Aim

Manual for Handsearchers Cochrane Wounds Group Contents The Cochrane Collaboration Eligibility criteria & classification of Trials What is a Randomised Controlled Trial? Methods of allocation Other potentially useful trials What not to include Handsearching Guidelines Coding of Trials What to photocopy Checklist for journal handsearchers Journal search report Glossary of terms Page 3 4 5 6 7 9 11 14 15 16 17 18 2 The Cochrane Collaboration The Cochrane Collaboration is an international organization that aims to help people make well-informed decisions about healthcare by preparing, maintaining and promoting the accessibility of systematic reviews of the effects of health care interventions. It also aims to keep these reviews up to date as new evidence becomes available. To do this, reports of Randomised Controlled Trials (RCTs) are collected from books, journals and conference abstracts. These are found by thoroughly searching the medical literature both electronically and by hand. Reports of RCTs are: * sent out to reviewers so they can update reviews * added to the Wounds Group Specialized Register Aim of Handsearching The aim is to identify all RCTs and Systematic Reviews (SR's) in the medical literature. It is important not to exclude a study that may possibly be an RCT. 3 Eligibility Criteria and Classification of Trials What is an RCT? An RCT is a trial of any aspect of healthcare including screening, treatment, prevention etc, where the individuals (or other units) followed in the trial were definitely or possibly assigned prospectively to one of two (or more) alternative forms of health care using: Random allocation - where random means that the participants in the trial were assigned to different interventions by a chance process - they have equal chances of being in one group as in another. The units of randomisation may be individuals, groups (communities or hospitals), organs (eyes), or other parts of the body (legs, arms). Controlled Clinical Trial - CCT These are trials using some form of quasi-random allocation - such as date of birth or case record number. These studies do not use true randomisation but these they may be important and need to be recorded. 4 What is a Randomised Controlled Trial? One group of people Experimental Intervention Control Intervention Follow up Assessment (+/- blinding) Follow up Assessment (+/- blinding) 5 Examples of methods of allocation - as they may be described in the literature RCT  Patients were randomly allocated to the two treatment groups using a random numbers table  Patients were allocated to the test or control group using numbers in sealed envelopes  Patients were allocated to the test or control group by use of a random code CCT  Patients were allocated to the test or control groups by their NHS number - odd numbers were the control  Patients were allocated alternately to the the test or control group Allocation methods not stated  Patients admitted to the study were split into two groups  Patients were allocated to the test or control group  All patients were given either treatment tablets or placebo tablets of similar appearance 6 Other potentially useful trials Trials which mention double-blinding or masking where neither the participant or the assessor is aware of which groups they are in are almost always RCTs. An example of this is where a trial involves the use of a placebo. Cross over studies - where the first intervention may be randomized or quasi-randomized should be included Some studies may not even mention the word random so all prospective trials that mention a control group should be included. Articles or reports mentioning trials which are planned, ongoing incomplete or have been abandoned should be included Systematic Reviews should also be recorded as they are potentially useful sources of information about RCTs relevant to the subject area being reviewed 7 BEWARE: The term random selection does not necessarily mean random allocation - further evidence is needed Where random selection DOES NOT mean random allocation One group of people Sample of patients selected at random Treatment given Follow up Assessment What not to include Articles which state that they are:  historical control  population control  animal studies OR Descriptive studies  Correlation Studies - two variables are plotted to see if there is a pattern, for example, smoking patterns in population and rates of lung cancer. This is not experimental - nothing is being allocated.  Case Report/Series - people may be surveyed or given an intervention BUT there is no control group  Cross-section/ Prevalence Survey - this is a survey of a population. It is not experimental – no intervention is being allocated to the populations continued on following page… 9 OR Observational analytic studies  Cohort Studies - which are long follow up studies of treated and untreated groups. These are only of use if there is random allocation at the start.  Case Control Studies - two or more different populations are compared, for example, cases of hypertension and controls of healthy individuals. To confuse matters, sometimes the intervention for each group is randomised - this then makes it two different randomised controlled trials Only trials which involve living humans are included 10 Handsearching - Guidelines  It is useful to photocopy the table of contents as a checklist  The whole journal should be searched page by page in order to identify the maximum number of relevant reports Articles The layout of these is similar in many journals, in most cases there will be:  a title  an abstract or summary  an introduction/background  methods section  results  discussion  conclusion  acknowledgements  references You will rarely have to read the whole article  first look at the title - if it mentions randomised-controlled trial it should be photocopied. (See ‘What to Photocopy’)  if not - look at the abstract/summary and then the methods - if it is still not clear then continue to read until you are sure whether it meets the eligibility criteria or not  check the references at the end of the article - look for any mention of other RCTs Review articles  those describing RCTs or CCTs should be photocopied  also photocopy articles which are Systematic Reviews of the research evidence Letters  these may mention RCTs, CCTs or SRs - planned, complete or ongoing - if they do, photocopy the whole letter Abstracts  photocopy these if they meet the criteria Conference Proceedings  may also mention RCTs, CCTs or SRs and if so, should be photocopied Book Reviews  check for any mention of RCTs, CCTs or SRs (searching each journal issue should not take more than about 20 minutes some will take less time) If in doubt - photocopy. The quality of the study does not need to be judged at this stage. It is probably easier to mark each relevant page in each journal being searched and then do all the photocopying at once On the photocopy:  Highlight the evidence, i.e. where it states that this trial is, or may be an RCT or CCT.  