Aclinical trialis the application of thescientific methodto human health. Since such trialsrequire the use of human test subjects and can severely impact the well-being of the subjects,as well as treatments of other people and large amounts of capital for those performing thetrial, the proper
Over the last ten years, getting patients and doctors intoclinical trialshas become the mostdelay-ridden aspect of the drug discovery anddevelopmentprocess. When implementedeffectively,clinical trialrecruitment (CTR) initiatives can be highly successful. Time lines can be dramatically reduced and recruitment targets can be met ahead of schedule; every daysaved in the progression to marketing authorization can equate to millions of pounds made in patent-protected sales revenue.However, great care is needed in the development of a CTR program.Considerableethicalscrutiny is applied to all patient recruitment materials and initiatives. For example, in 2002 the European Commission issued guidelines for consultation which require patientadvertisingand details of recruitment initiatives to be submitted to appropriate ethicscommittees. Unfortunately, there is no simple code of established practice, no unifiedregulatory body and no recourse to appeal. If an ethics committee doesn't like what a CRO has planned, the CRO can't use it. In Europe, this aspect has yet to be effectively addressed.Enhancing CTR is obviously an area in which great caution is required. Some investigatingdoctors, for example, question the need for extra activities as, they claim, there are sufficientnumbers of suitable patients among those already attending their clinics. However, practicalexperience has shown that this is an over-estimation of the number of patients that physicianswill be able to recruit and it is estimated that only about 10% of a physician’s patients willactually wish to enroll in a clinical trial.Perhaps more importantly, there are also objections raised from within the industry. Theseusually centre on a highly cautious approach to the ethics and legitimacy of patient-facinginitiatives. Some nervousness is understandable given the strict controls that govern DTCmarketing but for clinical research there is a critical need for increased patient understandingand education. The signs are that the caution of the industry is slowly giving way to a newopenness and confidence.A review of recent press coverage also highlights a deep skepticism of industry involvementin clinical research. If not approached ethically, a firm’s CTR campaign can leave them wide
open to aggressivemediacriticism and adverse advocacy relationships. The key point toremember is that the objective of all this work is ultimately to improve care for the patient. Astrenuous effort to maintain this focus throughout clinical development will ultimately allow pharma companies to reap considerable rewards.Over the past several years these problems have been addressed in the US, where clinicalresearch receives more and more active support of government bodies, advocacy groups,charities and patient groups. This provides a collaborative environment and ensures that thereis always an independent counterpoint when the integrity of industry-sponsored studies isattacked.The American public sees a vast amount of government-sponsored education, designed tomaximize understanding of clinical trials. A quick look at Cancer.gov and ClinicalTrials.gov, both run by the National Institutes of Health, illustrates just how much work is being done.This in turn is supported by private efforts such as Centerwatch.com, which currently offers a300-page book oninformed consentfor patients.Additionally, patient groups and organizations have formed new initiatives to increaseeducation about and participation in clinical trials for specific diseases. For example, peoplewithParkinson’s diseasecan usePDtrialsto find up-to-date information on Parkinson’s trialscurrently enrolling participants in the U.S. and Canada and search for specific Parkinson’strials using criteria such as location, trial type, and symptom.
Other disease-specific servicesexist for recruiting patients with other conditions as well.
The nature of American healthcare provision no doubt motivates patients to seek free or subsidized medication, but the investment, approach and partnerships in the US aredemystifying clinical trials and generating considerable goodwill toward industry-drivenresearch.A recently announced US public-private partnership, designed to improve trial recruitment,demonstrates how support for industry research can be broadened. The initiative created a $6million fund, which the contributing pharma companies and National Cancer Institute will useto accelerate patient recruitment for Phase I and II cancer studies. Naturally, the credibility of the public bodies involved enhances the effectiveness of the scheme.
Study designs and methods
A common pitfall is insufficiently rigorous evaluation of study designs and methods. A "straw poll" during a clinical project management training course revealed that virtually allclinical protocolshave at least one amendment during the study. The reasons appear to cover the fullrange, from reliance on well-established designs without allowing newer, more creative ideasto be considered and, at the other extreme, not testing new methods for the current application.For example, in a recentanginastudy, treadmill exercise testing was used as the primaryefficacy criterion. This is, of course, extremely well-validated methodology, but, in this case,the patients were elderly, so the exercise protocol was substantially modified to reduce the physical demand. The problem was that with such a mild exercise protocol, less than half the patients recruited showed sufficientelectrocardiogram(ECG) changes to qualifyfor randomization. A quick pilot study would have alerted the sponsors before committing tomajor cost.