PLoS ONE: Empty Reviews: A Description and Consideration of Cochrane Systematic Reviews with No Included Studies - your opinions?

Blogger's Note/Opinion: gyn cancers - this topic of discussion should be of interest: Cochrane total gyn cancers reviews = #85; empty reviews = #7; because Cochrane synthesizes and analyses systematic reviews,  often the results are inadequate (for patients/providers) in that studies included are: poor quality; lacking in data or are not randomized clinical trials; we often see this as 'further research is required'; many 'argue' that the value of systematic reviews in gyn cancers are dated (as discussed in this article) but part of this issue is the nature of, in particular, ovarian cancer research itself; the other 'issue' for this blogger is the number of systematic reviews which  continually review reviews; (re: reviews that include Cochrane systematic reviews); there needs to be a streamlining of systematic reviews (randomized clinical trial reviews) nominating or permitting one entity/conglomerate - eg. the philosophy of meaningful use, however, therein lies system wide issues within cancer; observational studies are often not included in the reviews and Cochrane is attempting to address this issue within the parameters of the purpose and philosophy of Cochrane itself, still for quality evidence Cochrane remains the leader; note also that Cochrane has always been one of, if not the leader, in including patients/consumers - your thoughts?

PLoS ONE: Empty Reviews: A Description and Consideration of Cochrane Systematic Reviews with No Included Studies

Introduction  

The Cochrane Library is the largest and perhaps best recognized global collection of health care evidence, currently hosting more than 4,500 systematic reviews in its Cochrane Database of Systematic Reviews (CDSR). However, it has been reported that clinicians find Cochrane reviews of limited relevance to practice decisions. For example, one study found that while Cochrane reviews are highly regarded for their quality, they are used less than other sources for clinical decision-making because of their emphasis on methodology and rigor rather than on clinical relevance [1].

It is not Cochrane's policy to provide guidelines for practice or policy decisions [2]. Instead, it sees itself as the provider of best quality evidence and specifically states that guidelines go “beyond a systematic review and require additional information and informed judgments that are typically the domain of clinical practice guideline developers.”
Systematic reviews that find no studies eligible for inclusion, commonly known as “empty reviews,” may be especially problematic for clinicians and other decision-makers. Little is known about the incidence, prevalence or variation in reporting of such reviews [3]. The little that has been written about them suggests that the reporting of implications for practice may sustain a risk for bias. With no studies meeting criteria for inclusion, these empty reviews may appear to: (1) offer no conclusions, (2) offer conclusions based on referenced excluded studies, (3) offer conclusions based on other evidence, or (4) offer conclusions not based on evidence. Thus, empty reviews may contribute to what appears to be generalized disappointment with The CDSR among some clinicians and policymakers [1], [4]........

Conclusions

The stated purpose of Cochrane reviews is to help healthcare providers, consumers, researchers, and policy makers “make well-informed decisions about health care… by providing a reliable synthesis of the available evidence on a given topic… considering all the evidence on the effect of an intervention” [2]......

Cochrane: YourHealthNet - navigating effective treatments with systematic reviews

YourHealthNet - navigating effective treatments with systematic reviews

The parts of a Cochrane systematic review and the information they contain - learning to navigate a review

Cochrane systematic reviews

Cochrane systematic reviews are the major output of the international organisation The Cochrane Collaboration, and over 4,000 Cochrane reviews are available online on The Cochrane Library. Because Cochrane review authors carry out their research with scientific rigour and follow detailed guidelines Cochrane reviews are considered a high quality source of research evidence.

David Tovey from The Cochrane Collaboration talks about systematic reviews.   » Read a transcript or » Listen to David's comments » See screen shot... This is how a systematic review looks on The Cochrane Library.

Explore the parts of a Cochrane systematic review

Systematic reviews are a complex mix of process and product - they report on the process review authors undertook, and the conclusions authors came to about what they found. All Cochrane systematic reviews follow the same format and methods; they have the same content in the same sections. This ensures their transparency and rigour.....

abstract: Cochrane Review: Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer

Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer [Cochrane Database Syst Rev. 2012] - PubMed - NCBI

Cochrane Database Syst Rev. 2012 Mar 14;3:CD004706.

