Standard Operating Procedures (SOPs) are detailed, written instructions to achieve uniformity of the performance of a specific step in clinical study (see the step on 'Finalising SOPs' for more information).

There are a number of different approaches to developing SOPs depending on the complexity of task and the number of people involved in the development. It is important to ensure that the document is reader friendly by incorporating flow diagrams or a graphical representation of the steps to be followed. Annotated pictures also work well for people who are more pictorial in their learning and helps to understand more complex and detailed SOP.

Advantages of using SOPs during clinical research
- SOPs help to ensure a more practical and meaningful interpretation of GCP, and documents and enhances learning for the investigator and the study team.
- It demonstrates to sponsors, auditors and inspectors that the site is committed to implementing GCP.
- SOPs will reduce system variation, which is the enemy of efficiency and quality control.
- SOPs facilitate training since having complete step-by-step instructions helps trainers ensure nothing is missed and provides a reference resource for trainees.
- Well-written SOPs facilitate cross training. SOPs can be an excellent reference document on how a task should be performed by study staff filling in on jobs they do not perform on a regular basis.
- Study staff can coach and support each other if there is documentation available on exactly how various tasks must be done and everyone knows what the rest of the team are supposed to be doing. This can also help generate a more cooperative team approach to getting all the daily tasks done correctly, consistently.

SOPs should be easily assessable and updated at pre agreed intervals so that efficiencies identified with constant use can be incorporated in the document. It also allows redundant titles or roles to be updated.

SOP Training and implementation
People tend to be supportive of the things they help create. Involving study staff in developing SOPs can help assure the final product is more complete, useful and accepted. It is best practice to integrate SOPs into a comprehensive document management system and have original copies maintained in a secure location.
Expired original SOPs should be annotated as "Archived" and maintained so they can be retrieved for reference or inspection. To eliminate confusion, photocopies of expired SOPs are destroyed once a new version is effective. SOPs must be regularly reviewed and updated to accommodate changes in regulatory requirements. Any deviations should be documented and authorised but a continuous deviation from SOP could mean that the document may be ready for revision.
When using the same SOP in basic training, less detail may be desirable. The amount of detail should be tailored to the level of the training. For example, new trainees might be overwhelmed by large amounts of detail, so only the details they need to get the job done correctly should be appropriate. Similarly, the same SOP used as an on-the-job reminder should be an overview of the SOP.

For in-depth follow-up training or retraining, you may want the SOP to contain more details and background information explaining why certain things are done or the science behind certain practices.

Training will need to be consistently delivered to all team to ensure there is no misinterpretation of the SOPs. Training over the years has improved and can be taken in a number of ways such as classroom based training; computer based training or self reading. The choice of training will depend on the type of SOP and the structure of the institution.

Computer based training and self read training represents a cost effective way of training staff on SOPs and this method has widely been adopted by many research institutions. It offers the advantage of being able to train staff at multiple locations in a consistent and cost effective manner. The timing of delivery is very quick and can be tracked electronically with date and time stamp.

Computer based training can be used for more cumbersome SOPs or where staff need to be trained on new electronic systems. The training tends to include computer based test to assess users understanding of the SOP. One of the advantages of this training is that it doesn’t have to be completed all at once thereby offering some flexibility in training.

Classroom based training on the other hand are rigid and are becoming rare for the sole reason of the time, resources and cost required in delivering training. Often this type of training is conducted along with any other company training, such as staff induction.

As well as training staff on SOPs it is necessary to check compliance to the SOPs and it is important that users adhere to the relevant SOPs.
SOPs should be issued prior to their effective dates to allow sufficient time for training before they become effective. Training may be as simple as reading and understanding the SOP. Alternatively, training may take the form of group instruction/discussion, one-to-one instruction, e-module instruction or computer based training. Regardless of the format, training should be properly documented and documentation should be maintained and available for inspection. Also training should include both new and temporary staff and should ideally commence before they begin to perform their duties. Training will also be required for all newly issued SOP as well as revised SOPs.
GCP Training.

ICH GCP is a standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected.

ICH GCP states that it is the sponsor’s responsibility to ensure that studies are conducted and the data generated is to the protocol, GCP and the applicable regulatory requirements. Sites on the other hand, should be aware of GCP and comply with its standards and the applicable regulatory requirements.
Many clinical studies, whether or not they are intervention trials or observational studies, are required by insitutional or national requirements to be conducted to ICH-GCP.
The investigator and team, including the sub-investigator, clinical trial manager, research assistant, and all others involved in the planning and implementation of a clinical trial should understand and accept their roles and responsibilities as outlined not only in the applicable regulations but in GCP.

