Regulatory

Regulatory

Study Design

PMW offers consultancy for all stages of study design, including investigators and experts’ engagement, biostatistician input and preparation of effective study protocol.

Our scientific and industry experience results in shorten planning phase, successful submission to authorities, and efficiently designed study with optimal number of patients. Please do not hesitate to contact us for a preliminary estimate.

Documentation of clinical trials

PMW prepares, edits and translates:

  • study protocol
  • investigator brochure (IB)
  • electronic case report form (eCRF)
  • patient informed consent form
  • narratives
  • statistical analysis plan (SAP)
  • statistical report
  • periodic safety update report (PSUR)
  • development safety update report (DSUR)
  • interim analysis report
  • clinical study report (CSR)

Documentation of clinical studies submitted to regulatory agencies in Poland (URPL, The Office for Registration of Medicinal Products), and elsewhere (EMA, Food and Drug Administration [FDA]), and to bioethics committees are prepared according to URPL, EMA i FDA requirements.

Following EMA recent initiative (as of October 20, 2016) on granting open access to clinical reports for new medicines for human use authorised in the European Union (EU), we prepare, according to EMA guidelines, the redacted CSR to be published at EMA website.

Observational studies & registries

Moreover, the interactive solutions we offer enable close co-operation between investigators and sponsors, and they facilitate the day-to-day clinical care of the patient (patient management tools). Please do not hesitate to contact us for a free preliminary estimate.

Moreover, the interactive solutions we offer enable close co-operation between investigators and sponsors, and they facilitate the day-to-day clinical care of the patient (patient management tools). Please do not hesitate to contact us for a preliminary estimate.

1 ICH - GCP: International Conference on Harmonisation – Guideline for Good Clinical Practice

Patient-reported outcomes

We translate and validate patient-reported outcome (PRO) forms, including quality of life (QoL) questionnaires, from English into Polish. The Polish versions of QoL questionnaires are prepared using double translation (forward and backward), according to the guidelines of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR)1. Alternatively, we use dual translation panels 2. We also create original PRO forms, and offer validation of newly devised ones. We provide patient feedback questionnaires for:

  • quality of life
  • treatment and health care satisfaction
  • symptom and complaint assessment
  • personal, professional, and social functioning
  • general health

The PRO forms we prepare may be used (also electronically) in multicentre clinical trials (with centres using different operational languages), observational studies, patient registries, and day-to-day medical practice. At the same time, we can provide advice on the selection of an appropriate questionnaire for a planned clinical study, or supervise the process of creating a new form. Please do not hesitate to contact us for a free preliminary estimate.

1 Principles of Good Practice for the Translation and Cultural A daptation Process for Patient-Reported Outcomes (PRO) Measures: Report of the ISPOR Task Force for Translation and Cultural Ad aptation, Value in Health, 2005;8(2):95-104 2 Swaine-Verdier A, Doward LC, Hagell P, et al. Adapting quality of life instruments, Value in Health, 2004;7(suppl. 1):s27–s30

Biostatistics

All our statisticians have a strong educational background in mathematics with a specialization in statistics, and are experienced in collaborating with physicians and scientists on designing the study and analyzing the results. Thanks to their many years of experience in cooperating with the medical and pharmaceutical community, they can perfectly understand the problems faced by the researcher at any stage of the research work.

We provide statistical analyses of your data, and also calculations of sample size for your study. We also advice on the design of your study from the statistical point of view, on the use of correct statistical tests and help in the interpretation of the data. We can help you identify the most important elements of your data, and choose the best way to present them - a task that can be confusing and difficult.

We offer a complete package, from study design and writing statistical analysis plan, through data analysis and writing the protocol to writing the clinical study report (CSR).

All services are compliant with GCP.

Please do not hesitate to contact us for a preliminary estimate.

CE mark & FDA regulatory support

As defined in Directive 93/43/EEC, a medical device is:

“Any instrument, apparatus, appliance, software, material or other article, whether used alone or in combination, including the software intended by its manufacturer to be used specifically for diagnostic and/or therapeutic purposes and necessary for its proper application, intended by the manufacturer to be used for human beings for the purpose of:

  • diagnosis, prevention, monitoring, treatment or alleviation of disease,
  • diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap,
  • investigation, replacement or modification of the anatomy or of a physiological process,
  • control of conception,

and which does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means".

The decision as to whether a product is classified as a medical device is generally made by the manufacturer on the basis of its intended use. However, the national competent authorities may still refuse to register the product as a medical device. Therefore, it is important to consider how the product has been classified in other EU countries.