Abstract

BACKGROUND:

Epithelial ovarian cancer is diagnosed in 4500 women in the UK each year of whom 1700 will ultimately die of their disease.Of all cases 10% to 15% are diagnosed early when there is still a good possibility of cure. The treatment of early stage disease involves surgery to remove disease often followed by chemotherapy. The largest clinical trials of this adjuvant therapy show an overall survival (OS) advantage with adjuvant platinum-based chemotherapy but the precise role of this treatment in subgroups of women with differing prognoses needs to be defined.

OBJECTIVES:

To systematically review the evidence for adjuvant chemotherapy in early stage epithelial ovarian cancer to determine firstly whether there is a survival advantage of this treatment over the policy of observation following surgery with chemotherapy reserved for treatment of disease recurrence, and secondly to determine if clinical subgroups of differing prognosis based on histological sub-type, or completeness of surgical staging, have more or less to gain from chemotherapy following initial surgery.

SEARCH METHODS:

We performed an electronic search using the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 3), MEDLINE (1948 to Aug week 5, 2011) and EMBASE (1980 to week 36, 2011). We developed the search strategy using free-text and medical subject headings (MESH).

SELECTION CRITERIA:

We selected randomised clinical trials that met the inclusion criteria set out based on the populations, interventions, comparisons and outcome measures.

DATA COLLECTION AND ANALYSIS:

Two review authors independently extracted data and assessed trial quality. Disagreements were resolved by discussion with a third review author. We performed random-effects meta-analyses and subgroup analyses.

MAIN RESULTS:

Five randomised controlled trials (RCTs), enrolling 1277 women, with a median follow-up of 46 to 121 months, met the inclusion criteria. Four trials were included in the meta-analyses and we considered them to be at a low risk of bias. Meta-analysis of five-year data from three trials indicated that women who received adjuvant platinum-based chemotherapy had better overall survival (OS) than those who did not (1008 women; hazard ratio (HR) 0.71; 95% confidence interval (CI) 0.53 to 0.93). Likewise, meta-analysis of five-year data from four trials indicated that women who received adjuvant chemotherapy had better progression-free survival (PFS) than those who did not (1170 women; HR 0.67; 95% CI 0.53 to 0.84). The trials included in these meta-analyses gave consistent estimates of the effects of chemotherapy. In addition, these findings were robust over time (10-year PFS: two trials, 925 women; HR 0.67; 95% CI 0.54 to 0.84).

Subgroup analysis suggested that women who had optimal surgical staging of their disease were unlikely to benefit from adjuvant chemotherapy (HR for OS 1.22; 95% CI 0.63 to 2.37; two trials, 234 women) whereas those who had sub-optimal staging did (HR for OS 0.63; 95% CI 0.46 to 0.85; two trials, 772 women).

One trial showed a benefit from adjuvant chemotherapy among women at high risk (HR for OS 0.48; 95% CI 0.32 to 0.72) but not among those at low/medium risk (HR for OS 0.95; 95% CI 0.54 to 1.66). However, these subgroup findings could be due to chance and should be interpreted with caution.

AUTHORS' CONCLUSIONS:

Adjuvant platinum-based chemotherapy is effective in prolonging the survival of the majority of patients who are assessed as having early (FIGO stage I/IIa) epithelial ovarian cancer. However, it may be withheld from women in whom there is well-differentiated encapsulated unilateral disease (stage 1a grade 1) or those with comprehensively staged Ib, well or moderately differentiated (grade 1/2) disease. 

Others with unstaged early disease or those with poorly differentiated tumours should be offered chemotherapy. A pragmatic approach may be necessary in clinical settings where optimal staging is not normally performed/achieved. In such settings, adjuvant chemotherapy may be withheld from those with encapsulated stage Ia grade 1 serous and endometrioid carcinoma and offered to all others with early stage disease.

Cochrane Review: abstract - Robotic assisted surgery for gynaecological cancer.

Abstract

BACKGROUND:

Robotic surgery is the latest innovation in the field of minimally invasive surgery. Robotic surgical systems have been used to perform surgery for endometrial, cervical cancer and ovarian cancer. There is mounting evidence which demonstrates the feasibility and safety of robotic surgery for gynaecological oncology.

OBJECTIVES:

To evaluate the evidence for and against robotic assisted surgery in gynaecological cancer.
MAIN RESULTS:
No studies were found that met the inclusion criteria. Controlled clinical trials (CCTs) are summarised and analysed, but are not discussed in the main body of the review as they present a high risk of bias.