The sponsor is responsible for ensuring that investigators are qualified by experience and training and confirmation of all relevant experience and training is needed. Training includes good clinical practices and human subject protection; along with the study protocol and such documentation necessary to aid the teams understanding of the study. This does not mean that the sponsor is required to provide GCP training, because many programs are readily available either as classroom training or, more commonly, online training which can be accessed on behalf of the site or by individuals. The Global Health Network provides a free online course in ICH-GCP that can be found here (http://globalhealthtrials.tghn.org/elearning/other-resources/), and those scoring over 80% gain a certificate which can be maintained by the individual and/or site.

Sponsors should however have policies in place that ensure that the clinical teams are adequately trained and that the trainings are documented. GCP training could take place at the sponsor investigator’s meeting or kick off meeting of a clinical study. The advantage of this approach is that each study is able to show and document training just before commencing the study at no additional cost. Incorporating ICH-GCP training into study start or initiation meetings is very helpful because the GCP steps can be taught by way of example in terms of how the study has been designed and is to be operated. For example, the ICH-GCP section on informed consent can be explained and then the consent process specific to this study described. This makes the ICH-GCP step more relevant and supports the implementation of the consent process within the whole team. This can be done readily for many steps (such as adverse event reporting). This is a much more interesting way to deliver GCP training and is perfectly accetable.

There is no need for an outside group or agency to come in and teach ICH-GCP. Anyone with the appropriate experience can deliver it, including someone appropriately experienced from within the team. This indeed is very effective because it makes the training relevant and appropriate. ICH-GCP training certainly does not need to be expensive and should be accessible to all, whether online or via study start training.

The format for the training should also be thought through properly so that participants are engaged for majority of the training. Some methods of GCP delivery include having a quiz session or drawing out pertinent aspects of GCP that are relevant or specific sites’ responsibilities. Sites that are unable to attend can then be trained by the monitor at the site initiation visit.

Whilst GCP training ensures that basis ethical standards are met, training should be structured to include the local country’s law and regulations where the study is being conducted. In Europe, clinical trials are conducted to the European GCP directive, which supplements the Clinical Trials Directive, which strengthens the legal basis for Member States to comply with the principles and guidelines of good clinical practice.

It is recommended that researchers develop procedures and systems for trial management that meet the principles of GCP, and that these are clearly documented so that adherence can be readily demonstrated. GCP refresher courses should be encouraged, especially for those that have taken the course a long time ago. There is no provision in GCP as to how often refresher training should take place but some institutions will insist on a refresher course every 2 years, but this will depend on the institution’s requirements and their SOPs.

One key challenge of conducting GCP training is the fact that each sponsor may require sites to perform their structured GCP training prior to participating in their study. Sponsors should be flexible in their dealings with sites so that they don’t put off potentially viable sites.

Summary
It is important to clarify that GCP training is not the same as SOP training and vice versa. However they absolutely can be delivered together, and this can be highly beneficial because the two distinct topics used together offer a more robust and comprehensive method of emphasising both trainings.

In the rapidly changing clinical research environment, continuous vigilance is needed to ensure data integrity and that human subject are protected. The extra work invested at the outset in initial planning and preparation as well as continuous improvement process will increase the quality and efficiency of clinical trials.


References
- Ronkin Sheila “SOPs: A must for sites - Detailed instructions for creating strong SOPs that can serve as the backbone of studies and sites” Applied Clinical Trials Mar 2010 http://www.appliedclinicaltrialsonline.com/appliedclinicaltrials/article/articleDetail.jsp?id=660739&sk=&date=&pageID=2

- Kleppinger C.K and Ball L.K “Building Quality in Clinical Trials With Use of a Quality Systems Approach” Clin Infect Dis. (2010) 51 (Supplement 1): S111-S116

- Green J and stack J “The Case for Universal GCP Education” Applied Clinical trials Dec 2012
http://www.appliedclinicaltrialsonline.com/appliedclinicaltrials/article/articleDetail.jsp?id=800003&sk=&date=&%0A%09%09%09&pageID=2

- Zimmerman J “The Importance of Standard Operating Procedure for Investigator” Society of Clinical Research Associates 1999 http://www.impactcg.com/docs/SOCRA_11.99_SOPs.pdf