Highlight the full citation, i.e. the journal name, year, month, volume, issue and page numbers - in most journals these are already printed on each page, if not, please add them 12  In the top right hand corner of the first page, indicate whether the trial is RCT, CCT or Systematic Review (SR). If you are not sure or it is not stated, classify this as SOS (‘second opinion sought’)  make sure photocopies are clear and readable 13 Coding of Trials    Randomised Controlled Trial RCT Quasi-randomised Controlled Trial CCT Possibly Randomised or Quasi-randomised Controlled Trial CCT   Systematic Review or Meta-analysis SR Second Opinion Sought SOS 14 What to photocopy The Wounds Group are developing a database of trials relevant to the group. The scope is as follows:  Pressure Sores - treatment & prevention  Leg Ulcers - to include venous ulcers, rheumatoid ulcers, diabetic foot ulcers  Burns  Traumatic Wounds  Malignant Wounds  Surgical Wounds  Skin Abscess  Bites (mammalian)  Scarring Studies pertaining to gastric or duodenal ulcers, corneal ulcers, sexually transmitted diseases, dental wounds, eye injuries are not within the scope of the Group.  If items are found which mention trials which are within the Wounds Group scope, the full article, letter, review etc, should be photocopied  If articles do not come within the Wounds Group scope, then the first page and the part of the article showing that it may be an RCT or CCT should be photocopied. Again, highlight the evidence and make sure the citation is complete.  If it is a letter, photocopy the whole letter.  If any of the references at the end of the article mention randomisedcontrolled trials but the article does not, then just photocopy the references, highlighting the relevant references. Then:  Fill in the Journal Search Report Sheet, remembering to include the month of the journal and also if there are missing journals or missing pages in the journal 15  Fill in the checklist so you know where you are up to with each journal  Send in the photocopies along with the Journal Search Report sheet 16 Checklist for journal handsearchers  photocopy the table of contents  examine each issue page by page to identify all reports of RCTs and CCTs and Systematic Reviews, remembering they may be in articles, letters, news columns, editorials, references, etc.  if the item is within the scope of the Wounds Group, photocopy the whole item, if not then just photocopy the first page  highlight the evidence - the key terms that show the item is an RCT, CCT or a possible RCT  ensure the full citation is available on all photocopies either highlight what is already printed or add to the copy  code each item as RCT, CCT, SR or SOS - in the right hand corner of the first page  complete the Journal Search Report Sheet - remembering to include the month and any missing journals or pages 17 Journal Search Report Form Searchers Name: Phone number: Journal Title: Year/Month: Issue: Classifications: Volume: Pages: enter the total number of trials or reviews found in the journal and supported by attaching the necessary photocopies Relevant to Wounds Group RCT CCT SR SOS Others Any comments from Searcher to Wounds Group: Any pages/parts missing from the Journal: Date search completed and returned to Wounds Group: 18 GLOSSARY – for reference Words or phrases marked by an * indicate that they are potentailly relevant trials. Types of trial and terms relating to trial design which you may find useful when reading the journal. Blinding In clinical trials this means that the patients and/or the investigators are not aware of which treatment the patient is getting. See double blind and single blind. Case (History) Study A report on one or more people, often with an unusual disease. Case-control Study (Also called case comparison study, case compare study, case history, case referent study, and retrospective study) Compares people with a disease (cases) with a group of people without the disease (controls). Examines possible causes or risk factors for the disease. Example: If you were interested in finding out whether thalidomide caused birth defects you could select a group of children with birth defects (cases) and a group of children without birth defects (controls). You could then find the number of children in each group that had been exposed to thalidomide through their mothers taking the tablets. This is sometimes called a retrospective study because it is looking back in time. Clinical Trial * (Also called therapeutic trial, intervention study). A trial which tests out a drug or treatment to see whether it is effective or safe. This general term encompasses randomised controlled trials, controlled clinical trials, randomised clinical trials, and other trials where there may or may not be a control group. Cohort Study This type of study takes a group of people and follows them up over a period of time to see who gets a disease or how a disease progresses. Example: If you were interested in risk factors for heart disease, you could follow a group of people without heart disease for several years. You could see which people developed disease and which people did not. 19 Control Has several meanings which can cause confusion: 1) In clinical trials comparing two or more treatments, control refers to the comparison group that receives one of the following: a) a placebo b) no treatment/care c) usual form of care/treatment (e.g. the normal surgical operation for a hip replacement, the normal exercise programme following a stroke) d) another drug / treatment. 