AUTHORS' CONCLUSIONS:

Well-designed RCTs are required as only low quality evidence from CCTs is available. These studies support the use of robotic assisted surgery for endometrial cancer and cervical cancer, but these findings present a high risk of bias.

Cochrane Summaries website wins plain language award | The Cochrane Collaboration

Cochrane Summaries website wins plain language award

Only recently launched, the Cochrane Summaries website (summaries.cochrane.org) has received global attention, which reached a pinnacle when The Cochrane Collaboration was awarded the runner-up trophy for the best public website by the Plain English Campaign, which has been “fighting for crystal-clear communication since 1979.” David Tovey, the Editor in Chief of the Cochrane Library, explains that "The Cochrane Summaries website aims to deliver the credible, accessible, and impartial information that patients and carers need to improve understanding and promote shared decision making."...

Cochrane Evidence Updates - Antiemetics: American Society of Clinical Oncology clinical practice guideline update

Clinicians underestimate the incidence of nausea, which is not as well controlled as emesis (vomiting).

Cochrane Evidence Updates - Information interventions for orienting patients and their carers to cancer care facilities (including professional commentaries)

AUTHORS' CONCLUSIONS:
This review has demonstrated the feasibility and some potential benefits of orientation interventions. There was a low level of evidence suggesting that orientation interventions can reduce distress in patients. However, most of the other outcomes remain inconclusive (patient knowledge recall/ satisfaction). The majority of studies were subject to high risk of bias, and were likely to be insufficiently powered. Further well conducted and powered RCTs are required to provide evidence for determining the most appropriate intensity, nature, mode and resources for such interventions. Patient and carer-focused outcomes should be included.

abstract: Cochrane review - Optimal primary surgical treatment for advanced epithelial ovarian cancer

Abstract

BACKGROUND:

Ovarian cancer is the sixth most common cancer among women. In addition to diagnosis and staging, primary surgery is performed to achieve optimal cytoreduction (surgical efforts aimed at removing the bulk of the tumour) as the amount of residual tumour is one of the most important prognostic factors for survival of women with epithelial ovarian cancer. An optimal outcome of cytoreductive surgery remains a subject of controversy to many practising gynae-oncologists. The Gynaecologic Oncology group (GOG) currently defines 'optimal' as having residual tumour nodules each measuring 1 cm or less in maximum diameter, with complete cytoreduction (microscopic disease) being the ideal surgical outcome. Although the size of residual tumour masses after surgery has been shown to be an important prognostic factor for advanced ovarian cancer, it is unclear whether it is the surgical procedure that is directly responsible for the superior outcome that is associated with less residual disease.

OBJECTIVES:

To evaluate the effectiveness and safety of optimal primary cytoreductive surgery for women with surgically staged advanced epithelial ovarian cancer (stages III and IV).To assess the impact of various residual tumour sizes, over a range between zero and 2 cm, on overall survival.

MAIN RESULTS:

There were no RCTs or prospective non-RCTs identified that were designed to evaluate the effectiveness of surgery when performed as a primary procedure in advanced stage ovarian cancer.We found 11 retrospective studies that included a multivariate analysis that met our inclusion criteria. Analyses showed the prognostic importance of complete cytoreduction, where the residual disease was microscopic that is no visible disease, as overall (OS) and progression-free survival (PFS) were significantly prolonged in these groups of women. PFS was not reported in all of the studies but was sufficiently documented to allow firm conclusions to be drawn.When we compared suboptimal (> 1 cm) versus optimal (< 1 cm) cytoreduction the survival estimates were attenuated but remained statistically significant in favour of the lower volume disease group There was no significant difference in OS and only a borderline difference in PFS when residual disease of > 2 cm and < 2 cm were compared (hazard ratio (HR) 1.65, 95% CI 0.82 to 3.31; and HR 1.27, 95% CI 1.00 to 1.61, P = 0.05 for OS and PFS respectively).There was a high risk of bias due to the retrospective nature of these studies where, despite statistical adjustment for important prognostic factors, selection bias was still likely to be of particular concern. Adverse events, quality of life (QoL) and cost-effectiveness were not reported by treatment arm or to a satisfactory level in any of the studies.

