
HCPs | 5 [4-7] | 3 | All-cause mortality and hospitalization for CV events | 1 [1-2] | |||
Patients | 5 [1-7] | 2 | 1) 2) All-cause mortality and hospitalization for CV events Exercise capacity: New York Heart Association functional class, 6-min walk test | 2 [1-2] 2 [1-7] | |||
Trial 22 | Percentage of subjects achieving an increase in Hb of ≥ 1.0 g/dL at any study point between baseline and End of Study or introduction or dose increase of ESA, blood transfusion or use of iron outside of protocol | 9 | 5 | 3 [2-5] | 5 | 1) 2) Mean change in Hb from baseline to end of week 6 (day 42) and end of week 8 (day 56)/end of study Percent of subjects achieving a clinical response | 2 [1-5] 2 [1-5] |
HCPs | 5 | 3 [2-4] | 5 | Percent of subjects achieving a clinical response | 1 [1-3] | ||
Patients | 4 | 3.5 [3-5] | 4 | Mean change from baseline to highest Hb | 1 [1-4] | ||
Trial 23 | Rate of s-K + decline in the first 48 h, using all post-baseline s-K + data | 9 | 5 | 2 [1-3] | 9 | Rate of s-K + decline in the first 48 h, using all postbaseline s-K + data Kidney function parameters | 2 [1-3] 2 [1-4] |
HCPs | 5 | 2 [1-3] | 5 | Rate of s-K + decline in the first 48 h, using all postbaseline s-K + data Changes in s-K + at various time points after start of treatment | 2 [1-3] 2 [1-3] | ||
Patients | 4 | 3 [2-3] | 4 | Kidney function parameters | 1 [1-1] | ||
Trial 24 | Proportion of CRR (complete renal remission) at 24 weeks | 9 | 2 | 2 [1-2] | 9 | CRR rate at 48 weeks | 1 [1-2] |
HCPs | 5 | 2 [1-2] | 5 | CRR rate at 48 weeks | 1 [1-2] | ||
Patients | 4 | 1 [1-2] | 4 | Proportion of CRR (complete renal remission) at 24 weeks | 1 [1-2] |
Discussion
The treatment choices of patients and clinicians should ideally be informed by evidence that interventions improve patient-relevant outcomes. Too often, medical research falls short of this modest ideal [3].
Strengths and limitations
Implications for practice
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Trialists must consult with patients and healthcare professionals to identify the outcomes they will need to inform their future decisions about the usefulness of the intervention being tested. Trialists should ask them to rank these outcomes to avoid choosing the wrong primary outcome. Trialists should then resist requests to add to the outcome list without having a compelling reason for collecting data not essential to stakeholders’ future treatment decisions. Where a core outcome set [5] exists, trialists should use it.
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Understanding the outcomes presented in our selection of trials was sometimes hard not only for patients but for healthcare professionals with many years of experience. Trial teams should make sure their outcomes make sense to those expected to use them.
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Telling potential participants what the primary outcome is in participant information leaflets and trial recruitment discussions would help them to make better decisions as to whether the trial was measuring something they consider important and, therefore, whether the trial was something they should give their time to.
Implications for future research
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It would be worth replicating our work in a few other clinical areas to see to what extent our findings are limited to breast cancer and nephrology or whether this represents a general problem. We think there is a general problem but knowing would be better than thinking. Replications would benefit from better trial descriptions than the very short ones we used in this study and from involving public contributors in writing outcome definitions. Having a researcher present to answer questions participants may have (as in our nephrology study) would be beneficial too.
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It would be worth exploring whether the situation is different for commissioned trials that give a primary outcome based on, for example, a James Lind Alliance Priority Setting Partnership (https://www.jla.nihr.ac.uk/about-the-james-lind-alliance/about-psps.htm) that has already involved consultation with stakeholders.