2) In case-control studies, the control refers to the comparison group without the disease 3) In studies of infectious diseases, control means programmes aimed at eliminating the disease. Controlled Clinical Trial* Refers to a study that compares one or more treatment groups to one or more comparison (control) groups. Whilst not all controlled studies are randomised, all randomised trials are controlled. For the purposes of handsearching and coding, if there is doubt as to whether the patients were randomly allocated treatments, code as CCT Cross sectional Study This is like taking a 'snapshot' of a group of people at one point in time and seeing the prevalence of certain diseases, for example heart disease, in that population. You could also try to find out how many (for example) smoked, drank etc. Cross-over Trial Design* A method of comparing two or more interventions where subjects are randomly allocated to receive one intervention and subsequently receive the other(s). The order of the interventions is random. Example: If comparing aspirin with a placebo, half of the patients would be randomly allocated to receive aspirin first, followed by the placebo. The other half of the patients would receive a placebo first, followed by aspirin. Sometimes all patients receive a placebo, before they are randomly allocated to the treatments. See also washout period. Double blind Neither the patients nor the investigator are aware of the treatment the patient is being given. The purpose of this is to reduce bias. A double blind trial is a usually a randomised controlled trial or a controlled clinical trial. Epidemiology The study of the distribution and determinants of disease frequency in the population. Incidence This is the number of new cases of a disease in a population 20 Intervention Study* See Clinical Trial Parallel Group Trial Design* These trials compare two or more interventions with subjects allocated to one of the interventions only. Phase I / Phase II Studies These studies are concerned with drug safety, drug dosage and drug effectiveness. They are not normally randomised or controlled, and therefore not of interest to us. (However within a crossover trial the first period is sometimes referred to as Phase 1.) Placebo A harmless substance given as an alternative to the intervention e.g. a sugar pill. Should be identical to the intervention being tested i.e. the appearance, dosage, administration instructions should be identical to the active drug. Placebo effect Patients report a favourable response to any treatment regardless of whether it is the real thing, or a placebo. Prevalence study You are trying to find out how many people have a particular disease in the population. See prevalence and cross sectional study Prevalence This is the number of existing cases of a particular disease at any point in time. Prospective In clinical trials, this means that patients are divided into groups before treatment is given. That is, the investigators plan in advance what treatments are to be given. Subjects are then selected and treatments allocated, either randomly or non-randomly. Quasi-random Methods of allocating patients to a treatment which are not statistically random Quasi-random methods of allocation include: Date of birth Days of the week Medical record number Months of the year Order in which the patients are included in the study 21 Quasi-randomised Trial* A trial using a quasi-random method of allocating patients to different forms of care. For the purposes of handsearching and coding, code as CCT Random Governed by chance Random selection Random selection refers to how the group of patients was selected from a population. It is not related to how the patient was allocated a treatment. Random allocation / assignment / Randomisation/ Random assignment implies that each individual has the same chance of receiving each of the possible treatments. Also the probability that an individual will receive a particular treatment is independent of the probability that any other subject will receive the same treatment. Methods of randomisation include: Blocks of ten Coin tossing Deck of cards Codes Computer generated numbers / computerised /Minimisation Pre-ordered list Random number tables Remote randomisation Sealed envelopes Stratified randomisation See also quasi random Telephone randomisation Randomised Controlled Trial* A trial in which subjects are randomly allocated into groups, to receive, or not to receive a treatment. This treatment could be a drug, a surgical procedure, a dressing, a diet, an exercise programme etc. Can also compare two or more types of drug. See also Control For the purposes of handsearching and coding, code as RCT Randomised Clinical Trial* See randomised controlled trial Should be coded in the same way as a Randomised Controlled Trial Retrospective Looking back in time. In terms of collection of data, the treatment, or event has already happened. Example: A study may compare two different drugs for cancer, by examining the medical records of people who have had the two different treatments in the past. This 22 means that the patients cannot have been randomised to the two treatments because they were administered at the time when the investigation begins. Retrospective study See case-control study. Review This is an article that looks at a number of different studies and may draw conclusions about a particular treatment. The review may look at several randomised controlled trials and compare the results. It is not usually a randomised-controlled trial in itself. Occasionally the author may report methods and results of a trial that he/she is involved with. Risk Factor An aspect of a person's lifestyle or environment which increases the probability of occurrence of a disease. For example, cigarette smoking is a risk factor for lung cancer. Single Blind The investigator is aware of the treatment the patient is getting, but the patient is unaware. Therapeutic Trial See Clinical Trial* Washout period/phase The stage in a crossover trial when treatment is withdrawn so that patients body returns to normal. 23