AUTHORS' CONCLUSIONS:

During primary surgery for advanced stage epithelial ovarian cancer all attempts should be made to achieve complete cytoreduction. When this is not achievable, the surgical goal should be optimal (< 1 cm) residual disease. Due to the high risk of bias in the current evidence, randomised controlled trials should be performed to determine whether it is the surgical intervention or patient-related and disease-related factors that are associated with the improved survival in these groups of women. The findings of this review that women with residual disease < 1 cm still do better than women with residual disease > 1 cm should prompt the surgical community to retain this category and consider re-defining it as 'near optimal' cytoreduction, reserving the term 'suboptimal' cytoreduction to cases where the residual disease is > 1 cm (optimal/near optimal/suboptimal instead of complete/optimal/suboptima

Glossary | The Cochrane Collaboration (worth bookmarking)

examples:

Adverse effect search for term

An adverse event for which the causal relation between the drug/intervention and the event is at least a reasonable possibility. The term ‘adverse effect’ applies to all interventions, while ‘adverse drug reaction’ (ADR) is used only with drugs. In the case of drugs an adverse effect tends to be seen from the point of view of the drug and an adverse reaction is seen from the point of view of the patient.See also: Adverse event, Side effect Also called: Adverse reaction

Baseline characteristics search for term

Values of demographic, clinical and other variables collected for each participant at the beginning of a trial, before the intervention is administered.

Causal effect search for term

An association between two characteristics that can be demonstrated to be due to cause and effect, i.e. a change in one causes the change in the other. Causality can be demonstrated by experimental studies such as controlled trials (for example, that an experimental intervention causes a reduction in mortality). However, causality can often not be determined from an observational study.

blog: Does Cochrane have a plan for consumer participation? | Cochrane Consumer Network

Cochrane Collaboration Review:Evaluation of follow-up strategies for patients with epithelial ovarian cancer following completion of primary treatment

Plain language summary

Evaluation of follow-up strategies for patients with epithelial ovarian cancer following completion of primary treatment

Ovarian cancer is the sixth most common cancer and seventh commonest cause of cancer death in women worldwide. Traditionally, many patients who have been treated for cancer undergo long-term follow up in hospitals. Whilst there may be other benefits from follow up, it has been suggested that the use of routine review may not result in women with this disease living longer given that recurrent ovarian cancer is incurable.

We set out to review the evidence for different types of follow up of women who have completed treatment for the commonest type (epithelial, that is coming from the surface of the ovary) of ovarian cancer. Only one good quality  (blogger's note: Rustin trial) randomised (toss of a coin to choose which group) trial was found which could give any evidence on what to do. This trial suggested no increase in length of life from early treatment with chemotherapy for women with recurrence that was identified by a tumour marker (CA125) blood test compared to waiting to give treatment when women developed symptoms from their cancer.

We conclude that the very limited evidence suggests that there may be no benefit from early detection by the blood test and subsequent early chemotherapy for recurrent ovarian cancer. Also, the women having early chemotherapy treatment of their relapsed cancer may have led to a decreased quality of life for these women compared to the group who were treated when they noticed symptoms.

Randomised controlled trials are needed to compare different types of follow up, looking at quality of life and anxiety outcomes. If new treatments become available for relapsed ovarian cancer, the methods of follow up may need re-assessing to see if earlier intervention improves survival or other outcomes.

abstract - Cochrane Review: Selenium for preventing cancer

Selenium for preventing cancer

Selenium is a trace element that is important for human health, but might also be harmful for humans when the taken in excess.
Fifty-five studies with more than one million participants were included in this systematic review. Forty-nine studies observed and analysed whether healthy people with high selenium levels in blood or toenail samples or with a high selenium intake developed cancer more or less often than other people. We found that people with higher selenium levels or intake had a lower frequency of certain cancers (such as bladder or prostate cancer) but no difference for other cancers such as breast cancer.

However, it was not possible to determine from these studies that selenium levels or selenium intake were really the reason for the lower risk of cancer in some people. Factors apart from higher selenium levels could also influence the cancer risk: They might have had a healthier nutritional intake or lifestyle, have had a more favourable job or overall living conditions.

