我国药物临床试验法规与相关国际法规的对比研究

文中通过比较我国药物临床试验法规与相关国际法规的差异,对两者之间存在的临床试验批准、临床试验机构选择、伦理委员会的设置、受试者损害补偿机制、不良事件监控体系和受试者招募广告6个方面的差异进行了分析,并针对上述差异提出了相关的建议,从而使我国的临床试验研究政策与国际接轨,提高我国药物临床研究的水平。     

Availability of post-trial access in clinical trials: a review of clinical trial protocols submitted to the research ethics board of the University of the Philippines Manila

Objectives: Ethics guidelines such as the Declaration of Helsinki and the CIOMS International Ethical Guidelines for Health-related Research Involving Humans require the sponsors, in cooperation with relevant stakeholders, to provide post-trial access (PTA) to intervention and knowledge, especially in clinical trials held in resource-poor regions. To date, we have very limited knowledge in terms of whether PTA is provided at all, and in what form. To partially address this current limitation, this study wished to explore whether, for which type of drugs and in what form PTA is provided in the Philippines.

Methods: We looked at all the clinical trial protocols submitted to the University of the Philippines Manila from 2012 to 2017. A total of 193 clinical trial protocols were included in the study. To identify whether, for which drug type and in what form PTA is provided, we gathered the following information: start and end date of the trial, name of study drug, tested indication of the study drug, region the sponsor is from, type/category of the study drug, type of funding agency, provisions for PTA (yes or no) and the explanation for the provisions. PTA provisions were further described according to the form in which PTA was provided and the types of drugs that were given PTA.

Results: Of the 193 protocols, 51.81% indicated PTA, though PTA in the form identified in guidelines can be partially accounted for in only 29.5% (57). The most common form of PTA is the provision or sharing of information (40). None of the protocols provided PTA in the form of access to intervention after the trials, with the possible exemption of 10 protocols that declared future evaluation of the sponsor for PTA depending on patient need, and another seven that might offer the option to transfer to an open-label extension study after the trial.

Conclusion: More work is needed if PTA, as stipulated in ethics guidelines, is to be reflected in reality.     

A sequential trial of pain killers in arthritis: issues of multiple comparisons with control and of interval-censored survival data

A large clinical comparison of pain killers used in the treatment of arthritis was conducted using a sequential design. The trial presented two major challenges: there were three treatments to be compared, and patients were assessed annually for up to 7 years. Treatment comparisons were made by selecting appropriate pairwise comparisons, to which standard theory could be applied. Rules concerning actions to take in the event of each stopping criterion being reached were evaluated by simulation. The annual assessments were used to create an interval-censored survival time: the year during which “disease progression” first occurred.     

The HORIZON Recurrent Fracture Trial: design of a clinical trial in the prevention of subsequent fractures after low trauma hip fracture repair

SUMMARY

Objective: To present the novel design of a trial testing the safety and efficacy of a yearly bisphosponate, zoledronic acid, in preventing new clinical fractures in patients with recent low trauma hip fracture repair.

Research design and methods: Randomized, placebo-controlled, triple-blind study. One hundred and fifteen clinical centers worldwide are recruiting approximately 1714 subjects aged 50?years and over (no upper age limit, median age of enrolled subjects to date 79?years) who have undergone surgical repair of a low trauma hip fracture in the preceding 90?days. Patients will be assigned at random to an intervention group (5?mg zoledronic acid intravenously yearly) or a control group (placebo infusion yearly). Both groups receive a loading dose of Vitamin D2 or D3 IM or orally, followed by 800–1200?IU Vitamin D and 1000–1500?mg elemental calcium orally on a daily basis. Concomitant therapy with calcitonin, hormone replacement therapy, selective estrogen receptor modulators, tibolone, and external hip protectors are allowed.

Main outcome measures: The primary endpoint is subsequent skeletal fractures as adjudicated by a clinical endpoints committee blinded to intervention status. Secondary outcomes include delayed hip fracture healing, changes in bone mineral density, and health resource utilization. Subjects will be recruited over a 3–4?year period and will be followed until 211 primary endpoints are accrued and adjudicated.

Conclusions: This randomized clinical trial is novel among osteoporosis therapies as it (1) targets hip fracture patients, a previously understudied group, and (2) uses only clinically evident fractures as the primary outcome. Ethical and practical considerations in studying this frail population are discussed.