There are many terms used to describe the design of clinical trials. There are efforts to reduce inadequate reporting in clinical trial reports and increase transparency thus aiding interpretation, for example the CONSORT Group. Some of the terms used are as follows.
Study design:
- Superiority study - aims to demonstrate that one treatment is better than another active treatment or a placebo.
- Non-inferiority study - aims to demonstrate that one treatment is not worse than another active treatment within a defined acceptable level of clinical inferiority.
- Equivalence study - aims to demonstrate that two interventions are equivalent to each other within a defined acceptable level of clinical difference.
Study methodology:
- Observational - the study watches what happens rather than directly offering interventions.
- Experimental - the study actively provides an intervention, typically this is a randomised controlled trial.
- Randomisation - participants in the study are randomly assigned to treatment groups rather than being selected. This helps to reduce selection bias.
- Retrospective - looks at events that have already happened. This method usually employs healthcare system databases.
- Prospective - looks at what happens to patient populations as time passes.
Level of 'Blinding':
- Open - participants, the clinicians conducting the study and the study assessors all know which intervention group a patient is in.
- Single blind - the participants don't know which intervention group (treatment or placebo) they are in.
- Double blind - neither the participants nor the clinicians conducting the study know which intervention group individual patients are in.
- Triple Blind - neither the participants, the clinicians conducting the study nor the study assessors know which intervention group individual patients are in.
Action: A better understanding of these terms will allow clinicians to interpret the relevance and impact of clinical studies.
Non sequitur, translated from Latin to English, means "it does not follow". Non sequiturs are often used in advertising both overtly and covertly.
An example of an overt use would be placing two statements next to each other so that the reader correlates the two statements despite no correlation existing. For example:
- Drug X exhibits high affinity for the target receptor
- Drug X has no known side effects
While these two statements may be factually correct they are not related to each other and there is no cause and effect. Despite this, on first reading, you may have been inclined to believe that Drug X had no side effects because it has a high affinity for the target receptor.
A more covert use of non sequiturs is to involve pictorial or graphical representations. For example, many adverts depict tropical or exotic locations or idealistic situations. These locations and situations often have no direct link with product being advertised.
Action: Clinicians should be aware of the potential influence of non sequiturs in advertising. Careful analysis of promotional materials will ensure that incorrect conclusions are not formed based on unrelated statements.
PLoS Medicine has published an article detailing many of the tricks of the trade used by pharmaceutical company sales representatives. A former pharmaceutical sales representative and a physician who researches pharmaceutical marketing wrote the article.
The article cites the US$4.8 billion investment made by pharmaceutical companies in 2000 in direct promotional activity to prescribers from an overall budget of US$15.7 billion for promoting all prescription drugs. It also provides an insight into the training these individuals undergo and some of the data they are trained to collect and report back to their respective companies. All of this activity is aimed at changing prescribing habits to favour the promoted drug.
Of particular interest is the table (Part 1 and Part 2) that categorises different types of clinicians and the techniques used to overcome the barriers to changing prescribing habits.
Clinicians may find it interesting to categorise themselves using the table and see if the marketing activity they encounter is being tailored to them. Learning how promotional activity works will allow clinicians to recognise and counter these tactics.
In conclusion the article points out that while sales representatives appear friendly, charming and sympathetic all of this is carefully constructed to increase sales and market share for particular drugs. They recommend that clinicians find an unbiased source for information on drugs.
Action: Clinicians will have their own views on the benefits provided by sales representatives in terms of education, samples and service provision. It is important that all clinicians consider the potential for bias in any information provided during these encounters.
The British Medical Journal has published a systematic review that examined the use of composite end points in cardiovascular trials. The aim was to assess the importance to patients of each component in the composite end points and to examine the frequency of these events in the studies.
The study examined cardiovascular randomised controlled trials published in the 18 months from 1st January 2002 in six medical journals (Lancet, Annals of Internal Medicine, Circulation, European Heart Journal, JAMA and New England Journal of Medicine). The advantage of using composite endpoints is that trials can be smaller in terms of numbers of patients and duration. 114 trials were identified that used composite endpoints.
Only 68% of the studies reported full data for each of the composite end point components. Over half of the studies (56%) showed a high degree of variability of importance to patients in the composites. This is due to inclusion of outcomes that are very important to patients, for example cardiac death, in combination with outcomes that are insignificant to patients, for example doubling of serum creatinine concentration.
This analysis also found that the measures that were of least importance to patients contributed the most to the event rates and treatment effects. Removing these less important outcomes from the composite would mean fewer trials reached statistical significance.
It is clear from this review that when interpreting randomised controlled trials using composite endpoints, each of the components of a composite endpoint should be viewed separately. This will ensure that claims relating to outcomes of greatest importance to patients are not exaggerated.
For example, if a study was highly statistically significant on a composite endpoint of cardiovascular death, non-fatal MI and re-admission to hospital but had similar event rates for cardiovascular death and non-fatal MI with the significance being driven by a large difference in the rate of re-admission to hospital it would be important to ensure that the intervention was not interpreted as reducing deaths or non-fatal heart attacks.
Promotion of medicines relies heavily on data from clinical studies but many people want to know what others are doing before they will consider using a new product. To overcome this obstacle promotional activity will often seek to use opinion leaders.
Opinion Leaders are well-respected authorities in their area of expertise, whose name will be recognised and who are preferably working in the local area. This will include hospital consultants, medical directors and increasingly pharmaceutical advisors.
Adding the opinion leaders positive endorsement to the sales message bolsters the promotional message.
Critical Appraisal of this type of information is useful when considering the impact of the promotional message on current practice.
- Does the opinion leader provide care for or advice about patients who are similar to your own in terms of age, gender, ethnicity and social status
- Do your patients have the same disease and at the same severity to those seen by the opinion leader
- Can the endorsement of the opinion leader be substantiated, either at the time of the promotional activity or independently later
For example, I have recently been misquoted during promotional activity for a product undertaken in the PCT where I work. I have made a complaint through the normal channels and will post further details once the outcome is confirmed to me in writing.