Six randomised controlled trials (RCTs) assessed whether the use of selenium supplements might prevent cancer. In general, there are two types of selenium supplements: one type uses the salt of selenium as main ingredient, the other type uses organic selenium. These two types may act differently in the human body when ingested. We assessed the quality of each trial according to four established methodological criteria. The trials with the most reliable results found that organic selenium did not prevent prostate cancer in men and increased the risk of non-melanoma skin cancer in women and men. Other trials found that participants using selenium salt or organic supplements had a decrease in liver cancer cases. However, due to methodological shortcomings this evidence was less convincing. We advise further investigation of selenium for liver cancer prevention before translating results into public health recommendations. We also recommend that there should be further evaluation of the effects of selenium supplements in populations according to their nutritional status as they may differ between undernourished and adequately nourished groups of people.

To maintain or improve health, access to healthy food and a healthy diet is important. Currently, there is no convincing evidence that individuals, particularly those who are adequately nourished, will benefit from selenium supplementation with regard to their cancer risk.

EvidenceUpdates: Interventions to enhance return-to-work for cancer patients. Cochrane Database Systematic Rev. 2011

Cancer survivors are 1.4 times more likely to be unemployed than healthy people. It is therefore important to provide cancer patients with programmes to support the return-to-work process.

OBJECTIVES: To evaluate the effectiveness of interventions aimed at enhancing return-to-work in cancer patients.

link - updated Comments from Clinical Raters

Cochrane Review: abstract - Chemotherapy for malignant germ cell ovarian cancer [Cochrane Database Syst Rev. 2011] - PubMed result

AUTHORS' CONCLUSIONS:
We found only low quality evidence on the use of chemotherapy in malignant germ cell tumours of the ovaries. Therefore we are unable to reach definite conclusions about the relative benefits and harms of chemotherapy use in this disease regardless of disease stage. Due to the benefit of chemotherapy in germ cell cancer of the testis, a trial of chemotherapy versus best supportive care is unlikely to be feasible. Despite this, good quality randomised studies are warranted in this disease to define the role of chemotherapy (type of chemotherapy, duration of treatment, benefit, short and long term toxicities). Given the rarity of this disease, we feel a trans-global approach would be essential in order to perform such trials.

alternate source including professional commentary (gynecologic oncology) link

Guest post: Absolute risk not as straightforward as you might think - Gary Schwitzer's HealthNewsReview Blog

"...As a Cochrane review pointed out this week (Persuasive health information could be misleading)  (note - this link forwards to a Reuters story) relative risks are very persuasive, but they don't always serve your best interests when making health decisions....:

call for papers: Measuring Consumer Involvement in Health and Social Care: Dividing fact from fiction | Cochrane Consumer Network

Cochrane CAM Reviews Commentary: Is There More to Quality Than the Research Method Itself?

Depression and anxiety in people with physical illness - Special Collection - The Cochrane Library (includes references to the Cochrane Gyn Group/research papers)

Editorial :: The role of Cochrane Review authors in exposing research and publication misconduct - The Cochrane Library

Note: while important the real question is the root of the problem - cause

"At the Joint Colloquium of the Cochrane & Campbell Collaborations in Keystone in October 2010, we ran a workshop about the problems of detecting research misconduct,[1] and had a wonderful discussion with participants. The US Office of Research Integrity defines research misconduct as: "fabrication, falsification, or plagiarism in proposing, performing, or reviewing research, or in reporting research results; fabrication is making up data or results and recording or reporting them; falsification is manipulating research materials, equipment, or processes, or changing or omitting data or results such that the research is not accurately represented in the research record; plagiarism is the appropriation of another person's ideas, processes, results, or words without giving appropriate credit; research misconduct does not include honest error or differences of opinion".[2] The Committee on Publication Ethics (COPE) also outlines publication and research misconduct in its flowcharts for editors, and highlights redundant (duplicate) publication, changes in authorship, undisclosed conflicts of interest, and ethical problems as additional types of misconduct.[3] Cochrane Review authors, as they analyse the entirety of primary research evidence in a specific area, are well placed to identify many of these types of research and publication misconduct. Indeed, Professor Sir Iain Chalmers urged systematic reviewers, not so long ago, to harness their unique opportunity to detect plagiarism.[4].....cont'd

2011 Cochrane Review: Maintenance chemotherapy for ovarian cancer