If the product complies with all the requirements of the European Commission's product class directives, the manufacturer may include a CE mark on the product. CE-marking confirms passage of the conformity assessment procedure, and means the product can be sold or marketed throughout the European Union.

For some products, such as medical devices, it is necessary to meet the requirements of more than one directive or to pass the assessment of an independent body (notified body). In particular, medical devices may be subject to the following directives:

In Poland, the provisions of Directive 93/42/EEC (as well as Directives 90/385/EEC and 98/79/EC) are implemented through the Medical Devices Act of 20 May 2010, along with 12 related regulations of the Minister of Health.

To obtain a CE mark, manufacturers must:

  • assess whether the product is a medical device according to Medical Device Directive (93/42/EEC)
  • classify the product
  • choose the optimal path for the company and product conformity assessment
  • implement a quality management system (optional), and procedures for post-production supervision, incident reporting, and document storage
  • identify the essential requirements for the product and the harmonized standards
  • implement the requirements of these standards or assess the safety and effectiveness of the declared function in accordance with the harmonized standards and the current knowledge
  • perform risk analysis and clinical evaluation, and then make the necessary corrections
  • develop a checklist for meeting the essential requirements
  • apply for certification by a notified body (optional)
  • issue a declaration of conformity and report the product to the registry.

Proper Medical Writing (PMW) provides comprehensive services for each of the above stages of applying for CE, in accordance with Art. 58 of the Medical Device Act.

We also offer consultations on any US FDA proceedings.

Clinical evaluation

According to the MEDDEV 2.7/1 revision 4 (Clinical Evaluation: a guide for manufacturers and notified bodies under Directives 93/42/EEC and 90/385/EEC), published by EMA in June 2016, clinical evaluation is defined as:

“a methodologically sound ongoing procedure to collect, appraise and analyse clinical data pertaining to a medical device and to evaluate whether there is sufficient clinical evidence to confirm compliance with relevant essential requirements for safety and performance when using the device according to the manufacturer’s Instructions for Use.”

The evaluation is based on comprehensive analysis of clinical data relevant to the intended use. The process is documented in a clinical evaluation report (CER). Upon completion, the document is reviewed to verify if there is sufficient evidence to meet the relevant Essential Requirements set out in the EU Medical Device Directive (93/42/EEC).

Clinical evaluation is an ongoing process that occurs throughout the life cycle of a medical device.

Proper Medical Writing (PMW) has expertise to assist at each step of this process, including the preparation of CERs required for initial CE-marking and subsequent updates. PMW will prepare CERs according to EMA and national regulatory authority requirements in a timely and accurate manner.

To obtain an individual quote, please do not hesitate to contact us.

Investigational medicinal product dossier

The Investigational Medicinal Product Dossier (IMPD) is one of several documents required whenever the performance of a clinical trial is intended in the EU. According to the EU Directive 2001/20 (“clinical trials directive”) sponsors must submit the following to a competent authority:

  • Description of the quality and manufacture of the investigational medicinal product
  • Any toxicological and pharmacological tests
  • The Clinical Study Protocol
  • Clinical information on the investigational medicinal product (IMP), including Investigator's Brochure.

Guidance on structure and content of an IMPD is provided in the ENTR/CT1 Guidance (REV2). The IMPD includes summaries of information related to the quality, manufacture and control of any IMP (including reference product and placebo), and data from non-clinical and clinical studies. In general, the IMPD contains four main sections: quality data; non-clinical pharmacology and toxicology data; previous clinical trial and human experience data; and the overall risk /benefit assessment.

Quality data should be reported according the EU Guideline on IMPs in clinical trials (CHMP/QWP/185401/2004). Non-clinical pharmacology and toxicology data should document pharmacodynamics, pharmacokinetics, toxicology, genotoxicity, carcinogenicity, local tolerance and phototoxicity in accordance with ICH S7A, CPMP/ICH/286/95, ICH S2A, CPMP/ICH/140/95, CPMP/ICH/141/95, CPMP/SWP/2145/00, CPMP/SWP/398/01. In first-in-human trials, when no clinical data are available, the IMPD may summarise the clinical data of related drugs.

While regulatory requirements for Marketing Authorisation Applications are well defined, requirements for clinical trials are less clear and more flexible. In addition, the size and content of IMPDs may evolve as a drug develops. The European harmonisation process is also still ongoing. If you are unsure about how to write an IMPD, please do not hesitate to contact us.

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