The Human Medicines Regulations 2012

[F1 Format of the final study report U.K.

32.   The final study report for a non-interventional post-authorisation safety studies must be submitted in the following format—

(a) title, including a commonly used term indicating the study design; sub-titles with date of final report and name and affiliation of the main author;

(b) abstract, namely a stand-alone summary referred to in paragraph 31;

(c) name and address of the holder;

(d) investigators, namely the names, titles, degrees, addresses and affiliations of the principal investigator and all co-investigators, and list of all collaborating primary institutions and other relevant study sites;

(e) milestones, namely the dates for the following milestones—

(i) start of data collection (planned and actual dates),

(ii) end of data collection (planned and actual dates),

(iii) study progress reports,

(iv) interim reports of study results, where applicable,

(v) final report of study results (planned and actual date), and

(vi) any other important milestone applicable to the study, including date of study registration in the electronic study register

(f) rationale and background, namely a description of the safety concerns that led to the study being initiated, and critical review of relevant published and unpublished data evaluating pertinent information and gaps in knowledge that the study is intended to fill;

(g) research question and objectives;

(h) amendments and updates to the protocol, namely a list of any substantial amendments and updates to the initial study protocol after the start of data collection, including a justification for each amendment or update;

(i) research methods, namely—

(i) study design: key elements of the study design and rationale for this choice,

(ii) setting: setting, locations, and relevant dates for the study, including periods of recruitment, follow-up, and data collection: in the case of a systematic review or meta-analysis, study characteristics used as criteria for eligibility, with rationale,

(iii) subjects: any source population and eligibility criteria for study subjects. Sources and methods for selection of participants shall be provided, including, where relevant, methods for case ascertainment, as well as number of and reasons for dropouts,

(iv) variables: all outcomes, exposures, predictors, potential confounders, and effect modifiers, including operational definitions: diagnostic criteria shall be provided, where applicable,

(v) data sources and measurement: for each variable of interest, sources of data and details of methods of assessment and measurement; if the study has used an existing data source, such as electronic health records, any information on the validity of the recording and coding of the data must be reported and in the case of a systematic review or meta-analysis, description of all information sources, search strategy, methods for selecting studies, methods of data extraction and any processes for obtaining or confirming data from investigators,

(vi) bias,

(vii) study size: study size, rationale for any study size calculation and any method for attaining projected study size,

(viii) data transformation: transformations, calculations or operations on the data, including how quantitative data were handled in the analyses and which groupings were chosen and why,

(ix) statistical methods: description of the following items—

(aa) main summary measures,

(bb) all statistical methods applied to the study,

(cc) any methods used to examine subgroups and interactions,

(dd) how missing data were addressed,

(ee) any sensitivity analyses, and

(ff) any amendment to the plan of data analysis included in the study protocol, with rationale for the change, and

(x) quality control: mechanisms to ensure data quality and integrity;

(j) results: comprising the following subsections—

(i) participants, namely numbers of study subjects at each stage of study: in the case of a systematic review or meta-analysis, number of studies screened, assessed for eligibility and included in the review with reasons for exclusion at each stage,

(ii) descriptive data: characteristics of study participants, information on exposures and potential confounders and number of participants with missing data. In the case of a systematic review or meta-analysis, characteristics of each study from which data were extracted,

(iii) outcome data: numbers of study subjects across categories of main outcomes,

(iv) main result: unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision and where relevant, estimates of relative risk must be translated into absolute risk for a meaningful time period,

(v) other analyses, and

(vi) adverse events and adverse reactions;

(k) discussion which must include—

(i) key results with reference to the study objectives, prior research in support of and conflicting with the findings of the completed post-authorisation safety study, and, where relevant, the impact of the results on the risk–benefit balance of the product,

(ii) limitations of the study taking into account circumstances that may have affected the quality or integrity of the data, limitations of the study approach and methods used to address them, sources of potential bias and imprecision, and validation of the events; both the direction and magnitude of potential biases must be discussed,

(iii) interpretation of results, considering objectives, limitations, multiplicity of analyses, results from similar studies and other relevant evidence, and

(iv) generalisability; and

(l) references.]

Textual Amendments

F1 Sch. 12A inserted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), reg. 1, Sch. 6 (as amended by S.I. 2019/1385, reg. 1, Sch. 1 para. 9 and S.I. 2020/1488, reg. 1, Sch. 2 para. 192); 2020 c. 1, Sch. 5 para. 1(1)