CLINICAL TRIAL MANAGEMENT

A clinical trial is the application of the scientific method to human health. Since such trials
require 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 the
trial, the proper management of clinical trials is crucial.

Contents
 1 Recruitment
 2 Public-private partnership
 3 Study designs and methods
 4 Risk management
 5 Risk distribution
 6 Key tasks and external agencies
 7 See also
 8 References

Recruitment

Over the last ten years, getting patients and doctors into clinical trials has become the most
delay-ridden aspect of the drug discovery and development process. When implemented
effectively, clinical trial recruitment (CTR) initiatives can be highly successful. Time lines can
be dramatically reduced and recruitment targets can be met ahead of schedule; every day
saved 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.
Considerable ethical scrutiny is applied to all patient recruitment materials and initiatives. For
example, in 2002 the European Commission issued guidelines for consultation which require
patient advertising and details of recruitment initiatives to be submitted to appropriate ethics
committees. Unfortunately, there is no simple code of established practice, no unified
regulatory 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 investigating
doctors, for example, question the need for extra activities as, they claim, there are sufficient
numbers of suitable patients among those already attending their clinics. However, practical
experience has shown that this is an over-estimation of the number of patients that physicians
will be able to recruit and it is estimated that only about 10% of a physician’s patients will
actually wish to enroll in a clinical trial.
Perhaps more importantly, there are also objections raised from within the industry. These
usually centre on a highly cautious approach to the ethics and legitimacy of patient-facing
initiatives. Some nervousness is understandable given the strict controls that govern DTC
marketing but for clinical research there is a critical need for increased patient understanding
and education. The signs are that the caution of the industry is slowly giving way to a new
openness and confidence.
A review of recent press coverage also highlights a deep skepticism of industry involvement
in clinical research. If not approached ethically, a firm’s CTR campaign can leave them wide
open to aggressive media criticism and adverse advocacy relationships. The key point to
remember is that the objective of all this work is ultimately to improve care for the patient. A
strenuous 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 clinical
research receives more and more active support of government bodies, advocacy groups,
charities and patient groups. This provides a collaborative environment and ensures that there
is always an independent counterpoint when the integrity of industry-sponsored studies is
attacked.
The American public sees a vast amount of government-sponsored education, designed to
maximize 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 a
300-page book on informed consent for patients.
Additionally, patient groups and organizations have formed new initiatives to increase
education about and participation in clinical trials for specific diseases. For example, people
with Parkinson’s disease can use PDtrials to find up-to-date information on Parkinson’s trials
currently enrolling participants in the U.S. and Canada and search for specific Parkinson’s
trials using criteria such as location, trial type, and symptom.[1] Other disease-specific services
exist for recruiting patients with other conditions as well.
Public-private partnership
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 are
demystifying clinical trials and generating considerable goodwill toward industry-driven
research.
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 $6
million fund, which the contributing pharma companies and National Cancer Institute will use
to 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 all clinical
protocols have at least one amendment during the study. The reasons appear to cover the full
range, from reliance on well-established designs without allowing newer, more creative ideas
to be considered and, at the other extreme, not testing new methods for the current application.
For example, in a recent anginastudy, treadmill exercise testing was used as the primary
efficacy 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 sufficient electrocardiogram (ECG) changes to qualify
for randomization. A quick pilot study would have alerted the sponsors before committing to
major cost.

Risk management
All research and development must involve some risk. Some of the risks are typically
encountered in the main stages of a typical clinical trial. The basic risks that are associated
with clinical Trial are:
 Enrollment of the subject at the sites within the projected time line
 Failure of the molecule eg efficacy ,
 Safety of the subjects eg number of SAEs reported to the enrolled subjects(Since
DSMB analyse the trial data different time intervals during the study and if they find
any risk associated to the patients safety at any time the trial may be terminated.
Risk distribution
Delivering the results on time, to the required standard, may have a lower risk in phase I than
in later phases, mainly because subjects are healthy and not potentially complicated patients,
and thus, recruitment can be predicted with some confidence. However, first administration to
humans is something of a leap into the unknown, and safety problems are always to be
considered. What is possibly less obvious is the risk of any early-phase design errors to later
phases and to the whole drug project. Once phase III is imminent, perhaps there is a degree of
confidence emerging, as much more is known about the drug. The requirement for phase III,
therefore, may be seen as accumulating data to enable a product license application. In fact,
the great expansion of activity dictated by phase III studies introduces even more complexity
and a new set of risks. The application of the drug to a more realistic clinical setting means
that we will not necessarily by studying "clean" patients. Patients will often have other
diseases on top of that under study and will only be under observation for a small proportion
of the time. Attention to clinical protocol design, thus, is at least as critical as in phases I-II.
Key tasks and external agencies
The most common reason for late tasks and projects is that they are started late. Before
patients can be screened for entry, a well-established set of start-up tasks must be completed,
and of these, some are relatively easy to plan, and others are less predictable. Those relying on
internal agreements (e.g., drug supplies, protocol sign-off), can be expedited by instilling the
right culture of negotiation between departments and individuals. But what of the external
elements, particularly regulatory and ethics approvals? The former is, fortunately, reasonably
easy to plan, because, in most countries, there are clear limits to the time and effort required to
meet regulatory requirements. Much more difficult is the matter of approval of ethical
standards. Across the EU, as well as in Australia, Canada, and USA, ethics committees'
practices may vary enormously so that, when planning a multinational study, good local
knowledge is crucial. Even inside the borders of the same country or state there is often
inconsistency, especially since the demise of single central approval for multicenter
studies<noref>. Theoretically, local research ethics committees (IRBs) are expected to follow
Department of Health guidelines, but, if they choose not to do so, there is apparently no
redress, so one may be presented with unexpected delays in particular centers because of
widely varying IRBs' practices. There is a move toward rationalization in the form of a two-
level approval process. A central committee will review the study and, if approved, pass it on
to local committees for ratification. Within the U.S., the Institutional Review Board (IRB) has
clearly-defined responsibilities and reporting lines. In Australia, central approval is still
possible, and the ethics committee sees itself more as a partner in research than as a regulator;
a very rapid start-up of studies is possible.
(Source from Wilkipedia)